Virus-specific Proteins Research Articles

Papel do citomegalovírus humano (HCMV) na oncomodulação de tumores cerebrais

O citomegalovírus Humano (HCMV) é um agente viral queacomete indivíduos imunocomprometidos e recém nascidos,causando uma variedade de doenças graves e podendo levar ao óbito. Recentes evidências indicam que o HCMV está envolvido no processo de progressão tumoral. Estudos demonstraram que o DNA viral e proteínas virais estão presentes em diferentes tipos de câncer; proteínas virais são capazes de interferir com a progressão do ciclo celular, apoptose e ativação do sistema imune e há indicações de que a infecção de células tumorais pelo HCMV aumenta a malignidade das mesmas. Estas descobertas levaram à criação do termo oncomodulação, definido como a habilidade do vírus em promover um processo tumoral. Os estudos do papel do HCMV no processo de malignidade de tumores estão avançando enormemente e um melhor entendimento do fenômeno de oncomodulação éessencial para elucidação da participação do HCMV na progressão de tumores e para determinação de proteínas virais que podem ser alvo terapêutico em certos tipos de cânceres. Esta revisão discute os mecanismos envolvidos na oncogênese e oncomodulação de gliomas malignos promovidas pelo HCMV.

Repurposing Fendiline as a novel anti‐viral therapeutic

The most prolonged and fatal outbreak of the Ebola virus (EBOV) occurred in 2014, claiming the lives of thousands. Although more than 40 years have passed since the initial discovery of EBOV, there are still no available treatments with FDA approval. Clinical case studies from human survivors highlighted that a hallmark of survival is a measurable immune response against specific viral proteins, such as VP40. VP40, is the canonical mediator of EBOV budding. Therefore, slowing down viral propagation through inhibiting replication, trafficking or budding could be the key to developing an efficacious treatment.VP40 interacts with host proteins and lipids to oligomerize at the plasma membrane (PM) to form the filamentous structure of the virus. The initial association between VP40 and the PM is through electrostatic and stereospecific interactions with phosphatidyl serine (PS). Following PM docking, VP40 filamentous oligomerization is also dependent upon the presence of PS at the PM. These filaments are the building block for nascent viral particles, which will ultimately bud from the cell to propagate the virus within the host. Therefore, PS within the inner leaflet of the PM is essential for viral budding and propagation. Moreover, VP40's ability to produce virus like particles (VLPs) when expressed in mammalian cells, even in the absence of the other viral proteins, allows EBOV budding to be studied in a BSL‐2 setting.Fendiline, an FDA approved drug for coronary heart disease, has been shown to significantly reduce PS from the PM. Therefore, this project focuses on repurposing Fendiline as a novel anti‐viral therapy to inhibit EBOV budding. We hypothesized that treating HEK 293 with Fendiline, would reduce VP40's ability to bind to the PM, oligomerize, and ultimately inhibit VLP production.To monitor Fendiline's effect on PS in HEK293 cells, live cell confocal imaging experiments were performed on HEK 293 cells expressing the high affinity PS probe, GFP‐LactC2. After 48 hours of treatment, 5 uM Fendiline significantly reduced GFP‐LactC2 localization at the PM by ~25% (p=0.03). Lipidomic analysis of HEK 293 cells also revealed a significant reduction in total cellular levels of PS after 48 hours of 5 uM treatment (~30%, p=0.03). To assess the effect of Fendiline on VP40 binding to the PM, HEK 293 cells expressing GFP‐VP40 were treated with Fendiline and monitored for 48 hours. Again, after 48 hours of 5 uM treatment, there was a significant reduction of GFP‐VP40 localization to the PM (~15%, p=0.0001). Functional budding assays were performed to assess the effect of Fendiline on VLP production. After 48 hours, 5 uM Fendiline reduced VLP production by ~60% (p=0.025). Scanning electron microscopy experiments revealed a significant reduction in filamentous particle length and density after 48 hours of 1 uM or 5 uM Fendiline treatment compared to untreated cells expressing FLAG‐VP40(p<0.01).Our project has highlighted that repurposing drugs such as Fendiline and targeting lipid metabolism are promising avenues for developing anti‐viral therapies. The next stop for this project is to extend the studies into live virus models in a BSL‐4 setting.Support or Funding InformationThis work has been supported by NIH training grant T32GM075762 and NIH AI081077This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hsp90 interacts with multiple dengue virus 2 proteins

Infections with the mosquito-borne dengue virus (DENV) remain a significant public health challenge. In the absence of a commercial therapeutic to treat DENV infection, a greater understanding of the processes of cellular replication is required. The abundant cellular chaperone protein heat shock protein 90 (Hsp90) has been shown to play a proviral role in the replication cycle of several viruses, predominantly through the stabilization of specific viral proteins. To investigate any potential role of Hsp90 in DENV infection the interaction between Hsp90 and DENV proteins was determined through co-immunoprecipitation experiments. Six DENV proteins namely envelope (E) and nonstructural (NS) proteins NS1, NS2B, NS3, NS4B and NS5 were shown to interact with Hsp90, and four of these proteins (E, NS1, NS3 and NS5) were shown to colocalize to a variable extent with Hsp90. Despite the extensive interactions between Hsp90 and DENV proteins, inhibition of the activity of Hsp90 had a relatively minor effect on DENV replication, with inhibition of Hsp90 resulting in a decrease of cellular E protein (but not nonstructural proteins) coupled with an increase of E protein in the medium and an increased virus titer. Collectively these results indicate that Hsp90 has a slight anti-viral effect in DENV infection.

Detection of human papillomavirus in oral mucosa

Introduction: According to the National Cancer Institute (INCA) 2017, Brazil shows high prevalence rates in malignant neoplasms with primary localization in the oral cavity, since oral cancer affects the lips and oral cavity. It is a multifactorial disease, derived from genetic, environmental or infectious factors (viruses) isolated or in association, causing cytogenetic changes that proceed through a somatic mutation sequence, resulting in uncontrolled cell proliferation. Objective: To study the detection of human papillomavirus (HPV) in the oral mucosa, making it possible to trace possible risk factors associated with its development. Methods: This is a descriptive cross-sectional study of the bibliographic review on the subject, monographs, dissertations, theses and books, comparatively analyzing the information from these research sources, making a discussion about the results of this survey. Results and Discussion: There are more than 100 types of papillomavirus identified, 24 of these related to the oral cavity. Transmission of papillomavirus to oral mucosa occurs by self-inoculation and through the practice of oral sex. Papillomavirus infection begins when the virus contacts the basal epithelial cells by a slow process of endocytosis, from the binding to a specific receptor on the surface of basal cells. Viral tropism is caused in part by the binding of specific viral surface proteins to certain host cell surface receptor proteins. Studies to detect the presence of papillomavirus in the oral mucosa reveal that this virus appears to persistently or frequently infect the mouth, including in children and adolescents. Conclusion: Detection rates vary mainly according to the population studied and the sensitivity of the methods used, with the main types of papillomavirus being found, Papillomavirus 16 and 18.

The French Armed Forces Virology Unit: A Chronological Record of Ongoing Research on Orthopoxvirus.

Since the official declaration of smallpox eradication in 1980, the general population vaccination has ceased worldwide. Therefore, people under 40 year old are generally not vaccinated against smallpox and have no cross protection against orthopoxvirus infections. This naïve population may be exposed to natural or intentional orthopoxvirus emergences. The virology unit of the Institut de Recherche Biomédicale des Armées (France) has developed research programs on orthopoxviruses since 2000. Its missions were conceived to improve the diagnosis capabilities, to foster vaccine development, and to develop antivirals targeting specific viral proteins. The role of the virology unit was asserted in 2012 when the responsibility of the National Reference Center for the Orthopoxviruses was given to the unit. This article presents the evolution of the unit activity since 2000, and the past and current research focusing on orthopoxviruses.

Do Viruses Exchange Genes across Superkingdoms of Life?

Viruses can be classified into archaeoviruses, bacterioviruses, and eukaryoviruses according to the taxonomy of the infected host. The host-constrained perception of viruses implies preference of genetic exchange between viruses and cellular organisms of their host superkingdoms and viral origins from host cells either via escape or reduction. However, viruses frequently establish non-lytic interactions with organisms and endogenize into the genomes of bacterial endosymbionts that reside in eukaryotic cells. Such interactions create opportunities for genetic exchange between viruses and organisms of non-host superkingdoms. Here, we take an atypical approach to revisit virus-cell interactions by first identifying protein fold structures in the proteomes of archaeoviruses, bacterioviruses, and eukaryoviruses and second by tracing their spread in the proteomes of superkingdoms Archaea, Bacteria, and Eukarya. The exercise quantified protein structural homologies between viruses and organisms of their host and non-host superkingdoms and revealed likely candidates for virus-to-cell and cell-to-virus gene transfers. Unexpected lifestyle-driven genetic affiliations between bacterioviruses and Eukarya and eukaryoviruses and Bacteria were also predicted in addition to a large cohort of protein folds that were universally shared by viral and cellular proteomes and virus-specific protein folds not detected in cellular proteomes. These protein folds provide unique insights into viral origins and evolution that are generally difficult to recover with traditional sequence alignment-dependent evolutionary analyses owing to the fast mutation rates of viral gene sequences.

Anti-HERV-K (HML-2) capsid antibody responses in HIV elite controllers

BackgroundHuman endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.ResultsWe developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on the matrix (peptides 16 and 31), one on p15 (peptide 85), three on the capsid (peptides 81, 97 and 117), one on the nucleocapsid (peptide 137) and one on the QP1 protein (peptide 157). Four epitopes (peptides 16, 31, 85 and 137) were highly immunogenic. No significant differences in antibody responses were found between HIV infected participants (n = 40) and uninfected donors (n = 40) for 6 out of the 8 epitopes tested. The antibody response against nucleocapsid (peptide 137) was significantly lower (p < 0.001), and the response to QP1 (peptide 157) significantly higher (p < 0.05) in HIV-infected adults compared to uninfected individuals. Among those with HIV infection, the level of response against p15 protein (peptide 85) was significantly lower in untreated individuals controlling HIV (“elite” controllers) compared to untreated non-controllers (p < 0.05) and uninfected donors (p < 0.05). In contrast, the response against the capsid protein (epitopes 81 and 117) was significantly higher in controllers compared to uninfected donors (p < 0.001 and <0.05 respectively) and non-controllers (p < 0.01 and <0.05). Peripheral blood mononuclear cells (PBMCs) from study participants were tested for responses against HERV-K (HML-2) capsid recombinant peptide in gamma interferon (IFN-γ) enzyme immunospot (Elispot) assays. We found that the HERV-K (HML-2) Gag antibody and T cell response by Elispot were significantly correlated.ConclusionsHIV elite controllers had a strong cellular and antibody response against HERV-K (HML-2) Gag directed mainly against the Capsid region. Collectively, these data suggest that anti-HERV-K (HML-2) antibodies targeting capsid could have an immunoprotective effect in HIV infection.

A Study to Assess the Effect of Health Teaching Programme on Knowledge Regarding Hepatitis a among Food Handlers Who Residing in Anand District

Hepatitis A, A Term First Introduced In 1967, Is Known To Be A Liver Infection Caused By Hepatitis A Virus (HAV) Whose Primary Replication Site Is In The Hepatocytes (Krugman Et Al.., 1967). HAV Is A Positive Sense, Single Stranded RNA Virus That Belongs To The Family Of Picornavaridae And Is The Unique Member Of The Genus Hepato Virus. Unlike The Other Member Of Family, HAV Requires A Long Adaptation Period To Grow In Cell Culture, Replicates Slowly And Rarely Produces A Cytopathic Effect (Cromeans Et Al., 1987; Lemon 1992) African Green Monkey Kidney Cells Or Fetal Rhesus Kidney Cells Are Commonly Used For Culturing The Virus Although Many Different Cell Types Are Suitable. The Genome Of The HAV Is Approximately 7.5 Kb, Consists Of A Highly Conserved 5’ End Non Translated Region (NTR) And Has A Covalently Linked Virus Specific Protein Instead Of A Cap Structure. Hepatitis A Suspected When A Person Gives The History Of Fever, Headache, Myalgia, Photophobia, Chills, Malaise, Nausea, And Anorexia And Epigastric Pain For 4 To 5 Days. It Is Since Turned Afebrile And Now Passes Dark Colored Urine And Clay Colored Stools. He Complains Of Generalized Itching. His Eyes, Tounge, Nail And Later Whole Body Are Yellowish. On Physical Examination Of The Patient, Jaundice, Tender And Enlarged Liver, And Some Time Lymphadenopathy Are Found. Laboratory Investigation Reveal Serum Bilirubin Of 1 Mg % Or More (Normal,0.3 To 0.5 Mg %) And Aspartate Aminotransferase And Alanine Aminotransferase Levels Of 300 IU/L (Normal 5 To 30 IU/L). The Diagnosis Is Confirmed By Demonstrating, In Paired Sera, A Rising Titer Of Anti-HA Antibodies. HA Is A Benign Condition. After 2 To 3 Weeks Of Illness And A Prolonged Convalescence Recovery Occurs.

Combination CpG and MPL agonists heighten vaccine-induced protection against Influenza A virus challenge

Abstract Current strategies for Influenza A Virus (IAV) vaccination result in antibodies against strain specific viral coat proteins. These antibodies do not provide protection against heterologous IAV strains and leave the population vulnerable to pandemics of highly pathogenic IAV. Vaccines may be improved by targeting T cells, which unlike B cells, are able to recognize inner, conserved IAV antigens, such as nucleoprotein (NP), increasing the potential for protection against different IAV stains. During live IAV infection multiple pattern recognition receptors (PRRs) on innate immune cells are activated; therefore vaccines triggering multiple PRRs may elicit better protection. As dendritic cells are the most potent antigen presenting cells for T cells, bone marrow derived dendritic cells (BMDCs) were activated by combined agonists that trigger separate, yet complementary PRR signaling pathways. Here we show that combined PRR agonists MPL and CpG, which activate TLR4 and TLR9 respectively, increased in vitro cytokine and chemokine expression by BMDCs. Further, intramuscular vaccination of mice with IAV pdm09 H1N1 hemagglutinin (HA) protein plus combined CpG and MPL, as adjuvants, induced the formation of pdm09 HA specific IgG2c antibodies. Combined CpG and MPL recipient mice experienced less weight loss and lower mortality after lethal challenge with pdm09 H1N1 compared to mice receiving lone agonists, suggesting that combined agonists improve protection. T cell activation in response to combined CpG and MPL is currently being investigated, as well as responses generated via mucosal, intranasal vaccination. Thus combined agonists that promote B and T cell mediated immunity could be incorporated into next generation IAV vaccines.

Investigation of relationship between EBNA-1 expression level and specific foreign protein productivity in transient gene expression of HEK293 cells

Abstract In an attempt to determine the relationship between the Epstein–Barr virus nuclear antigen-1 (EBNA-1) expression level and specific foreign protein productivity (qp), EBNA-1-amplifed HEK293 cells, which achieved a higher EBNA-1 expression level than that achieved by HEK293E cells, were established using dihydrofolate reductase (dhfr)-mediated gene amplification. Compared with a control culture in a null pool, Fc-fusion protein production by transient transfection in the EBNA-1-amplified pool showed a significant improvement. qp was linearly correlated with the EBNA-1 expression level in the transient transfection of EBNA-1-amplified clones, as indicated by the correlation coefficient (R2 = 0.7407). The Fc-fusion protein production and qp in a transient gene expression-based culture with EBNA-1-amplified HEK293 cells, E-amp-68, were approximately 2.0 and 3.2 times, respectively, higher than those in a culture with HEK293E cells. The increase in qp by EBNA-1 amplification mainly resulted from an enhancement in the amount of replicated DNA and level of mRNA expression but not an improved transfection efficiency. Taken together, it was found that EBNA-1 amplification could improve the therapeutic protein production in an HEK293 cell-based transient gene expression system.

Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes.

The first line of defense against viral infections is the innate immune response. Viruses are recognized by pathogen recognition receptors, such as the RIG-I like receptor family, that activate a signaling cascade that induces IFN production. In the present study, we visualized, for the first time in cells, both in overexpression and endogenous levels, complexes formed among key proteins involved in this innate immune signaling pathway. Through different techniques we were able to analyze how these proteins are distributed and reorganized spatially within the cell in order to transmit the signal, leading to an efficient antiviral state. In addition, this work presents a new means by how, when, and where viral proteins can target these pathways and act against the host immune system in order to counteract the activation of the immune response.

Newer direct-acting antivirals for hepatitis C virus infection: Perspectives for India.

Approximately three per cent of the world's population (170-200 million people) is chronically infected with hepatitis C virus (HCV) and almost 500,000 people die each year (mostly in lower middle-income countries) from complications secondary to HCV infection. In India, HCV infection imposes a considerable burden of mortality, morbidity and healthcare costs. In the last two decades, the treatment of HCV has evolved from interferon (IFN)-based therapies with or without ribavirin (RBV) to pegylated-IFN (PEG-IFN) and RBV-based therapies that were better tolerated by patients. However, the introduction of oral drugs, which specifically target virus-specific proteins, has now revolutionized the treatment of chronic HCV. These agents are known as direct-acting antivirals (DAAs). These drugs have resulted in very high HCV cure rates even with reduced treatment duration and an excellent tolerability by the patients compared to PEG-IFN- and RBV-based therapies. In India, sofosbuvir (SOF), one of the most effective DAAs, has been made available at a compassionate price; thus only those DAA-based management strategies, which contain SOF are adopted in India. Here, we review different DAAs and their possible roles in different genotypes and stages of liver disease, stressing upon the role of SOF. An attempt has also been made to devise strategies using SOF for the most prevalent genotypes in our country (genotypes 3 and 1) and cirrhosis.

Quantitative Analysis of the Microtubule Interaction of Rabies Virus P3 Protein: Roles in Immune Evasion and Pathogenesis.

Although microtubules (MTs) are known to have important roles in intracellular transport of many viruses, a number of reports suggest that specific viral MT-associated proteins (MAPs) target MTs to subvert distinct MT-dependent cellular processes. The precise functional importance of these interactions and their roles in pathogenesis, however, remain largely unresolved. To assess the association with disease of the rabies virus (RABV) MAP, P3, we quantitatively compared the phenotypes of P3 from a pathogenic RABV strain, Nishigahara (Ni) and a non-pathogenic Ni-derivative strain, Ni-CE. Using confocal/live-cell imaging and dSTORM super-resolution microscopy to quantify protein interactions with the MT network and with individual MT filaments, we found that the interaction by Ni-CE-P3 is significantly impaired compared with Ni-P3. This correlated with an impaired capacity to effect association of the transcription factor STAT1 with MTs and to antagonize interferon (IFN)/STAT1-dependent antiviral signaling. Importantly, we identified a single mutation in Ni-CE-P3 that is sufficient to inhibit MT-association and IFN-antagonist function of Ni-P3, and showed that this mutation alone attenuates the pathogenicity of RABV. These data provide evidence that the viral protein-MT interface has important roles in pathogenesis, suggesting that this interface could provide targets for vaccine/antiviral drug development.

Phosphorylation-Mediated Interaction of Hepatitis C Virus NS5A and the Cellular YB-1 Controls HCV Propagation and the Early Stage of Viral RNA Replication

About 130-150 million individuals worldwide are chronically infected by hepatitis C virus (HCV); HCV infection has become a leading cause of liver cirrhosis and hepatocellular carcinoma. The HCV life cycle relies on the cooperation of specific viral proteins and various cellular factors. The cellular protein Y-box binding protein 1 (YB-1) has recently been identified as a HCV host cofactor; however, its mechanism has not been fully characterized. The HCV nonstructural protein NS5A plays critical roles in almost every stage of HCV propagation, and has been proposed to control the switch between the defined stages of the HCV life cycle. Moreover, NS5A has recently emerged as a target for the development of novel anti-HCV drugs. Our studies have found that YB-1 not only interacts with NS5A, but also protects NS5A from degradation. Furthermore, both the NS5A/YB-1 interaction and the NS5A-stabilizing activity of YB-1 are dependent on the phosphorylation of YB-1 at serine 102 (S102). Interestingly, the YB-1 S102 site has previously been reported to be phosphorylated by Akt, which is in turn activated by HCV infection. Our study also reveals that DDX3, an YB-1-interacting partner, is another NS5A-binding protein, which plays a different role than YB-1 in HCV RNA replication and infectious virus production. Taken together, the elucidation of YB-1 participation in the HCV life cycle has led to a proposed mechanism of efficient virus propagation via coordination of the different stages of the viral life cycle through controlling stage-wise switches in the viral life cycle. Our finding also provides a novel niche for designing strategies for the development of new anti-HCV drugs by blocking specific virus-host interactions.

Spectrum of produced GAG gene viral proteins in lymphocytes infected HIV-1 NL4-3 strains in vitro

Aim. To study spectrum of viral proteins secreted into the culture medium by the healthy donor peripheral blood lymphocytes infected by HIV-1 NL4-3 strain in vitro.Methods. We used a primary lymphocytes culture obtained from healthy donors. For synchronous infection of primary lymphocytes culture in vitro NL4-3 strain of human immunodeficiency virus (HIV) (NIH AIDS Research &amp; Reference Reagents Program, USA) was used. The HIV-1 titer in the supernatants was determined by enzyme immunoassay (EIA p24gag Coulter). In addition, electrophoresis of clarified culture medium proteins in 12.5% polyacrylamide gel under denaturing conditions followed by electron transport onto a nitrocellulose membrane; immunoblotting for detection of virus-specific proteins using positive control serum to HIV-1 («Bio-Rad») were performed; protein markers kits LMW 94-14.4 kD, HMW 212-53 kD («Pharmacia Biotech») were used to determine the seroactive fractions molecular weight.Results.. HIV antigens spectrum in the culture medium was studied on the 4th, 9th and 13th days after lymphocyte culture infection with HIV. Within 13 days of virus reproduction both non-structural and structural proteins of HIV-1 gag gene are detected in the culture medium, spectrum and quantitative range of which varies with time. After 4 hours of HIV reproduction in primary lymphocytes culture in vitro large number of gag gene nonstructural proteins (p40, p55) are exported from cells into culture medium. Further, gag gene non-structural proteins may be cleaved into the structural proteins (p24/25, R18) under the cellular proteases action, which is caused by the proteolytic enzymes accumulation in the culture medium.Conclusion. In HIV reproduction in primary lymphocytes cultures soluble forms of the HIV-1 gag gene proteins are secreted into culture medium; in the initial stages of the infection HIV proteins spectrum in the culture medium of lymphocytes activated with phytohemagglutinin in vitro consists of only the HIV-1 precursor proteins (p55, p40) and at a later stages - also of the gag gene viral capsid proteins (p24/25, R18).

A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection

BackgroundDengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Aedes aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated. Ubiquitin proteins have multiple functions in insects, including marking proteins for proteasomal degradation, regulating apoptosis and mediating innate immune signaling. MethodsWe used qRT-PCR to quantify gene expression and infection, and RNAi to reduce Ub3881 expression. Mosquitoes were infected with DENV through blood feeding. We transfected DENV protein expression constructs to examine the effect of Ub3881 on protein degradation. We used site-directed mutagenesis and transfection to determine what amino acids are involved in Ub3881-mediated protein degradation. Immunofluorescence, Co-immunoprecipitation and Western blotting were used to examine protein interactions and co-localization. ResultsThe overexpression of Ub3881, but not related ubiquitin proteins, decreased DENV infection in mosquito cells and live Ae. aegypti. The Ub3881 protein was demonstrated to be involved in DENV envelope protein degradation and reduce the number of infectious virions released. ConclusionsWe conclude that Ub3881 has several antiviral functions in the mosquito, including specific viral protein degradation. General significanceOur data highlights Ub3881 as a target for future DENV prevention strategies in the mosquito transmission vector.

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Canine parvovirus (CPV) leads to an acute disease, characterized by hemorrhagic gastroenteritis, vomiting and myocarditis in dogs. The disease can affect dogs of any age but is fatal in pups. CPV has undergone genetic variations that have led to emergence of various CPV-2 antigenic variants such as 2a, 2b and 2c with replacement of the original CPV-2 circulating in the dog population. CPV genome is made up of 5.2 Kb nucleotides. Viral protein VP2 plays a very important role in determining antigenicity and host range specificity of CPV. The antigenicity as well as host range of CPV is determined by virus specific VP2 protein. That’s why the mutations that affect the VP2 gene are the main source of different antigenic variants. It spreads rapidly in the wild population of canines as well as domestic animals, infected feces serve as a main source of infection because the virus is shed in large quantity in the feces particularly 4 - 7 days post infection. The present review is focused on various

Human metapneumovirus small hydrophobic (SH) protein downregulates type I IFN pathway signaling by affecting STAT1 expression and phosphorylation

Type I interferon (IFN) is a key mediator of antiviral immunity. Human metapneumovirus (HMPV) inhibits IFN signaling, but does not encode homologues of known IFN antagonists. We tested the hypothesis that a specific viral protein prevents type I IFN signaling by targeting signal transducer and activator of transcription-1 (STAT1). We found that human airway epithelial cells (capable of expressing IFNs) became impaired for STAT1 phosphorylation even without direct infection due to intrinsic negative feedback. HMPV-infected Vero cells (incapable of expressing IFN) displayed lower STAT1 expression and impaired STAT1 phosphorylation in response to type I IFN treatment compared to mock-infected cells. Transient overexpression of HMPV small hydrophobic (SH) protein significantly inhibited STAT1 phosphorylation and signaling, and recombinant virus lacking SH protein was unable to inhibit STAT1 phosphorylation. Our results indicate a role for the SH protein of HMPV in the downregulation of type I IFN signaling through the targeting of STAT1.

VIP in HIV Diarrhea: Finding Links for the "Slim Disease".

Diarrhea, in the context of human immunodeficiency virus (HIV) infection, is an enormously important clinical issue (Smith et al., 1988). Diarrhea in patients with AIDS is extremely problematic for both patient and clinician. More than 50% of AIDS patients suffer from diarrhea, the cause of which is unexplained in most of the cases. The causes of diarrhea in HIV infection are multifactorial. Chiefly, these may be caused by the primary retroviral infection per se, several opportunistic infections, alteration of gut microbiome, immune reconstitution, water sanitation or as a complication of highly active anti-retroviral therapy (HAART) like didanosine or ritonavir, and may also result from induced pancreatic insufficiency (Haas et al., 2011; Saha et al., 2011; Murray and Rubio-Tapia, 2012; Vyas et al., 2012; Agholi et al., 2013; Martin et al., 2013; Clay and Crutchley, 2014; Dye, 2014; Dikman et al., 2015; Green et al., 2015; Rubaihayo et al., 2015; Yates et al., 2015). The diarrhea in primary HIV infection is primarily secretory in nature (Juckett and Trivedi, 2011; MacArthur and DuPont, 2012). Some preliminary studies have suggested the role of viral proteins in causation and aggravation of diarrhea in HIV infected patients. For example, retroviral tat proteins have been demonstrated to enhance myenteric neuronal excitability by altering different sodium channels (Ngwainmbi et al., 2014). It is obvious that in HIV infection, a viral specific protein that affects genomic transcription would affect diverse cellular mechanism (s). This opinion piece advances a concept of how HIV may gain entry into the gastrointestinal mucosa using an upstream neuropeptide mechanism, providing a perspective of an incipient mechanism involved in mucosal disease caused by HIV and potential druggable targets for HIV induced diarrhea.

L Particles Transmit Viral Proteins from Herpes Simplex Virus 1-Infected Mature Dendritic Cells to Uninfected Bystander Cells, Inducing CD83 Downmodulation.

Mature dendritic cells (mDCs) are known as the most potent antigen-presenting cells (APCs) since they are also able to prime/induce naive T cells. Thus, mDCs play a pivotal role during the induction of antiviral immune responses. Remarkably, the cell surface molecule CD83, which was shown to have costimulatory properties, is targeted by herpes simplex virus 1 (HSV-1) for viral immune escape. Infection of mDCs with HSV-1 results in downmodulation of CD83, resulting in reduced T cell stimulation. In this study, we report that not only infected mDCs but also uninfected bystander cells in an infected culture show a significant CD83 reduction. We demonstrate that this effect is independent of phagocytosis and transmissible from infected to uninfected mDCs. The presence of specific viral proteins found in these uninfected bystander cells led to the hypothesis that viral proteins are transferred from infected to uninfected cells via L particles. These L particles are generated during lytic replication in parallel with full virions, called H particles. L particles contain viral proteins but lack the viral capsid and DNA. Therefore, these particles are not infectious but are able to transfer several viral proteins. Incubation of mDCs with L particles indeed reduced CD83 expression on uninfected bystander DCs, providing for the first time evidence that functional viral proteins are transmitted via L particles from infected mDCs to uninfected bystander cells, thereby inducing CD83 downmodulation. HSV-1 has evolved a number of strategies to evade the host's immune system. Among others, HSV-1 infection of mDCs results in an inhibited T cell activation caused by degradation of CD83. Interestingly, CD83 is lost not only from HSV-1-infected mDCs but also from uninfected bystander cells. The release of so-called L particles, which contain several viral proteins but lack capsid and DNA, during infection is a common phenomenon observed among several viruses, such as human cytomegalovirus (HCMV), Epstein-Barr virus, and HSV-1. However, the detailed function of these particles is poorly understood. Here, we provide for the first time evidence that functional viral proteins can be transferred to uninfected bystander mDCs via L particles, revealing important biological functions of these particles during lytic replication. Therefore, the transfer of viral proteins by L particles to modulate uninfected bystander cells may represent an additional strategy for viral immune escape.