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Central retinal artery occlusion after vaccination with whole virion inactivated SARSCoV- 2 vaccine Covaxin.

Coronavirus disease 2019 (COVID-19) vaccinations have been associated with a higher risk of thromboembolic events. There have been no reports of central retinal artery occlusion (CRAO) after vaccination with the indigenously developed Covaxin, and worldwide, there has been only one such isolated case after administration of the AstraZeneca vaccine. We report a case of a 44-year-old healthy man who presented with sudden painless vision loss in his left eye 10 days after receiving Covaxin. His best-corrected visual acuity was minimal perception of light, with a relative afferent pupillary defect

N6-Methyladenine Modification of Hepatitis Delta Virus Regulates Its Virion Assembly by Recruiting YTHDF1.

Hepatitis delta virus (HDV) is a defective satellite virus that uses hepatitis B virus (HBV) envelope proteins to form its virions and infect hepatocytes via the HBV receptors. Concomitant HDV/HBV infection continues to be a major health problem, with at least 25 million people chronically infected worldwide. N6-methyladenine (m6A) modification of cellular and viral RNAs is the most prevalent internal modification that occurs cotranscriptionally, and this modification regulates various biological processes. We have previously described a wider range of functional roles of m6A methylation of HB…

Флуоресцентный белковый помет аденовальных белков pV и pIX показывает "запоздалый аккумулирующий отсек вирионов".

Человеческий аденовирус типа 5 (HAdV5) вызывает заболевания верхнего и нижнего дыхательных путей. Были подробно изучены первые этапы внедрения HADV5 в репродукцию генома в принимающем ядре. Однако поздние стадии инфицирования по-прежнему плохо понимаются. Здесь мы собрались для того, чтобы прояснить спонтанное оркестрирование последних аденовирусных ядерных реконструаций в живых клетках. Мы создали вирусные мутанты, выражающие флуоресцентно помеченный белок IX (pIX) и белок V (pV) соответственно, капсид и вирусный геном. Мы выяснили, что во время выращивания потомства оба белка попадают в бесм

Совпадение в аннотации оригинала
The human adenovirus type 5 (HAdV5) causes disease of the upper and lower respiratory tract. The early steps of HAdV5 entry up to genome rep … in V (pV), a capsid and viral genome associated protein, respectively. We found that during progeny virion production both proteins localize to a membrane-less, nuclear compartment, which is highly impermeable such that in immunofluorescence microscopy antibodies can hardly penetrate it. We termed this compartment 'late virion accumulation compartment' ( …

Identification of novel antipoxviral agents: mitoxantrone inhibits vaccinia virus replication by blocking virion assembly.

The bioterror threat of a smallpox outbreak in an unvaccinated population has mobilized efforts to develop new antipoxviral agents. By screening a library of known drugs, we identified 13 compounds that inhibited vaccinia virus replication at noncytotoxic doses. The anticancer drug mitoxantrone is unique among the inhibitors identified in that it has no apparent impact on viral gene expression. Rather, it blocks processing of viral structural proteins and assembly of mature progeny virions. The isolation of mitoxantrone-resistant vaccinia strains underscores that a viral protein is the likely …

Virion polypeptide heterogeneity among virulent and avirulent strains of eastern equine encephalitis (EEE) virus.

Comparative analysis of structural virion polypeptides of 24 selected EEE virus strains, representing North and South American types, was performed by one-dimensional discontinuous sodium dodecyl sulfate (SDS)-polyacrylamide-gel electrophoresis (PAGE). The structural proteins of different EEE virus isolates, resolved by this method, exhibited mol.wts. values in the range of 57-60 X 10(3) for (E-1), 51-54 X 10(3) for (E-2) and 35-38 X 10(3) daltons for the core (NP) nucleocapsid. The exception was the South American human lethal virus, TRVL-89287 strain, which was shown to possess only a single…

Virion display reveals MD-1 as an endogenous agonist for the orphan receptor GPRC5B.

One-third of all nonodorant G protein-coupled receptors (GPCRs) in humans are orphans with no known ligands. Deorphanization of these GPCRs is hampered by the difficulty of producing purified receptors in their native conformations and the lack of a proteome-wide, high-throughput screening approach. Here, we validated a generalizable strategy to deorphanize multipass membrane receptors in the human genome. We leveraged virion display technology to produce recombinant viruses that displayed the four orphan receptors in the GPRC5 family and used them as probes against a human proteome array to i…

Structural atlas of Pakpunavirus P7-1 reveals determinants of virion stability and genome ejection.

Bacteriophages of the Pakpunavirus genus exhibit broad host range and potent bacteriolytic activity, making them promising candidates for clinical use. Here, we present a structural atlas of the therapeutic phage Pakpunavirus P7-1, a component of a phage cocktail targeting Pseudomonas aeruginosa that has undergone Phase 1/2 clinical trials. We determined the near-atomic structure of the extended virion and obtained a medium-resolution reconstruction of the contracted tail. Atomic models were built for 20 structural proteins comprising the icosahedral capsid, neck, contractile tail, and basepla…

Piperazine-Substituted Pyranopyridines Exhibit Antiproliferative Activity and Act as Inhibitors of HBV Virion Production.

Advances in medicinal chemistry have led to the development of anticancer and anti-infectious drugs. However, many types of cancer and viral … veral compounds exhibit selective activity against hepatitis B virus by preventing the formation of virion particles. This study led to the identification of a novel class of piperazine-substituted pyranopyridines with antiproliferative activity towards a wide range of tumor cell lines as well as the non-toxic inhibitor of HBV virion production.

Antibody bivalency improves antiviral efficacy by inhibiting virion release independently of Fc gamma receptors.

Across the animal kingdom, multivalency discriminates antibodies from all other immunoglobulin superfamily members. The evolutionary forces conserving multivalency above other structural hallmarks of antibodies remain, however, incompletely defined. Here, we engineer monovalent either Fc-competent or -deficient antibody formats to investigate mechanisms of protection of neutralizing antibodies (nAbs) and non-neutralizing antibodies (nnAbs) in virus-infected mice. Antibody bivalency enables the tethering of virions to the infected cell surface, inhibits the release of virions in cell culture, a…

Coronavirus hemagglutinin-esterase and spike proteins coevolve for functional balance and optimal virion avidity.

Human coronaviruses OC43 and HKU1 are respiratory pathogens of zoonotic origin that have gained worldwide distribution. OC43 apparently emer … CoVs, but reminiscent of that of influenza A viruses. Apparently, general principles fundamental to virion-sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens.

Localization of the Houdinisome (Ejection Proteins) inside the Bacteriophage P22 Virion by Bubblegram Imaging.

UNLABELLED: The P22 capsid is a T=7 icosahedrally symmetric protein shell with a portal protein dodecamer at one 5-fold vertex. Extending ou … t cells. We estimated their copy numbers by quantitative SDS-PAGE as approximately 12 molecules per virion of gp16 and gp7 and 30 copies of gp20. To localize them, we used bubblegram imaging, an adaptation of cryo-electron microscopy in which gaseous bubbles induced in proteins by prolonged irradiation are used to map the proteins' locations. We applied …

The intracellular dynamics of hepatitis B virus (HBV) replication with reproduced virion "re-cycling".

Hepatitis B virus (HBV) is a causative agent of hepatitis. Clinical outcome of hepatitis type B depends on the viral titer observed in the peripheral blood of the patient. In the chronic hepatitis patient, production of HBV virion remains low level. On the other hand, the viral load prominently increases in fulminant hepatitis patient as compared with that in the chronic hepatitis patient. We previously proposed a mathematical model describing the intracellular dynamics of HBV replication. Our model clarified that there are two distinguishable replication patterns of HBV named "arrested" and "…

Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses.

Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cycli…

Long-term immunogenicity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques.

Enterovirus 71 (EV71) has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac) based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 we

Bacterial lipopolysaccharide binding enhances virion stability and promotes environmental fitness of an enteric virus.

Enteric viruses, including poliovirus and reovirus, encounter a vast microbial community in the mammalian gastrointestinal tract, which has been shown to promote virus replication and pathogenesis. Investigating the underlying mechanisms, we find that poliovirus binds bacterial surface polysaccharides, which enhances virion stability and cell attachment by increasing binding to the viral receptor. Additionally, we identified a poliovirus mutant, VP1-T99K, with reduced lipopolysaccharide (LPS) binding. Although T99K and WT poliovirus cell attachment, replication, and pathogenesis in mice are eq…

Aberrant virion assembly and limited glycoprotein C production in varicella-zoster virus-infected neurons.

Highly pure (>95%) terminally differentiated neurons derived from pluripotent stem cells appear healthy at 2 weeks after infection with varicella-zoster virus (VZV), and the cell culture medium contains no infectious virus. Analysis of the healthy-appearing neurons revealed VZV DNA, transcripts, and proteins corresponding to the VZV immediate early, early, and late kinetic phases of replication. Herein, we further characterized virus in these neuronal cells, focusing on (i) transcription and expression of late VZV glycoprotein C (gC) open reading frame 14 (ORF14) and (ii) ultrastructural featu

Structure of hepatitis E virion-sized particle reveals an RNA-dependent viral assembly pathway.

Hepatitis E virus (HEV) induces acute hepatitis in humans with a high fatality rate in pregnant women. There is a need for anti-HEV research to understand the assembly process of HEV native capsid. Here, we produced a large virion-sized and a small T=1 capsid by expressing the HEV capsid protein in insect cells with and without the N-terminal 111 residues, respectively, for comparative structural analysis. The virion-sized capsid demonstrates a T=3 icosahedral lattice and contains RNA fragment in contrast to the RNA-free T=1 capsid. However, both capsids shared common decameric organization. T…

Trillion virion delay: time from testing positive for HIV to presentation for primary care.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals' initial presentation to medical care frequently occurs at a point of advanced immunosuppression. OBJECTIVES: To investigate the time between HIV testing and presentation to primary care. Also to examine factors associated with delayed presentation. METHODS: One hundred eighty-nine consecutive outpatients without prior primary care for HIV infection were assessed at 2 urban hospitals: Boston City Hospital, Boston, Mass, and Rhode Island Hospital, Providence. Sociodemographics, alcohol and drug use, social support, sexual bel

Recombinant and virion-derived soluble and particulate immunogens for vaccination against tick-borne encephalitis.

Using different forms of the envelope glycoprotein E from tick-borne encephalitis virus we investigated the influence of physical and antigenic structure on the efficacy of vaccination. Different protein E-containing preparations were either derived from purified virions or were produced as recombinant proteins in COS cells. These included soluble dimeric forms (virion-derived protein E dimers with and without membrane anchor; recombinant protein E dimers without membrane anchor), micellar aggregates of protein E (rosettes), and recombinant subviral particles (RSPs). The structural differences…

Virion transcriptase activity of rimantadine-sensitive and rimantadine-resistant variants of human influenza virus.

All rimantadine-resistant variants of influenza virus prepared by consecutive passages in the presence of rimantadine had increased virion transcriptase activity as compared to the original strains. The increased virion transcriptase activity of rimantadine-resistant strains was unrelated to the possible role of M1 protein, since RNPs isolated from the virions of these variants also revealed higher transcriptase activity as compared to RNPs isolated from rimantadine-sensitive virus. The study of rimantadine-resistant recombinant X-4 which inherited from the resistant fowl plague virus (FPV) on…