Showing papers in "Reviews in Medical Virology in 2019"

Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta‐analysis

Abstract: Cytomegalovirus (CMV) infection does not usually produce symptoms when it causes primary infection, reinfection, or reactivation because these three types of infection are all controlled by the normal immune system. However, CMV becomes an important pathogen in individuals whose immune system is immature or compromised, such as the unborn child. Several vaccines against CMV are currently in clinical trials that aim to induce immunity in seronegative individuals and/or to boost the immunity of those with prior natural infection (seropositives). To facilitate estimation of the burden of disease and the need for vaccines that induce de novo immune responses or that boost pre-existing immunity to CMV, we conducted a systematic survey of the published literature to describe the global seroprevalence of CMV IgG antibodies. We estimated a global CMV seroprevalence of 83% (95%UI: 78-88) in the general population, 86% (95%UI: 83-89) in women of childbearing age, and 86% (95%UI: 82-89) in donors of blood or organs. For each of these three groups, the highest seroprevalence was seen in the World Health Organisation (WHO) Eastern Mediterranean region 90% (95%UI: 85-94) and the lowest in WHO European region 66% (95%UI: 56-74). These estimates of the worldwide CMV distribution will help develop national and regional burden of disease models and inform future vaccine development efforts.

The interplay between vitamin D and viral infections.

Abstract: The pleiotropic role of vitamin D has been explored over the past decades and there is compelling evidence for an epidemiological association between poor vitamin D status and a variety of diseases. While the potential anti-viral effect of vitamin D has recently been described, the underlying mechanisms by which vitamin D deficiency could contribute to viral disease development remain poorly understood. The possible interactions between viral infections and vitamin D appear to be more complex than previously thought. Recent findings indicate a complex interplay between viral infections and vitamin D, including the induction of anti-viral state, functional immunoregulatory features, interaction with cellular and viral factors, induction of autophagy and apoptosis, and genetic and epigenetic alterations. While crosstalk between vitamin D and intracellular signalling pathways may provide an essential modulatory effect on viral gene transcription, the immunomodulatory effect of vitamin D on viral infections appears to be transient. The interplay between viral infections and vitamin D remains an intriguing concept, and the global imprint that vitamin D can have on the immune signature in the context of viral infections is an area of growing interest.

Emerging trends of Nipah virus: A review.

Abstract: Since emergence of the Nipah virus (NiV) in 1998 from Malaysia, the NiV virus has reappeared on different occasions causing severe infections in human population associated with high rate of mortality. NiV has been placed along with Hendra virus in genus Henipavirus of family Paramyxoviridae. Fruit bats (Genus Pteropus) are known to be natural host and reservoir of NiV. During the outbreaks from Malaysia and Singapore, the roles of pigs as intermediate host were confirmed. The infection transmitted from bats to pigs and subsequently from pigs to humans. Severe encephalitis was reported in NiV infection often associated with neurological disorders. First NiV outbreak in India occurred in Siliguri district of West Bengal in 2001, where direct transmission of the NiV virus from bats-to-human and human-to-human was reported in contrast to the role of pigs in the Malaysian NiV outbreak. Regular NiV outbreaks have been reported from Bangladesh since 2001 to 2015. The latest outbreak of NiV has been recorded in May, 2018 from Kerala, India which resulted in the death of 17 individuals. Due to lack of vaccines and effective antivirals, Nipah encephalitis poses a great threat to public health. Routine surveillance studies in the infected areas can be useful in detecting early signs of infection and help in containment of these outbreaks.

Progressive multifocal leukoencephalopathy and anti-CD20 monoclonal antibodies: What do we know after 20 years of rituximab.

Abstract: In 1997, rituximab was the first monoclonal antibody clinically approved for the treatment of cancer. Ten years later, progressive multifocal leukoencephalopathy (PML), until that time a rare opportunistic infection mostly seen in AIDS patients, was added as a black box warning after retrospective case-control studies showed an increased incidence in both B-cell lymphoproliferative disorders and autoimmune diseases. Despite more than 5 million worldwide exposures to date (and about 500 000 new exposures per year), insufficient data collection has hampered identification of risk minimization strategies, and concerns have been raised about a class effect extending to the newer anti-CD20 monoclonal antibodies (ofatumumab, obinutuzumab, and ocrelizumab). Here, we report current PML case counts registered in the FAERS and EudraVigilance databases and comment on severe CD4+ T lymphopenia as a plausible common mechanism of action for anti-CD20 antibodies in causation of PML.

Influenza vaccine: Where are we and where do we go?

Abstract: The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross-reactive immune response. The lack of viral genome in VLP and M2e-based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome-based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.

The dawn of phage therapy.

Abstract: Bacteriophages or phages, being the most abundant entities on earth, represent a potential solution to a diverse range of problems. Phages are successful antibacterial agents whose use in therapeutics was hindered by the discovery of antibiotics. Eventually, because of the development and spread of antibiotic resistance among most bacterial species, interest in phage as therapeutic entities has returned, because their noninfectious nature to humans should make them safe for human nanomedicine. This review highlights the most recent advances and progress in phage therapy and bacterial hosts against which phage research is currently being conducted with respect to food, human, and marine pathogens. Bacterial immunity against phages and tactics of phage revenge to defeat bacterial defense systems are also summarized. We have also discussed approved phage-based products (whole phage-based products and phage proteins) and shed light on their influence on the eukaryotic host with respect to host safety and induction of immune response against phage preparations. Moreover, creation of phages with desirable qualities and their uses in cancer treatment, vaccine production, and other therapies are also reviewed to bring together evidence from the scientific literature about the potentials and possible utility of phage and phage encoded proteins in the field of therapeutics and industrial biotechnology.

Subacute sclerosing panencephalitis.

Abstract: Subacute sclerosing panencephalitis (SSPE) is a slowly progressive brain disorder caused by mutant measles virus. SSPE affects younger age groups. SSPE incidence is proportional to that of measles. High-income countries have seen substantial decline in SSPE incidence following universal vaccination against measles. SSPE virus differs from wild measles virus. Measles virus genome recovered from the autopsied brain tissues demonstrates clustered mutations in virus genome particularly in the M gene. These mutations destroy the structure and functioning of the encoded proteins. Complete infectious virus particle has rarely been recovered from the brain. Human neurons lack required receptor for entry of measles virus inside the neurons. Recent in vitro studies suggest that mutations in F protein confer hyperfusogenic properties to measles virus facilitating transneuronal viral spread. The inflammatory response in the brain leads to extensive tissue damage. Clinically, SSPE is characterized by florid panencephalitis. Clinically, SSPE is characterized by cognitive decline, periodic myoclonus, gait abnormalities, vision loss, and ultimately to a vegetative state. Chorioretinitis is a common ocular abnormality. Electroencephalography (EEG) shows characteristic periodic discharges. Neuroimaging demonstrates periventricular white matter signal abnormalities. In advanced stages, there is marked cerebral atrophy. Definitive diagnosis requires demonstration of elevated measles antibody titers in cerebrospinal fluid (CSF). Many drugs have been used to stabilize the course of the disease but without evidence from randomized clinical trials. Six percent of patients may experience prolonged spontaneous remission. Fusion inhibitor peptide may, in the future, be exploited to treat SSPE. A universal vaccination against measles is the only proven way to tackle this menace currently.

Inactivation methods for whole influenza vaccine production.

Abstract: Despite tremendous efforts toward vaccination, influenza remains an ongoing global threat. The induction of strain-specific neutralizing antibody responses is a common phenomenon during vaccination with the current inactivated influenza vaccines, so the protective effect of these vaccines is mostly strain-specific. There is an essential need for the development of next-generation vaccines, with a broad range of immunogenicity against antigenically drifted or shifted influenza viruses. Here, we evaluate the potential of whole inactivated vaccines, based on chemical and physical methods, as well as new approaches to generate cross-protective immune responses. We also consider the mechanisms by which some of these vaccines may induce CD8+ T-cells cross-reactivity with different strains of influenza. In this review, we have focused on conventional and novel methods for production of whole inactivated influenza vaccine. As well as chemical modification, using formaldehyde or β-propiolactone and physical manipulation by ultraviolet radiation or gamma-irradiation, novel approaches, including visible ultrashort pulsed laser, and low-energy electron irradiation are discussed. These two latter methods are considered to be attractive approaches to design more sophisticated vaccines, due to their ability to maintain most of the viral antigenic properties during inactivation and potential to produce cross-protective immunity. However, further studies are needed to validate them before they can replace traditional methods for vaccine manufacturing.

The discovery and global distribution of novel mosquito-associated viruses in the last decade (2007-2017).

Abstract: In the last decade, virus hunting and discovery has gained pace. This achievement has been driven by three major factors: (a) advancements in sequencing technologies, (b) scaled-up routine arbovirus surveillance strategies, and (c) the "hunt" for emerging pathogens and novel viruses. Many novel viruses have been discovered from a myriad of hosts, vectors, and environmental samples. To help promote understanding of the global diversity and distribution of mosquito-associated viruses and facilitate future studies, we review mosquito-associated viruses discovered between years 2007 and 2017, across the world. In the analyzed period, novel mosquito-associated viruses belonging to 25 families and a general group of unclassified viruses were categorized. The top three discovered novel mosquito-associated viruses belonged to families Flaviviridae (n=32), Rhabdoviridae (n=16), and Peribunyaviridae (n=14). Also, 67 unclassified viruses were reported. Majority of these novel viruses were identified from Culex spp, Anopheles spp, Aedes spp, and Mansonia spp mosquitoes, respectively. Notably, the number of these discovered novels is not representative of intercontinental virus diversity but rather is influenced by the number of studies done in the study period. Some of these newly discovered mosquito-associated viruses have medical significance, either directly or indirectly. For instance, in the study period, 14 novel mosquito-borne viruses that infect mammalian cells in vitro were reported. These viruses pose a danger to the global health security on emerging viral diseases. On the other hand, some of the newly discovered insect specific viruses described herein have potential application as future biocontrol and vaccine agents against known pathogenic arboviruses. Overall, this review outlines the crucial role played by mosquitoes as viral vectors in the global virosphere.

Virus detection by transmission electron microscopy: Still useful for diagnosis and a plus for biosafety

Abstract: Transmission electron microscopy (TEM) is the only imaging technique allowing the direct visualization of viruses, due to its nanometer-scale resolution. Between the 1960s and 1990s, TEM contributed to the discovery of many types of viruses and served as a diagnostic tool for identifying viruses directly in biological samples, either in suspension or in sections of tissues or mammalian cells grown in vitro in contact with clinical samples. The diagnosis of viral infections improved considerably during the 1990s, with the advent of highly sensitive techniques, such as enzyme-linked immunosorbent assay (ELISA) and PCR, rendering TEM obsolete for this purpose. However, the last 20 years have demonstrated the utility of this technique in particular situations, due to its "catch-all" nature, making diagnosis possible through visualization of the virus, without the need of prior assumptions about the infectious agent sought. Thus, in several major outbreaks in which molecular techniques failed to identify the infectious agent, TEM provided the answer. TEM is also still occasionally used in routine diagnosis to characterize infections not diagnosed by molecular assays. It is also used to check the microbiological safety of biological products. Many biopharmaceuticals are produced in animal cells that might contain little-known, difficult-to-detect viruses. In this context, the "catch-all" properties of TEM make it possible to document the presence of viruses or virus-like particles in these products.

Expressional activation and functional roles of human endogenous retroviruses in cancers.

Abstract: Human endogenous retroviruses (HERVs) are widely believed to be remnants of ancestral germ line infections by exogenous retroviruses. Although HERVs are deemed as "nonfunctional DNAs" due to loss of most of their viral protein coding capacity during evolution as part of the human genome, cumulative evidences are showing the expressional activation and potential roles of HERVs in diseases especially cancers. Work by other researchers and us has observed the dysregulation of HERVs in cancers, identified new HERV-related genes, and revealed their potential importance in cancer development. Here, we summarized the current knowledge on the mechanisms of the expressional activation and functional roles of HERVs, with a focus on the H family HERV (HERV-H), in carcinogenesis. HERV expression is regulated by external chemical or physical substances and exogenous virus infection, as well as host factors such as epigenetic DNA methylation, transcription factors, cytokines, and small RNAs. Diverse roles of HERVs have been proposed by acting in the forms of noncoding RNAs, proteins, and transcriptional regulators during carcinogenesis. However, much remains to be learnt about the contributions of HERVs to human cancers. More investigation is warranted to elucidate the functions of these "fossil remnants" yet important viral DNAs in the human genome.

Serum lipid profile as a predictor of dengue severity: A systematic review and meta-analysis

Abstract: Dengue virus is known to modulate host cell lipid metabolism in order to promote efficient viral replication. Recent studies have focused on circulating lipids as potential biomarkers of dengue severity; however, the results obtained so far lack the consistency to establish a definite relationship between the two. Therefore, in the present study, we investigated serum lipids as potential biomarkers of dengue severity by conducting a meta-analysis of the currently available clinical data. Nine studies that evaluated 1,953 patients were included in the review, many of which were cross-sectional (44.4%) and conducted in Asian countries (55.5%). These studies observed the presence of lipids in serum samples (77%) of patients in the acute phase of the disease (88.8%). Circulating total-cholesterol (P = .001) and LDL (P = .001) levels, but not HDL (P = .07), VLDL (P = .9) and triglyceride (P = .57) levels, were inversely and significantly correlated with dengue severity. Total cholesterol (P ≤ .001) and LDL (P = .001) were also useful in determining the risk of hypovolemic shock in patients with severe dengue. Subgroup analysis showed that factors, such as design (cross-sectional vs cohort), racial-ethnic differences (Asian vs Latin Americans), and age range (children vs adult) influenced the correlation and also contributed to the high level of heterogeneity in the studies. Our meta-analysis demonstrates that total-cholesterol and LDL-cholesterol levels should be explored as routine laboratory markers for dengue severity, as they will help in employing an appropriate patient therapy, and thus optimize the use of available resources.

The interplay between viruses and TRIM family proteins

Abstract: Novel therapeutic options are urgently needed to improve the global treatment of viral infections. Tripartite motif (TRIM) family proteins are involved in various biological and cellular functions including differentiation, development, proliferation, oncogenesis, innate immunity, and viral autophagy. Various TRIM proteins show antiviral properties against different viral infections and are now transitioning from ubiquitin proteins to an efficient and emerging therapeutic class of proteins. TRIM proteins combat viruses by targeting them at pre/post transcription levels. This review summarizes the comprehensive roles of different TRIM proteins along with their expression systems and their applications towards antiviral therapeutics.

Dengue viruses circulating in Indonesia: A systematic review and phylogenetic analysis of data from five decades.

Abstract: Although epidemiological and molecular epidemiological (serotype, genotype, and lineage information) data are available for several major cities in Indonesia, there is yet to be a comprehensive national study of dengue in Indonesia over time. This study was conducted to provide a comprehensive epidemiology of circulating dengue viruses (DENV) in Indonesia between 1973 and 2016. This was conducted through a systematic review of the literature and phylogenetic analysis of available DENV sequences. Available data from National Disease Surveillance System have indicated an increasing trend of dengue incidence in Indonesia over the past 50 years. Incidence rates appear to be cyclic, peaking approximately every 6 to 8 years. In contrast, the case fatality rate has decreased approximately by half with each decade since 1980. Over this 50-year time span, serotype shifts, genotype displacement within DENV-1 and DENV-2, and introduction of DENV-1 and DENV-3 genotype from other countries occurred. These events were associated with increased incidence of dengue cases. Our study also provides a valuable national snapshot of DENV genetic diversity in Indonesia that may contribute to development of more effective dengue vaccine compositions for the region.

Disease severity in respiratory syncytial virus infection: Role of host genetic variation

Abstract: Respiratory syncytial virus (RSV) infection is the most common cause of bronchiolitis and pneumonia in the pediatric population worldwide. The immunopathology of RSV infection varies considerably and severe disease occurs only in a minority of the population. There are many factors (host, viral, and environmental) that contribute to the complicated disease phenotype. In this regard, host factors are decisive for pulmonary susceptibility to RSV infection. Host genetic diversity certainly affects the balance between control of viral replication and tissue damage during RSV infection, consequently impacting on diseases outcome. In this review, we discuss the role of host genetic variation in disease caused by RSV aiming to highlight genetic risk factors for one of the most common diseases in early childhood. Our findings clearly indicate that the response of each individual to infection is influenced by genetic diversity mainly linked to the regulation of host immune responses. Future genetic association and functional studies using more powerful and consistently reproducible approaches will likely be able to confirm, refine, and expand our developing concept of RSV disease pathogenesis.

Orf virus: A promising new therapeutic agent.

Abstract: The orf virus (ORFV) is a zoonotic, epitheliotropic, DNA parapoxvirus that infects principally sheep and goats. Exposure of animals to the virus or immunization by an ORFV preparation can accentuate the severity of disease, which has provoked an interest in the underlying cellular, virological, and molecular mechanisms. The identified ORFV virulence genes and the fact that the virus can repeatedly infect a host, owing to its evasive mechanisms, contribute to the development of potent immune modulators in various animal species. ORFV has been developed as a vaccine in veterinary medicine. The unique host immune-evasion ability of ORFV has made it an important candidate for vaccine vectors and biological agents (as an oncolytic virus). Genetic modifications using ORFV to obtain safe and efficient preparations and mechanistic studies are improvements to the currently available methods for disease treatment.

BK virus: Current understanding of pathogenicity and clinical disease in transplantation

Abstract: BK polyomavirus (BKV) is an important cause of graft loss in renal transplant recipients that continues to pose a significant challenge to clinicians due to its frequently unpredictable onset, persistence, and the lack of effective antiviral agents or prevention strategies. This review covers our current understanding of epidemiology, viral transmission and disease progression, and treatment and prevention strategies that have been used to manage this disease.

Characteristics of herpes simplex virus infection and pathogenesis suggest a strategy for vaccine development.

Abstract: Herpes simplex virus (HSV) can cause oral or genital ulcerative lesions and even encephalitis in various age groups with high infection rates. More seriously, HSV may lead to a wide range of recurrent diseases throughout a lifetime. No vaccines against HSV are currently available. The accumulated clinical research data for HSV vaccines reveal that the effects of HSV interacting with the host, especially the host immune system, may be important for the development of HSV vaccines. HSV vaccine development remains a major challenge. Thus, we focus on the research data regarding the interactions of HSV and host immune cells, including dendritic cells (DCs), innate lymphoid cells (ILCs), macrophages, and natural killer (NK) cells, and the related signal transduction pathways involved in immune evasion and cytokine production. The aim is to explore possible strategies to develop new effective HSV vaccines.

Long noncoding RNAs: Novel regulators of virus-host interactions

Abstract: Long noncoding RNAs (lncRNAs) represent a key class of cellular regulators, involved in the modulation and control of multiple biological processes. Distinct classes of lncRNAs are now known to be induced by host cytokines following viral infections. Current evidence demonstrates that lncRNAs play essential roles at the host-pathogen interface regulating viral infections by either innate immune responses at various levels including activation of pathogen recognition receptors or by epigenetic, transcriptional, and posttranscriptional effects. We review the newly described mechanisms underlying the interactions between lncRNAs, cytokines, and metabolites differentially expressed following viral infections; we highlight the regulatory networks of host antiviral responses and emphasize the need for interdisciplinary research between lncRNA biology and immunology to deepen understanding of viral pathogenesis.

Viral infection in primary antibody deficiency syndromes.

Abstract: Patients with primary antibody deficiency syndromes such as X-linked agammaglobulinemia (XLA) and common variable immunodeficiency (CVID) are at increased risk of severe and invasive infection. Viral infection in these populations has been of increasing interest as evidence mounts that viruses contribute significant morbidity and mortality: this is mediated both directly and via aberrant immune responses. We explain the importance of the humoral immune system in defence against viral pathogens before highlighting several significant viral syndromes in patients with antibody deficiency. We explore historical cases of hepatitis C via contaminated immunoglobulin products, the predisposition to invasive enteroviral infections, prolonged excretion of vaccine-derived poliovirus, the morbidity of chronic norovirus infection, and recent literature revealing the importance of respiratory viral infections. We discuss evidence that herpesviruses may play a role in driving the inflammatory disease seen in a subset of patients. We explore the phenomenon of within-host evolution during chronic viral infection and the potential emergence of new pathogenic strains. We highlight novel and emerging viruses identified via deep sequencing techniques. We describe the treatment strategies that have been attempted in all these scenarios and the urgent outstanding questions for research.

An update on enterovirus 71 infection and interferon type I response.

Abstract: Enteroviruses are members of Pichornaviridae family consisting of human enterovirus group A, B, C, and D as well as nonhuman enteroviruses. Hand, foot, and mouth disease (HFMD) is a serious disease which is usually seen in the Asia-Pacific region in children. Enterovirus 71 and coxsackievirus A16 are two important viruses responsible for HFMD which are members of group A enterovirus. IFN α and β are two cytokines, which have a major activity in the innate immune system against viral infections. Most of the viruses have some weapons against these cytokines. EV71 has two main proteases called 2A and 3C, which are important for polyprotein processing and virus maturation. Several studies have indicated that they have a significant effect on different cellular pathways such as interferon production and signaling pathway. The aim of this study was to investigate the latest findings about the interaction of 2A and 3C protease of EV71 and IFN production/signaling pathway and their inhibitory effects on this pathway.

Rotavirus VP6 as a potential vaccine candidate.

Abstract: By the age of 5 years, virtually all children have been infected by group A rotavirus (RVA), which is responsible for around half million mortality annually prior to vaccination. Relatively high rate of the morbidity and mortality highlights the necessity of applying preventive procedures particularly in developing countries. Two live attenuated RVA vaccines (Rotarix and RotaTeq) are licensed and now being used in many countries worldwide. Although these vaccines are shown to reduce the mortality up to 50%, several key questions yet remained to answer. Indeed, the licensed RV vaccines were found to be less effective in countries of sub-Saharan Africa and Southeast Asia. Therefore, developing next generation RVA vaccines is warranted. VP6 is highly abundant and conserved protein that forms the middle layer of RV particles and was shown to be both antigenic and immunogenic. Although it does not induce neutralizing antibodies, different VP6 preparations were found to induce homologous and cross-reactive immune responses with partial protection from RVA replication. Although the molecular mechanisms are not fully elucidated, VP6-based RVA vaccine candidates are worthy of further consideration. This review aims to focus on different aspects of VP6 protein and its potentiality for an alternative RV vaccine against RV disease.

An emerging novel virus: Atypical porcine pestivirus (APPV)

Abstract: Emerging porcine pestivirus diseases frequently challenge prevention and control strategies in the swine industry. Over the past decade, a few novel pestiviruses have been identified in pigs. This article focuses on the recently emerging atypical porcine pestivirus (APPV) that potentially threatens global swine herd health security. The virus was first identified in 2016, in the United States and thereafter, accumulated evidence shows that it is currently distributed in three continents. The clinical presentation of APPV-infected pigs is characterized by congenital tremor (CT) type A-II in piglets, while adult pigs may become persistent carriers and shedders. Here, a literature review is conducted to summarize the published findings in the virus genomic biology, transmission, epidemiology, pathogenesis, and diagnosis, which would shed light on acceleration of development of anti-APPV strategies.

Marine glycan-based antiviral agents in clinical or preclinical trials.

Abstract: The constant outbreak of diseases caused by viral infections has caused serious harm to human health all over the world. Although many antiviral drugs have been approved for clinical use during the past decade, important issues, such as unsatisfactory efficacy, toxicity, and high cost of drugs, remain unresolved. Glycans are major components of the surfaces of both host cells and most viruses and play critical roles in the steps of viral infection. Marine glycans have more structural diversities than those found in humans. Most importantly, low toxicity and low-cost marine glycans have demonstrated potent antiviral activities through multiple molecular mechanisms. As a result, a series of marine glycan-derived agents are undergoing preclinical and clinical trials. This review discusses the recent progress in research on the marine glycan-based antiviral agents in clinical trials, relating to their structural features and clinical applications. In addition, molecular mechanisms of marine glycans involved in viral infection and novel strategies used in glycan-based drug development are critically reviewed and discussed.

Lessons in diagnostic virology: expected and unexpected sources of error.

Abstract: Viral diagnostics have shown continued innovation, with serological and molecular diagnostic assays pushing the limits of sensitivity. Technology has provided new automated shared diagnostic platforms that reduce hands-on time, while with globalisation of the diagnostic market, commercial assays are applied across epidemiologically diverse settings on different patient and viral populations. However, with these novel developments, new and often unexpected sources of diagnostic error emerge. In this review we will reflect on case studies that highlight these often underappreciated or unexpected diagnostic errors spanning pre-analytical, analytical, and post-analytic processes. We will also suggest approaches that could help identify error and reduce the impact on patient management.

Tat basic domain: A "Swiss army knife" of HIV-1 Tat?

Abstract: Tat (transactivator of transcription) regulates transcription from the HIV provirus. It plays a crucial role in disease progression, supporting efficient replication of the viral genome. Tat also modulates many functions in the host genome via its interaction with chromatin and proteins. Many of the functions of Tat are associated with its basic domain rich in arginine and lysine residues. It is still unknown why the basic domain exhibits so many diverse functions. However, the highly charged basic domain, coupled with the overall structural flexibility of Tat protein itself, makes the basic domain a key player in binding to or associating with cellular and viral components. In addition, the basic domain undergoes diverse posttranslational modifications, which further expand and modulate its functions. Here, we review the current knowledge of Tat basic domain and its versatile role in the interaction between the virus and the host cell.

Rotavirus infections in children in Turkey: A systematic review.

Abstract: We aimed to describe rotavirus epidemiology and clinical findings including extraintestinal manifestations in a setting that has yet to introduce rotavirus vaccines in the national immunization program. A literature search was performed by using the key words "Turkey" and "rotavirus." Ninety-eight studies published between 1987 and 2016 including epidemiological, clinical, and genotypical data at least 1 year duration were included. There were a total of 117 741 children with diarrhea and 26 566 rotavirus gastroenteritis with a median detection rate 31.8% (95% CI, 31.3-32.4) under 5 years of age. The rate of dehydration was 47% (95% CI, 23.4-91.6). There were 328 cases reported to be presenting with a various complication related to rotavirus in 2750 children in eight studies. The overall complication rate was 11.7% (95% CI, 10.7-12.9). The cumulative incidence of the most common genotypical combinations circulating worldwide was only 59.7% (G9[P8], 25%; G1[P8], 22%; G2[P4], 5.6%; G3[P8], 2.6%; G4[P8], 4.5%) whereas mixed, untypeable, and other genotypes were 2.4%, 15%, and 22.9% respectively. Our results point out the importance of rotavirus vaccination by presenting that rotavirus may cause severe complications besides severe gastroenteritis. The role of strain diversity in the variability of clinical presentations of rotavirus infections needs to be further investigated.

Going beyond serology for stratifying the risk of CMV infection in transplant recipients.

Abstract: Knowledge of donor and recipient (D/R) cytomegalovirus (CMV) serostatus is critical for risk stratification of CMV infection and disease in transplant recipients, particularly in the solid organ transplantation (SOT) setting. Despite its broad availability and the success of it use, the risk stratification based on the D/R serostatus is not free of limitations since there are a nondepreciable number of patients that are not accurately categorized by this approach. In fact, up to 20% of seropositive SOT recipients, classically considered at intermediate risk, develop episodes of CMV infection and disease after transplantation. Here, we provide an overview of additional donor and recipient factors that may have utility in identifying patients at risk for post-transplant CMV infection. Specifically, we summarize our current understanding regarding the potential use of use CMV-specific T-cell-mediated immunity, neutralizing antibodies and host genetics that may influence the risk of CMV infection and disease. We provide an overview of the benefits and limitations associated with using these immunological factors in risk stratification and propose specific variables that could be analyzed at the pretransplant evaluation to improve the identification of patients with increased individual susceptibility.

Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy.

Abstract: Phages and bacteria are known to undergo dynamic and co-evolutionary arms race interactions in order to survive. Recent advances from in vitro and in vivo studies have improved our understanding of the complex interactions between phages, bacteria, and the human immune system. This insight is essential for the development of phage therapy to battle the growing problems of antibiotic resistance. It is also pivotal to prevent the development of phage-resistance during the implementation of phage therapy in the clinic. In this review, we discuss recent progress of the interactions between phages, bacteria, and the human immune system and its clinical application for phage therapy. Proper phage therapy design will ideally produce large burst sizes, short latent periods, broad host ranges, and a low tendency to select resistance.

Annexin A2 extracellular translocation and virus interaction: A potential target for antivirus-drug discovery.

Abstract: Annexin A2 is a membrane scaffolding and binding protein, which mediated various cellular events. Its functions are generally affected by cellular localization. In the cytoplasm, they interacted with different phospholipid membranes in Ca2+ -dependent manner and play vital roles including actin binding, remodeling and dynamics, cytoskeletal rearrangement, and lipid-raft microdomain formation. However, upon cell exposure to certain stimuli, annexin A2 translocates to the external leaflets of the plasma membrane where annexin A2 was recently reported to serve as a virus receptor, play an important role in the formation of virus replication complex, or implicated in virus assembly and budding. Here, we review some of annexin A2 roles in virus infections and the potentiality of targeting annexin A2 in the design of novel and promising antivirus agent that may have a broader consequence in virus therapy.