Human parechoviruses (HPeVs) are newly recognized single-stranded RNA viruses that were formerly classified in the Enterovirus genus1). Among 16 HPeV serotypes, HPeV-3 infection occurs most frequently among infants below the age of 3 months2). Since HPeV-3 was first isolated in Japan in 19991), the HPeV serotype has been increasingly identified as an important pathogen of sepsis-like illness and central nervous system infections in neonates and young infants3). Life-threatening illnesses such as hemophagocytic lymphohistiocytosis have been reported in neonatal HPeV-3 infection4). However, the major clinical features displayed by patients with HPeV-3 infection are also common in those suffering from severe infectious diseases caused by other pathogens5). Thus, the diagnosis of HPeV-3 infection is difficult based only on clinical signs.

Recent studies have reported several clinical findings that are characteristic of HPeV-3 infection4678). Clinical features such as palmar-plantar erythema and hyperferritinemia might be diagnostic indicators of an HPeV3 infection in febrile neonates and young infants67). This report describes 2 young infants with an HPeV3 infection who presented with a prolonged fever, palmar-plantar erythema, and hyperferritinemia (>500 ng/mL). These cases may enhance our understanding of the unique features of HPeV-3 infection in young infants.

In the recipients of allo-HSCT, the difference in the reported incidence is due in part to asymptomatic or subclinical manifestations in most of viral infections and the changing epidemiology of viruses as well as differences in diagnostic methods. Till now, large-sampled epidemiological data on overall incidence of viral infections are absent in the recipients of allo-HSCT. The limited data show that community acquired respiratory viruses (CARVs) and herpesviruses are the most common pathogens. Among the causes of CARVs respiratory tract infections, a preponderance of respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are reported, followed by influenza virus and human metapneumovirus (HMPV). In herpesvirus family, the incidence of herpes simplex virus (HSV) and varicella zoster virus (VZV) infections as well as cytomegalovirus (CMV) diseases have significantly decreased because of the effective prophylaxis. The reports on human herpes virus (HHV)-6 diseases are increasing in allo-HSCT recipients.

In the recipients of allo-HSCT, most viral infections are opportunistic and closely related with immune status. Thus, factors influencing engraftment and immune reconstitution all potentially impact viral infections. Peripheral blood stem cell transplantation is associated with fewer viral infections than bone marrow and cord blood transplantation due to better hematopoietic and immune reconstitution. Compared with HLA-match related transplantation, HLA-mismatch related and unrelated transplantation have an increasing risk of viral infections because immune reconstitution is delayed by the intensified GVHD prophylactic strategy, such as the use of ATG. GVHD may delay immune reconstitution and is considered an independent risk factor of viral infections. In addition, other factors, such as the serologic status of donors and recipients before transplantation as well as the age of recipients, may also affect the incidence of viral infections. For example, CMV-seronegative recipients receiving graft from CMV-seropositive donors are at high risk of CMV diseases. Children are high-risk population of CARVs infections.

Herpesviridae is a family of viruses with double-stranded DNA. The B virus (Cercopithecine herpesvirus 1, or herpes B virus) and Cercopithecine herpesvirus 2 (CeHV-2) are primate herpes viruses that belong to the alpha-herpesvirus subfamily, and are closely related to herpes simplex virus 1 (HSV-1). The coated particle harbors a linear double-stranded DNA genome of about 157 kb (1-4). Herpes B virus (BV) is a zoonotic virus and its natural host is mainly cercopithecidae, although BV infections are usually mild or unapparent in macaques, yet lead to fatal encephalitis and encephalomyelitis in humans (2, 5, 6). Previous studies (7) have shown that BV is the only known agent that could infect humans among the 35 herpesviruses confirmed in nonhuman primates. In the early stages of infection, if not treated by antiviral therapy, the infection would have a high mortality.

As nonhuman primates are the main experimental animals for biomedical research, development of an effective method for surveillance of BV infection is essential for the establishment of BV-free monkey colonies and reduction of the risk for laboratory workers, animal handlers and researchers (8). Unfortunately, in most cases, usage of cell culture or polymerase chain reaction (PCR) for an immediate diagnosis of BV infection was impossible, for the existence of similarity between BV and other alphaherpesviruses. Herpes B virus spends a life-long lurking in sensory ganglia of macaques and rarely reactivates (9). The detection of serum antibodies to BV proteins was used for diagnosis of BV infections in humans and monkeys. Thus, serological test of anti-BV antibodies is the only effective way for the surveillance of infected animals.

Currently, a few serological test techniques are being used to detect the viral infection, relying on recombinant proteins and cell lysates of BV (10). To identify infected animals, the solubilized HSV-infected cell antigen was developed and used for ELISA and other rapid serological tests (11-13), with subsequent western-blotting confirmation to identify specific targets that could be immunoreactive with serum antibodies (14). Because of high cross-reactivity with BV proteins, HSV type 1 (HSV-1) and HSV-2 are not specific enough to clearly identify BV infections in herpes simplex virus (HSV) positive humans by this method (15, 16). Among the twelve glycoproteins, which contained in the viral envelope, four had proven with high immunogenicity, gB, gD, gC and mgG (3, 10, 17), the primary targets of IgG antibody responses of the in patients, who were infected by the HSV-1 or HSV-2 have been confirmed as the nucleocapsid complex p40, and the major capsid protein VP5 (6, 16, 18-20), it would be a complex task to differentiate them.

Most importantly, BV is a biosafety level 4 (BSL-was similar with glycoprotein D of HSV-1 and4) pathogen; currently BV-infected cell lysates are used as a diagnostic antigen in serological tests and only maximum containment laboratories (BSL-4) have the qualification to produce it, this requirement limits the amount of facilities, which provide the antigen. When compromising outcome measures based on assays using these antigens, the antigens may also suffer from lot-to-lot variation. The glycoprotein D (gD) of BV is a 35-kDa glycoprotein identified in the BV envelope and is among the main surface antigens shown to elicit antibodies in sera of infected animals.

It has a high homology with HSV-1; its amino acid sequence is 56% - 58% identical to that of HSV-1 gD (1). Moreover, BV gD was similar with glycoprotein D of HSV-1 and HSV-2, and is one of the immunodominant envelope proteins that can elicit humoral and cellular immunity in animals and human individuals; the gD protein has been considered as a good immunogen (6, 21). Finally, BV gD protein could bind to human nectin-1 receptors for cell-cell fusion and virus entry (22, 23). Therefore, in B virus infection the gD has been identified as a multifunctional protein, and production of mAbs against gD could also provide an effective tool for elucidation of the exact function of BV glycoprotein gD.

Viruses are ubiquitous in the environment and are the most common source of infection among immunocompetent individuals. Despite their pervasiveness, viral infections are generally not considered to be of clinical significance among the critically ill, unless the patient is significantly immuncompromised. Much is known about the progression of viral infections as opportunistic pathogens among immunocompromised patients while little is known about their role in patients who are immunocompetent before hospitalization. Even among patients with no history of immunosuppression, reactivation of viral herpes viruses (cytomegalovirus (CMV) and herpes simplex virus (HSV)) has been documented in critically ill–[10]. This suggests that at least for some critically ill patients with no pre-hospital diagnosis of immunosuppression, newly acquired or reactivation of viral infections during hospitalization can be clinically significant in this patient population.

Using a large population based database, we sought to examine the association of viral infections to the outcomes of ICU patients with no evidence of infection or immunosuppression on admission, and to identify potential variables amenable to intervention. We hypothesize that acquired viral infections during hospitalization may carry their own risk for adverse outcomes among patients in the intensive care unit.

A 42-day-old male neonate was admitted to Gyeongsang National University of Hospital due to high fever and irritability. He was born at full-term gestational age at a weight of 3,200 g, and he was thriving until this hospital visit. Localized symptoms were not detected, and the results of a physical examination were unremarkable. His healthy older sister was reported to have had a recent febrile respiratory infection. The patient's initial vital signs were as follows: blood pressure 80/50 mmHg, heart rate 168 beats/min, respiratory rate 38 breaths/min, and body temperature 38.8℃. The laboratory findings at admission were as follows: hemoglobin, 9.0 g/dL; white blood cell (WBC) count, 1,990/mm3; absolute neutrophil count, 670/mm3; platelet count, 390×103/mm3; aspartate aminotransferase (AST), 42 U/L (range, 22–63 U/L); alanine aminotransferase (ALT), 23 U/L (range, 12–45 U/L); γ-glutamyl transferase (γ-GT), 36 U/L (range, 12–123); creatine kinase (CK), 147 U/L (range, 5–130 U/L); lactate dehydrogenase (LDH), 283 U/L (range, 170–580 U/L); ferritin, 385 ng/mL (range, 0–400 ng/mL); protein, 5.5 g/dL (range, 4.6–7.4 g/dL); albumin, 4.0 g/dL (range, 1.9–5.0 g/dL); and C-reactive protein (CRP), 0.5 mg/L (range, <7.9 mg/L). No cerebrospinal fluid (CSF) pleocytosis or pyuria was observed. Cefotaxime and ampicillin/sulbactam were administered.

No bacteria were found in blood, CSF, or urine samples. HPeV-3 was detected in CSF and serum samples by reverse transcription polymerase chain reaction (PCR) as described in our previous study9). CSF PCR tests were negative for herpes, enterovirus, cytomegalovirus, Epstein-Barr virus, and HPeV1. In addition, we found no respiratory viruses such as adenovirus, coronavirus, parainfluenza virus, rhinovirus, respiratory syncytial virus, influenza virus, bocavirus, and metapneumovirus. High fever and irritability persisted. At day 5 of admission, an erythematous rash and swelling were observed on the patient's hands and feet. The laboratory findings were as follows: hemoglobin, 8.7 g/dL; WBC count, 3,930/mm3; absolute neutrophil count, 260/mm3; platelet count, 160×103/mm3; protein, 4.4 g/dL; albumin, 2.9 g/dL; AST, 658 U/L; ALT, 162 U/L; γ-GT, 147 U/L; CK, 321 U/L; LDH, 1,324 U/L; ferritin, 2,581 ng/dL; and CRP, 0.3 mg/dL. Intravenous immunoglobulin (IVIG) was administrated because severe systemic inflammatory responses were considered in the patient. After IVIG treatment, the patient's fever subsided gradually and the erythematous rash disappeared. The patient was discharged on day 8 of admission.

A population based retrospective cohort study using the University HealthSystem Consortium (UHC) Database, specifically searching the Resource Manager and Clinical Database within the UHC system, was conducted. The UHC is comprised of 103 academic institutions and 210 affiliate institutions representing over 90% of all academic medical centers in the United States. The UHC database is an administrative database, comprised of International Classification of Disease-9 (ICD-9) diagnosis and procedure codes. At present, it is the only population based dataset to contain information on the critically ill and their exposure to viral and bacterial infections.

Only patients without a diagnosis of infection present on admission were included in the study. The inclusion criteria included immunocompetent ICU patients greater than or equal to eighteen years of age admitted to the hospital between the third quarter, 2006, and second quarter, 2009. Patients with a primary or secondary ICD 9 code signifying a history of organ transplantation, human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), autoimmune disease, leukemia, pancytopenia, or lymphoma were excluded. Immunocompetency was defined as the absence of the aforementioned diagnoses. A total 209,695 patients met the study criteria.

The search for an effective human immunodeficiency virus (HIV) vaccine has spanned over 30 years with hundreds of billions of dollars spent with no success. The repeated standard textbook explanation for this mystery is that because of the retroviral nature of HIV, its replication involves an error-prone reverse RNA to DNA transcription, making HIV vulnerable to mutation and thereby providing more means for escaping the host immune system. While there is likely some truth to this, a closer look at all available data reveals that such an explanation is limited as there are several counterexamples for this hypothesis. For instance, if this would be the case for all retroviruses that utilize the error-prone reverse transcription as the definition of retrovirus entails, why then effective vaccines have been found for HIV’s horse cousin, equine infectious anemia virus (EIAV), at least since 1973?. Furthermore, it should be noted that HIV is not the only virus, for which an effective vaccine is yet to be found despite enormous efforts. The hepatitis C virus (HCV) and herpes simplex virus-2 (HSV-2) are such examples, and, incidentally, these are not retroviruses, which seem to contradict the aforementioned textbook dogma. In fact, HCV and HSV-2 are single-stranded RNA and double-stranded linear DNA viruses, respectively. It would seem strangely coincidental that HIV, HCV, and HSV-2 all have strong sexual transmission components. The connection between sexual transmission and the unavailability of an effective vaccine is something that has never been and simply cannot be explained by the current textbook paradigm.

Given the serious deficiencies of the current textbook paradigm, it is clear that a mystery has been quietly plaguing the biomedical community for over three decades, and a new explanatory framework that could adequately address the aforementioned puzzles is much needed. This paper describes the concept of viral shell disorder or shapeshifting that was first introduced by us in a 2008 study that reported a strange characteristic not previously noticed in the outer shell and matrix of the HIV-1, namely the HIV-1 matrix was found to be highly disordered. In fact, using advanced computational techniques (e.g., PONDR®-VLXT) we showed that depending on a strain, the percentage of intrinsic disorder (PID) in HIV-1 matrix protein (p17) can be as high as 70%, the levels, which are very rare in the outer shells of other viruses. A decade has passed since the publication of that paper, and plenty of both computational and experimental data have been made available. For instance, we now know that the basis of its theoretical framework can be found in the 1920s classical experiments of Oswald T. Avery and Walther F. Goebel, who showed that bacterial polysaccharides are essentially ineffective as vaccines, but may become efficient being held together as a rigid conjugate with proteins. Furthermore, a shell disorder database of over 300 viruses and strains has been built with much of its data made publicly available. With the availability of information for a wide variety of viruses that include polio, rabies, HCV, HSV, and yellow fever viruses (YFV) important comparisons become feasible as we shall see below.

In the article titled “A Rare Cause of Childhood Cerebellitis-Influenza Infection: A Case Report and Systematic Review of Literature”, Dr. Candan Çiçek was missing from the authors' list. The corrected authors' list is shown above.

Additionally, there were errors in the Case Representation section which should be corrected as follows:“CSF cultures were bacteriologically sterile. Polymerase chain reaction [PCR] assays of CSF for influenza virus, herpes simplex virus 1 and 2, adenovirus, enterovirus, cytomegalovirus, human herpesvirus- 6, epstein-barr virus, and varicella zoster virus were all negative” should be corrected to “Multiplex polymerase chain reaction [PCR] assays of CSF for herpes simplex virus 1 and 2, adenovirus, enterovirus, cytomegalovirus, human herpesvirus-6 and -7, Epstein-Barr virus, varicella zoster virus, parechovirus, parvovirus B19 (Neuro 9 Detection, Fast Track Diagnostic, Malta) and influenza virus type A and B, parainfluenza virus, adenovirus, respiratory syncytial virus, human metapneumovirus, human bocavirus, human coronavirus, enterovirus, and rhinovirus (Allplex Respiratory Panel Assays, Seegene, South Korea) were all negative.”“Serologic tests of his blood showed negative results for epstein-barr virus, herpes simplex virus, varicella-zoster virus, cytomegalovirus, measles, mumps, rubella, and mycoplasma pneumoniae. Respiratory viruses such as adenovirus, rhinovirus, respiratory syncytial virus, parainfluenza virus, human bocavirus, human metapneumovirus, and coronavirus were not detected in the nasopharyngeal swab specimen by multiplex PCR. However, we identified influenza A H1N1 virus on the third day of the onset of the symptoms, which was when we started treatment with oseltamivir as 4 mg/kg orally twice a day. The patient was diagnosed with influenza-associated cerebellitis based on the clinical findings” should be corrected to “Serologic tests of his blood showed negative results for Epstein-Barr virus, herpes simplex virus, varicella zoster virus, cytomegalovirus (Vidas®, bioMerieux, France), measles, mumps, rubella, and mycoplasma pneumoniae (Diesse Chorus ELISA, Italy). Respiratory viruses including adenovirus, rhinovirus, respiratory syncytial virus, parainfluenza virus, human bocavirus, human metapneumovirus, and coronavirus were not detected in the nasopharyngeal swab specimen by multiplex PCR (Allplex Respiratory Panel Assays, Seegene, South Korea).”

Viral neonatal and paediatric infections are characterised by a great heterogeneity of clinical manifestations and are considered as major causes of neonatal and paediatric morbidity and mortality (1). Almost 50 years ago, Paediatric Virology was not considered an isolated discipline and was included in the Paediatric Infectious Diseases section of the scientific field of Paediatrics (2,3). However, during the past two decades, new advances in the field of Clinical Virology and Molecular Medicine have expanded the level of knowledge on the prevention, diagnosis and treatment of viral infections occurring in infancy and childhood (4,5). These developments and changes highlight the demand for undergraduate and postgraduate medical education in Paediatric Virology, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence-based Medicine, Clinical Governance, Quality Improvement, and Pharmacology and Immunology (5).

The 3rd Workshop on Paediatric Virology was entitled ‘Paediatric Virology: Interaction between basic science and clinical practice’. It was held on October 7th, 2017 in Athens, Greece, as an official session of the 22nd World Congress on Advances in Oncology and the 20th International Symposium on Molecular Medicine. Its aim was to bring together virologists and paediatric health professionals and encourage them to collaborate as an international network to promote paediatric health. Moreover, during the workshop, Nobelist laureate Professor Harald zur Hausen, Emeritus Professor of Virology at the University of Freiburg in Germany, who received the 2008 Nobel Prize in Physiology or Medicine for his discovery of human papilloma viruses (HPVs) causing cervical cancer and Professor Anne Greenough, Professor of Neonatology and Clinical Respiratory Physiology at King’s College London, UK and Vice President of Science and Research at the Royal College of Paediatrics and Child Health (RCPCH), were honoured by the Paediatric Virology Study Group (PVSG) for their indisputable academic, research and publishing contribution to Paediatric Virology.

The present review provides an overview on the wealth of new material from different areas of neonatal and paediatric viral infections presented and discussed during the workshop. Interestingly, 7 out of the 10 top key messages (Table I) of our meeting, as well as both statements of Nobelist laureate Professor Harald zur Hausen, on the occasion of this workshop (Table II), included recommendations on specific prevention strategies against viral infections. Along with the significant role of human breast milk and respiratory syncytial virus (RSV) prophylaxis, these issues included the necessity of the vaccination policy in relation to the migration crisis, prevention of hepatitis in newborns, recent advances on influenza vaccines, male vaccination against HPVs and the the preventative role of probiotics in the management of viral infections in children.

The prevalence of viral diseases has increased due to the availability of modern diagnostic tests that allow rapid detection of viruses. Viral diseases may additionally be associated with significant morbidity and mortality as is the case with some emerging viral diseases, such as the Middle East Respiratory Syndrome coronavirus or avian influenza [2, 3]. Patients with severe viral infections are often hospitalized in intensive care units (ICUs); on the other hand recent studies have underlined the frequency of virus detection in ICU patients [4–6]. The majority of viral infections that require ICU care involve the respiratory tract or the central nervous system. However, other organ systems, such as the gastrointestinal tract, may be severely affected by viruses and require support or close monitoring. The reported incidence of viral infections reported in the ICU varies widely across studies and geographic regions and has changed over the recent years based on the epidemiology of emerging viral infections such as human metapneumovirus and adenovirus infections [7, 8]. Improved molecular detections methods have also significantly changed the epidemiology of viral infections in the ICU over the last years. Multi-institutional databases and time-series models may be useful tools to characterize and forecast the burden of severe viral infections at the local and institutional levels [9, 10]. Clinical signs and symptoms are rarely sufficient to make a specific diagnosis of a viral infection. Often a combination of the appropriate clinical syndrome together with epidemiologic clues but more importantly specific laboratory tests is used to reach the diagnosis. Viral infections can cause severe morbidity and mortality in certain hosts such as immunocompromised patients (Table 1) [12–52]. Herein, we review the literature on the role of viruses in ICU in adults [excluding Human Immunodeficiency Virus (HIV)] with a focus on treatment of these infections.

The constitutional symptoms and clinical features of viral sepsis are frequently indistinguishable from bacterial or fungal sepsis. Presenting symptoms and signs include fever, chills, rash, respiratory distress, nausea, vomiting, diarrhea, dysuria, confusion, and altered mental status. None of these symptoms is pathognomonic of sepsis, let alone viral induced sepsis. Moreover, classic features of systemic inflammation might not be seen in every individual, especially in immunocompromised children. Fever is one of the most common symptoms seen in septic children, attributable to the pyrogenic activity of IL-1, IL-6, IFNs, and TNF-α. It has been observed that these substances increase prostaglandin E2 synthesis in the hypothalamus (73, 74), resulting in the elevation in the host central nervous system core temperature set-point regulated by the pre-optic and dorsomedial hypothalamic nuclei (75). Hypothermia, on the other hand, is a less frequent but more specific indicator of sepsis that may be predictive of illness severity and death, especially in younger children and chronically debilitated patients (74). Injury to the vascular endothelium may result in broad array of failing organs that manifests as confusion, nausea, vomiting, diarrhea, oliguria, and coagulopathy. A myriad of cardiopulmonary manifestations ranging from mild tachypnea and tachycardia to acute respiratory distress syndrome and shock can be seen (76). The presenting symptoms usually depend on the type of virus. Clinical presentation in patients with respiratory viral infections can range from completely asymptomatic to severe respiratory distress due to pneumonia. Diarrheal illness has been observed in patients infected with rotavirus, norovirus, enterovirus, and adenovirus. VZV and HSV infection may present with vesicular rash. Children with HSV or arbovirus infection may have confusion, altered mental status or seizures from encephalitis. Elevated transaminases are common with HSV and enteroviral infections which may be complicated by hepatitis, coagulopathy and encephalitis. Neonatal HPeV infection can mimic other enteroviral infections in the initial presentation. Often these patients present with fever, rash, irritability, feeding intolerance, and seizures (17). They can develop sepsis like illness and encephalitis. Patients with acute HIV infection often have flu-like symptoms such as fever, headache and rash, which usually resolve spontaneously. These patients soon enter a phase of clinical latency until they develop acquired immunodeficiency syndrome, usually heralded by acquisition of an opportunistic infection.

As with other types of sepsis, virus-induced sepsis requires a high index of suspicion, especially in very young children and those with chronic medical conditions. Neonates and young infants are at higher risk of sepsis from HSV, HPeVs, and enterovirus. HSV is usually acquired perinatally from mothers with genital herpes. Mothers with primary herpes are more likely to transmit the infection when compared to those with recurrent and non-primary herpes (77). Nielsen et al reported that second born children are at higher risk of HPeV-3 infection than the firstborn (78). Seizures, drowsiness and lethargy, and absence of oral lesions are associated with severe enteroviral infection in children (79). In RSV infection, comorbid conditions reported to increase the risk for severe infection include the history of prematurity, congenital heart disease, chronic lung disease, and immunodeficiency (13). In a recent study, Eggleston et al found that patients with metapneumovirus infection were more likely to be older and have congenital heart disease compared to RSV infected patients (80). In contrast, asthmatics and premature infants were at higher risk for rhinovirus infection (81). Finally, predisposing conditions for severe pediatric influenza infection include age less than 2 years; asthma; cardiac, renal, hepatic, hematologic, neurologic or neuromuscular conditions; long-term aspirin therapy; immunosuppressive therapy and residence in a chronic care facility (82). Risk of mother-to-child perinatal HIV transmission is higher in mothers with CD4 count < 200 cells/μL and lower in infants receiving antiretroviral prophylaxis (83, 84). If patients with any of these conditions present with sepsis, diagnostic viral testing and appropriate empiric antiviral treatment should be strongly considered according to the individual's risk factors.

In recent years, viruses have been identified as an increasingly frequent cause of community-acquired pneumonia (CAP), because of the availability of new diagnostic tools, such as Polymerase Chain Reaction (PCR). On the other hand the emergence of the pandemic influenza virus in 2009 as well as the emergence of viruses with pandemic potential such as the avian influenza viruses or new coronaviruses has emphasized the role of viruses in severe community acquired pneumonia in places where these viruses are endemic. Viral nosocomial pneumonia [hospital-acquired, healthcare-associated pneumonia (HCAP) or ventilator-associated pneumonia (VAP)] have been described but the pathogenicity and the roles of viruses recovered from the lower respiratory tract in patients with pneumonia remains controversial. Severe viral infections such as influenza, severe acute respiratory syndrome (SARS) may cause respiratory failure which may rapidly progress to acute respiratory distress syndrome (ARDS) and multi-organ failure [55–58]. Except for pneumonia, acute respiratory failure can occur in patients with chronic obstructive pulmonary disease (COPD) and lead to hospitalization and the need for mechanical ventilation [55–58]. In addition, viruses can cause ARDS and neurogenic respiratory failure (for example through development of Guillain-Barré Syndrome) [55–58].

Viruses are the smallest among all self-replicating organisms and yet they are the etiological agents of many difficult to treat diseases in human populations. There are broad types of human infections caused by viruses, such as respiratory infections (common cold, Influenza), digestive infections (viral gastroenteritis), central nervous system infections (viral meningitis, viral encephalitis), skin or mucosal infections (herpes, measles, mumps, smallpox and rubella), hepatic infections (hepatitis A, B, C, E), blood infections (acquired immunodeficiency syndrome) and hemorrhagic fever (yellow fever, Ebola hemorrhagic fever). Viruses are the most abundant and diverse biological entities on Earth and this is the reason for the high incidence of viral infections. In addition, some viruses are etiological agents in the development of human tumors, particularly cervical cancer and hepatic cancer.

The main method and most cost-effective strategy for preventing viral infections is through vaccination, which is meant to prevent outbreaks by increasing immunity. Vaccines for the prevention of several common acute viral infections, such as polio, rubella, measles, mumps, Influenza, yellow fever, encephalitis, rabies, smallpox and hepatitis B were developed during the 20th century and are available on a large scale. Efforts to develop safe and effective vaccines against viruses that cause chronic infections, such as human immunodeficiency virus or hepatitis C virus did not give the expected results.

For many viral infections, only symptomatic treatment is indicated, while it is expected the immune system to fight off the virus. However, there are high-virulence viruses that cause serious viral infections where antiviral treatment is essential for patient survival. Although great efforts have been made to find effective medication, there are still no drugs that truly cure viral infections. Moreover, due to the ability of viruses to undergo rapid mutations, the mechanisms involved in developing resistance to antiviral drugs are activated in most cases. As resistance toward antiviral drugs is becoming a global health threat, there is an intrinsic need to identify new scaffolds that are useful in discovering innovative, less toxic and highly active antiviral agents.

Both viruses and bacteria may colonize the nasopharynx (NP) and oropharynx (OP) without causing infection. Advances in molecular testing and microbial antigen detection with enhanced sensitivity may allow detection of colonization or postinfectious shedding of respiratory pathogens without clinical significance. Respiratory viruses, such as the herpes viruses, including Epstein-Barr (EBV), herpes simplex virus (HSV), and cytomegalovirus (CMV), are associated with chronic intermittent asymptomatic nucleic acid shedding.

Streptococcal carriers are at low risk to spread GABHS to close contacts. They do not require antibiotic treatment and are at minimal risk for development of rheumatic fever. Streptococcal carriage may persist for many months and frequently poses diagnostic challenges when a symptomatic viral URI develops in carriers. The low predictive value of throat swabs relates to the prevalence of carrier rates, and neither the blood agar plate culture nor the rapid antigen tests can accurately differentiate individuals with true GABHS pharyngitis from GABHS carriers. Studies have shown that only 40%–50% of the children with GABHS isolated from the upper respiratory tract who presented with symptoms of tonsillitis or pharyngitis demonstrated a systemic immune response [16–18].

When Group A strep is cultured from the OP and associated with an antibody response characteristic of a true infection, CRP will elevate 80%–90% of the time [15, 17]. Conversely, patients with a negative initial CRP test seldom show a rise in antibody titer, and 96% have CRP <10 mg/mL. The high carrier rate of GABHS and false-positive diagnoses may contribute to the apparent “failure” rate of approximately 20% with penicillin therapy. Valkenburg et al. have shown that an antistreptococcal antibody titer is more accurate than a throat culture in predicting therapeutic outcome.

Differentiation of infection from colonization requires the demonstration of an antibody response. However, proving this immune response is time-consuming and may lead to false-negative results following appropriate antibiotic therapy. A study by Ivaska et al. showed that in 83 patients presenting with pharyngitis, there was no significant difference in the mean initial serum antistreptolysin O (ASO) levels between the GABHS and non-GABHS patients and only 5 patients showed a 2-fold ASO increase in paired serum samples. Of the 5 patients with an antibody response, 3 of them were GABHS positive, 1 of them was GCBHS positive, and 1 was negative for streptococci by throat culture. Conversely, blood MxA levels were found to be elevated in 79% of patients with viral pharyngitis and remained low in 90% of patients with GABHS without virus detection.

Viral infections are a common cause of morbidity in patients with PIDDs. They can be a clue to the diagnosis when persistent or unusually severe and can represent a significant management challenge.

Testing for defects related to herpes simplex encephalitis often involves genetic sequencing although functional analyses are available on a research basis. Table 3 lists the currently recognized genetic causes of susceptibility to herpes simplex encephalitis.

The diagnosis of enteroviral meningoencephalitis in PIDD patients requires a specific description. In a patient with agammaglobulinemia detection of enterovirus is surprisingly difficult. PCR analysis of cerebrospinal fluid or stool (less specific) should be performed. However, it is not unusual for children with agammaglobulinemia and suggestive clinical features to require a brain biopsy for diagnosis. The biopsy tissue can be tested for enterovirus by PCR. In a patient who presents with CNS enteroviral disease, identification of an immune deficiency is critical because of the prognostic implications. The strong association of CNS enteroviral disease with agammaglobulinemia supports a strategy that begins with enumeration of peripheral blood B cells by flow cytometry. Only if that is negative and there are no other secondary immune deficiencies should alternatives such as CD40L or CVID be sought. A reasonable secondary screen would be to measure immunoglobulin levels and responses to vaccines.

The aim of the present study was to prepare anti-BV mAbs, which is for the diagnosis of BV infection, and provide a foundation for the development of rapid and specific methods.

Fetuses and neonates are susceptible to a wide variety of viral infections most commonly involving the central nervous system (CNS) in greater frequency than adults (81). Infections of the CNS are a very common worldwide health problem in childhood with significant morbidity and mortality. In children, viruses are the most common cause of CNS infections, followed by bacteria, and less frequently by fungi and other causes. Advances in the prenatal and perinatal care together with technological advent of imaging modalities have enabled timely detection and detailed exploration of symptoms and signs in the neonatal population starting from the fetal life. Although imaging is practically unable to set the diagnosis of viral infection in the fetuses and neonates, moreover to reveal the pathogens, it has, however, the potential to accurately suggest this scenario, map the extent of involvement and direct the investigation and the consultation accordingly. Additionally, it may reveal complications from viral infections that may cause confusion and usually require special treatment (81).

Some imaging findings are highly suggestive of CNS viral infections in fetuses and neonates (82). Familiarity with the clinical course, the route of transmission and the imaging appearances usually proves helpful in reaching the correct diagnosis and in prompting timely treatment. In general, sequelae of an intrauterine infection reflect a combination of the pathogens and the stage of fetal development at which the exposure occurred (83). Congenital infections, occurring during the second and third trimester, may persist in the neonate affecting its general and neurologic status (83). However, as a rule of thumb, the later the diagnosis of congenital infections is made, the more difficult it is to identify the agent. Additionally, the imaging findings may become non-specific and less conspicuous as incomplete white matter myelination may interfere (83).

If maternal viral infection is suspected, combining prenatal ultrasound and fetal magnetic resonance imaging (MRI) may document the extent of tissue damage and therefore contribute to treatment and counselling (84). Neonatal head ultrasound, sometimes computed tomography (CT), but mainly MRI (Figs. 1 and 2) may reveal sequelae from congenital viral infections (i.e., microcephaly, dystrophic periventricular calcifications, brain atrophy), which may even suggest the causative virus, such as cytomegalovirus (CMV) (85). In previously healthy neonates with viral infection, the imaging investigation of CNS begins with head ultrasound and if further imaging investigation is required, MRI is the modality of choice, even in an emergency setting (86). Non-complicated meningitis is easier to be recognised clinically; however, since complications of meningitis, such as abscesses, infarcts, venous thrombosis, or extra-axial empyemas are difficult to diagnose clinically, imaging plays a crucial role (87).

The virome is the community of viruses found in a particular ecosystem. Viromes characterized from animals and human are comprised of both prokaryotic and eukaryotic viruses. Commensal bacteriophages, which make up the major fraction of the fecal virome, can modulate the microbial community in the host body and influence host immunity. Although typically a smaller fraction of the enteric virome, mammalian viruses may cause diseases such as diarrhea resulting in malnutrition and dehydration. Deep sequencing of wild animal fecal viromes also unveiled many eukaryotic viruses whose pathogenicity, if any, remain mostly unknown. In the past, emergences of human infectious diseases have been initiated by zoonotic viruses originating from bats, rodents, and non-human primates. Ebola virus likely from bats, human immunodeficiency virus (HIV) from chimpanzees, and the Middle East respiratory syndrome coronavirus (MERS-CoV) from camels, have caused very large economic and public health disruptions. Therefore, it is important to identify the viruses within animals with the potential to spill over into human and result in pathogenic infections. Such zoonoses may take different routes including fecal-oral transmission. Outbreaks of zoonotic enteric viruses belonging to the families of Picornaviridae, Adenoviridae, Caliciviridae, and Reoviridae cause important enteric diseases in humans. Moreover, alteration of enteric virome in humans also affect bacterial microbiome stability and influence diseases such as inflammatory bowel disease and ulcerative colitis. Studies of intestinal and fecal bacterial communities have received much attention relative to that of the gut virome.

Cynomolgus macaque, a non-human primate species widely distributing across Southeast Asian countries have long been used for biological research including on influenza virus, Ebola virus, and simian/human immunodeficiency virus (SIV/HIV). The National Primate Research Center of Thailand–Chulalongkorn University (NPRCT-CU), maintains a colony of cynomolgus macaques captured from disturbed natural habitats. Although well-established biosecurity protocols are used to screen infectious viruses such as herpes B virus, simian retrovirus (SRV), simian immunodeficiency virus (SIV), simian-T-lymphotropic viruses (STLV) and foamy virus that might cause a sporadic outbreaks, the transmission of other viruses from wild-originating macaques remains possible. In addition, captivity may also influence gut microbiome and virome. A recent study illustrated that replacing the gut microbiome of inbred laboratory mice with that of wild mice restored their immune responses to better mimic those of wild animals. Here, we characterized and compared the fecal virome of wild and captive macaques and identified novel macaque viruses.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the central nervous system, which typically follows acute viral or bacterial infection or vaccination. ADEM is characterized by widespread demyelination that predominantly involves the white matter of the brain and spinal cord. Numerous infectious agents, mostly nonspecific upper respiratory tract infections, have been linked to ADEM. Hepatitis virus is a rare cause of ADEM. One case of hepatitis C virus (HCV) and two cases of hepatitis A virus with ADEM have been reported.1-3

We report a case of ADEM associated with HCV infection. This is the first case of ADEM with anti-HCV antibody in the cerebrospinal fluid (CSF).

Up to 90% of the global population is infected with the α-herpesvirus Herpes simplex virus type I (HSV-1). Whilst HSV-1 is largely responsible for outbreaks of vesicular oral skin lesions (fever blisters, or cold sores), it can also cause a variety of more severe diseases including encephalitis, meningitis and keratitis,. Furthermore, the frequency of association with genital lesions (previously associated mainly with HSV-2 infection) is increasing. As co-infection with HSV is a significant contributing factor to transmission of the Human Immunodeficiency Virus (HIV), our understanding of HSV disease, and herpesviruses in general, has wide implications for global healthcare.

Like all herpesviruses, HSV-1 establishes lytic (epithelial cells) and asymptomatic latent infection (sensory neurons in trigeminal and sacral ganglia) which undergoes periodic reactivation. The equilibrium between these two infection states requires a fine balance between innate and adaptive immune responses, and viral immune evasion mechanisms. Whilst aspects of the HSV-1 replication cycle have been intensively investigated, there remain gaps in our understanding of the complexity of virus:host interactions. For example, a proteomics study identified over 100 changes in the cellular proteome within the first 6h of infection with HSV-1, and a recent analysis of virion-incorporated cellular proteins found that about 30% of these directly affected virus growth.

To systematically identify host factors (HFs) required for viral replication, RNAi screens have been performed with a range of different RNA and DNA viruses including HIV-1,,, Influenza A virus,,, Hepatitis C virus, West Nile virus, Dengue virus, Enterovirus and Vaccinia virus,. The overlap between the results of these studies is generally very low, reflecting either differences in biology, or different experimental set-ups, cutoff and selection criteria. In addition, microenvironmental effects might also play a role for the differences of the results.

Whilst loss-of-function siRNA screens provide functional information on specific genes, protein interaction studies can provide insight into the mechanism of action by identifying physical interaction partners between pathogen and host. Genome-scale virus-host protein interaction screens using the yeast-two-hybrid system have been performed for HCV, Influenza A virus, Epstein Barr virus (EBV), Vaccinia virus,, SARS coronavirus and several non-human viruses. Based on these genome-scale studies and individual interactions found by literature curation, several virus-host interaction databases have been created including the HIV-1, human protein interaction database at NCBI, VirHostNet, VirusMINT, PIG and HPIDB. Although there is little overlap between individual cellular interactors of different viruses, targeting of a number of cellular processes such as cell cycle regulation, nuclear transport and immune response appears to be conserved.

Understanding the complex interplay between viral and host components is critical to the definition of herpesvirus infection and pathogenesis. As herpesviruses encode a large number of proteins, in contrast to small RNA viruses such as HIV and Influenza, many cellular processes may be directly affected by viral proteins, and whilst there exists a wealth of information on individual viral proteins, there remain large gaps in our understanding of the HSV-1 life cycle and its interaction with its host. Here, we present data from the first integrative and systematic screening approach to characterise the role of cellular proteins in the HSV-1 life cycle. A genome-scale RNAi knockdown screen to identify HFs functionally influencing HSV-1 replication was performed in parallel with a yeast two-hybrid (Y2H) protein interaction screen to simultaneously gain insight into potential mechanisms of action. Combined analyses confirmed the importance of known cellular proteins involved in processes such as cell cycle, proteins transport and gene expression important for virus replication. Furthermore, we identified a subunit of the Mediator multi-protein complex, Med23, as a key regulator of IFN-λ induction, which appears to be of crucial significance for the control of HSV-1 both in vitro and in vivo. These data demonstrate the power of a combined screening strategy to investigate pathogen:host interactions and identify novel host factors and cellular pathway targets for the development of essential clinical interventions.

The true incidence of viral sepsis, particularly in the pediatric population, remains unknown. Since bacterial sepsis is amenable to treatment and is presumably more common, viral testing is frequently foregone in the acute presentation of sepsis. However, a recent study of adult patients with sepsis showed that viral respiratory pathogens, namely influenza A virus, human metapneumovirus, coronavirus, and respiratory syncytial virus (RSV), were overlooked in 70% of patients (7). In a multi-national epidemiological study of children with severe sepsis, an infectious etiology was only proven in 65% of patients and out of these, approximately one-third had a viral infection (8). The most frequent sites of infection were the respiratory tract (40%) and bloodstream (20%), with rhinovirus, RSV, and adenovirus most commonly isolated. In contrast, the Australia and New Zealand sepsis study group identified a pathogen in approximately 50% of patients with sepsis and septic shock (9). Of these patients, only one-fifth had a viral etiology, with RSV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella zoster virus (VZV) and influenza being the most common viruses identified in this study. Recently, Ames et al. reported that 16% of pediatric patients who presented with septic shock had a primary viral disease (10). In another study of neonates with sepsis, bacterial etiology was found in only approximately 15% of cases, making viral infection more likely as a plausible cause of sepsis in these patients (11).

In the pediatric intensive care unit (PICU), influenza virus is a leading cause of viral sepsis and caries an especially high mortality rate (12). RSV has also been found to cause severe bronchiolitis and may present with sepsis, especially in children with history of premature birth, chronic lung disease, congenital heart disease or primary immunodeficiency (13, 14). Sepsis has also been observed in neonates with HSV, human parechovirus (HPeV) and enteroviral infection (15–18). Patients with immunodeficiency due to human immunodeficiency virus (HIV) infection are highly susceptible to viral sepsis depending on the stage of disease and access and response to the treatment (19). In these patients, common viral infections observed to cause sepsis include RSV, influenza, parainfluenza, adenovirus, CMV, EBV, and VZV (19). Diarrheal diseases secondary to viral infections can also lead to sepsis, especially in developing countries (20). Although rare, rotavirus has been associated with sepsis due to bacterial coinfection (21). Despite several large studies on viral sepsis in general (ref as above), as well as on specific viruses, in the absence of routine viral testing during the diagnostic evaluation of sepsis, the true incidence of viral infection as the cause of sepsis remains unclear.

For patients with a suspected central nervous system (CNS) infection, rapid and accurate diagnosis is vital to determine treatment and improve prognosis. The differential diagnosis of such patients includes infectious etiologies, of which viruses are the most common, but also non-infectious etiologies, such as auto-immune diseases. Nonetheless, in more than half of cases, the cause remains unknown. Identification of a virus can aid in patient management as it may initiate specific antiviral treatment, or cease or prevent ineffective antiviral, antibiotic, and/or immunosuppressive treatments, which all have potential harmful side effects. For example, when differentiating between an auto-immune and viral origin, immune suppression could lead to deleterious outcomes when caused by an unidentified virus.

During the last two decades, conventional diagnostics for viral CNS infections have shifted from non-specific culturing techniques towards highly-specific viral nucleic acid amplification tests, like quantitative polymerase chain reaction (qPCR), or the detection of host-mediated antibody production to the virus (e.g., ELISA). Although these latter assays have greatly increased diagnostic sensitivity, a limitation is that they only target an individual virus or a subset of related viruses. The number of viruses that have been associated with CNS infections currently comprises more than 100, with several more discovered in the last decade. Consequently, a comprehensive diagnostic panel would include many specific tests. Since this is unachievable for routine diagnostics, only a small selection of viruses commonly associated with CNS infections are included in most diagnostic panels (e.g., herpes simplex virus 1/2, enteroviruses, and parechoviruses). Other pathogens are usually not examined, or are tested for at a later stage of the disease, by which time irreversible pathology could have occurred.

Metagenomics is a recent and promising development in microbiology, which is theoretically able to detect all viruses, including known, unexpected, and novel species. The sensitivity of such assays is generally determined by three factors: (1) The concentration of viruses in a clinical sample, (2) the amount of background (competing) RNA and DNA, and (3) the sequencing depth. Generally, metagenomics assays are poor or unable to detect viruses in a clinical specimen because of the low viral load relative to the high concentration of background RNA and DNA. To overcome this, viral metagenomic assays enrich the viral content of a sample. Virus discovery cDNA-AFLP (amplified fragment length polymorphism) next-generation sequencing (VIDISCA-NGS) is one of the available assays for viral metagenomics. Characteristic for VIDISCA-NGS is the fragmentation of ds(c)DNA, which is done using a frequent-cutting restriction enzyme, and thus different from the random shearing, random PCR amplification, or transposon-based shearing techniques used in most viral metagenomic assays. The method was first described with the discovery of human coronavirus NL63, and since has discovered and detected a wide range of viruses in various sample types. VIDISCA-NGS could be an ideal tool for the broad range detection of viruses in cerebrospinal fluid (CSF).

CSF is a distinct bodily fluid containing a relatively low number of host cells. Even with mild pleiocytosis, as seen during most viral CNS infections, CSF has a far lower cellular content than a similar volume of blood, respiratory, or fecal material. This low amount of background could influence NGS results in two ways: (1) It may decrease the nucleic acid extraction yield if the total nucleic acid content is too low, or (2) it may be beneficial, as proportionally less sequence space is taken by competing background RNA or DNA. Considering the potential benefit viral metagenomics may have for future viral diagnostics in encephalitis, we determined the capability of VIDISCA-NGS to detect viruses in CSF samples from patients with suspected CNS infections.

Herpes simplex viruses are ubiquitous and cause life-long infections of their human hosts. HSV infections are primarily acquired at mucosal surfaces where initial epithelial cell infections can lead to disease manifestations that include herpes labialis, genital herpes, gingivostomatitis, herpetic whitlow, encephalitis, aseptic meningitis, neonatal herpes, and stromal keratitis. HSV-1 and HSV-2 share common structural features, including a large double-stranded DNA genome protected by a nucleocapsid, a tegument layer containing viral proteins that are delivered to the host cell early in infection, and an envelope derived from host membranes studded with viral glycoproteins that facilitate attachment and entry into host cells. While HSV-1 and HSV-2 are similar, they share only ~55% nucleotide identity.

Lytic HSV infection of a cell begins with initial attachment to negatively charged cell surface heparan sulfate and chondroitin sulfate glycosaminoglycans, followed by stable attachment of viral glycoproteins to cell surface receptors and fusion of the viral envelope to the plasma membrane or internal membranes. Fusion of viral and host membranes enables delivery of the viral nucleocapsid and tegument proteins to the cytoplasm. After the HSV nucleocapsid arrives at the nucleus and delivers the viral genome, HSV genes are expressed in an ordered temporal cascade. Viral egress requires primary envelopment of the genome-containing capsid at the inner nuclear membrane, fusion with the outer nuclear membrane and final envelopment at the trans-Golgi network. Mature virions then exit through the cellular secretory system.

All stages of the HSV replication cycle offer potential targets for direct-acting antiviral (DAA) therapy. However, DAAs can be undermined by the emergence of drug resistant mutant viruses. Anti-HSV DAAs acyclovir and foscarnet offer examples of the hazards of drug resistance. These drugs interrupt HSV genome replication by different mechanisms of action. Acyclovir is a nucleoside analogue prodrug that selectively targets HSV infected cells through the action of the HSV thymidine kinase (TK) enzyme, which efficiently phosphorylates acyclovir and facilitates incorporation into nascent viral DNA genomes by the HSV DNA polymerase enzyme; incorporation of acyclovir into viral DNA terminates genome replication. By contrast, the pyrophosphate analogue foscarnet blocks viral genome replication by directly inhibiting HSV DNA polymerase activity. Though resistance to acyclovir occurs at a low prevalence (≤1%) in immunocompetent patients, immunocompromised patients experience much higher rates (4–10%). Unsurprisingly, resistance to acyclovir, and its derivatives, and to foscarnet, has been mapped to mutations in the viral thymidine kinase and the DNA polymerase catalytic subunit, respectively. Currently, Abreva (n-docosanol) is the only over-the-counter topical antiviral for herpes labialis. Abreva is incorporated into the cellular plasma membrane and prevents fusion steps essential for HSV-1 entry into epithelial cells. However, it must be applied repeatedly throughout the day due to rapid plasma membrane turnover and the subsequent loss of n-docosanol. This host-targeted antiviral mechanism prevents development of viral resistance, but Abreva is only approved for perioral lesions, so there is a still a gap in treatment for lesions in other areas of the body.

Like Abreva, there is potential for more broadly-acting antiviral drugs that exploit the physical structure of the HSV virion and block early stages of infection, such as attachment and penetration. In this study, we explored the potential of the plant-derived photosensitizing agent OrthoquinTM to mediate photodynamic inactivation (PDI) of virions. The clinical utility of Orthoquin PDI of oral biofilms is an area of active investigation and there is clear potential for wider range of clinical applications. The basis of PDI is the photodynamic effect, which has been exploited in photodynamic therapy (PDT) for treatment of cancers and age-related macular degeneration. In PDT, photosensitizer compounds when exposed to visible light react with oxygen to generate reactive oxygen species (ROS) that include singlet oxygen. ROS damage proteins, nucleic acids and lipids, which can lead to cell death. Some of the most well-known photosensitizing molecules for PDT are based on a tetrapyrrolic core and are found in naturally occurring pigments, such as heme, chlorophyll, and bacteriochlorophyll. The accepted phototoxic mechanism for these types of photosensitizers involves the formation of an excited triplet state upon light absorption that can participate in electron (Type 1) or energy (Type 2) transfer processes. Type 1 electron transfer reactions typically lead to the formation of radical species like superoxide or hydroxyl radicals, whereas Type 2 energy transfer produces cytotoxic singlet oxygen. It is possible for a photosensitizer to initiate both Type 1 and 2 photoprocesses simultaneously, depending on the specific chemistry of the photosensitizing agent and its environment. Due to the high reactivities and short lifetimes of oxidizing molecules, it is expected that only viral structures in close proximity to activated photosensitizing compounds will be affected.

Orthoquin has been shown to have bacteriocidal properties and to disrupt bacterial biofilms without causing overt inflammation. In this study we investigated Orthoquin’s anti-herpesviral properties and mechanism of action. We showed that sub-cytotoxic doses of Orthoquin reduced HSV-1 and HSV-2 plaque formation in a light-dependent manner, whereas high doses displayed light-independent antiviral effects. Surprisingly, HSV-2 displayed high intrinsic photosensitivity, so we focused primarily on the relatively photo-resistant HSV-1. PDI of HSV-1 required close proximity between Orthoquin and the viral inoculum, whereas pre-treatment of target host cells with Orthoquin exposed to light had no effect. High doses of Orthoquin disrupted immunodetection of a subset of HSV-1 structural proteins by a pan-anti-HSV-1 polyclonal antibody, suggesting that PDI may cause physical damage to proteins on the virion exterior that prevents infection. Finally, we demonstrated light-dependent Orthoquin PDI of adenovirus infection and light-independent inhibition of vesicular stomatitis virus (VSV) infection.