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Evasion of CARD8 activation during HIV-1 assembly.

As intracellular parasites, viruses must devise sophisticated mechanisms to produce and assemble viral components while suppressing activation of innate immune effectors. Here, we report that coordination of HIV-1 assembly by the viral polyprotein Gag suppresses inappropriately timed protease (PR) activity to evade the PR activity sensor, caspase recruitment domain-containing protein 8 (CARD8). Using mutants of Gag, we show that disruption of domains controlling viral assembly site [matrix (MA)] or virus particle release (nucleocapsid and p6) leads to premature activation of PR and the CARD8 i…

The ex vivo infection model of the peripheral bovine mononuclear cells (PBMCs) and the bovine spleen cells with the bovine coronavirus (BCoV) induced a differential expression of the host cytokine genes profiles and modulates the virus replication.

The adaptive immune response during BCoV infection of peripheral blood mononuclear cells (PBMCs), the bovine spleen cells, and their isolated T lymphocytes was not studied well. Our study confirmed successful BCoV infection in PBMCs and spleen T cells. The BCoV replication was evidenced by measuring genome copy numbers using real-time PCR and expression levels of BCoV spike and nucleocapsid proteins via western blot and immunofluorescence assays. In infected PBMCs, CD4 T-cell levels were 1.45-fold higher, and CD8 T-cell levels were 1.6-fold lower compared to sham-infected cells. Conversely, in…

Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors.

People living with human immunodeficiency virus (HIV) receiving integrase strand transfer inhibitors (INSTIs) have been reported to experience virological failure in the absence of resistance mutations in integrase. To elucidate INSTI resistance mechanisms, we propagated HIV-1 in the presence of escalating concentrations of the INSTI dolutegravir. HIV-1 became resistant to dolutegravir by sequentially acquiring mutations in the envelope glycoprotein (Env) and the nucleocapsid protein. The selected Env mutations enhance the ability of the virus to spread via cell-cell transfer, thereby increasi…

Neutralizing and binding antibody responses to SARS-CoV-2 with hybrid immunity in pregnancy.

Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies … gh infection. Both vaccination and infection-induced anti-RBD IgA, which was more durable than anti-nucleocapsid IgA. IgA response was attenuated in pregnancy compared to non-pregnant controls. These data provide additional evidence of augmentation of humoral immune responses in hybrid immunity in pregnancy.

Resilience and Beyond the Acute Phase Challenges: Case Series on Prolonged COVID-19 Infection in Immunocompromised Individuals.

BACKGROUND: COVID-19 infection is associated with an increased risk of severe illness and adverse outcomes in individuals with immunocomprom … cohort demonstrated positive anti-receptor binding-domain immunoglobulin G (IgG) and negative anti-nucleocapsid IgG values. CONCLUSION: Persistent COVID-19 infection should be considered in the differential diagnosis of immunocompromised patients who exhibit ongoing symptoms or lack of improvement in chest X-ray findings following initial COVID-19 treatment. …

Factors associated with IgG titers against SARS-CoV-2 spike protein after second vaccination in people living with HIV controlled with anti-retroviral therapy.

OBJECTIVE: This study aimed to identify factors associated with the response to the SARS-CoV-2 vaccine in people living with HIV (PLWH). METHODS: This study was conducted at the Jikei University School of Medicine, Tokyo, Japan. IgG antibodies against spike and nucleocapsid proteins were detected using Abbott SARS-CoV-2 IgG II Quant assays. RESULTS: During the investigation period, 371 PLWH were enrolled in this study. PLWH with previous COVID-19 infection, untreated or poorly controlled HIV infection, and those whose blood samples were obtained within less than seven days after the second v…

Unmasking an Allosteric Binding Site of the Papain-like Protease in SARS-CoV-2: Molecular Dynamics Simulations of Corticosteroids.

To date, mechanistic insights into many clinical drugs against COVID-19 remain unexplored. Dexamethasone, a corticosteroid, is one of them. While treating the entire corticosteroid database, including vitamins D2 and D3, with cutting-edge computational techniques, several intriguing results are unfolded. From the top-notch candidates, dexamethasone is likely to inhibit the viral main protease (Mpro), with vitamin D3 exhibiting multitarget [Mpro, papain-like protease (PLpro), and nucleocapsid protein (N-pro)] roles and ciclesonide's dynamic flipping disinterring a cryptic allosteric site in the…

The Ebola virus VP40 matrix layer undergoes endosomal disassembly essential for membrane fusion.

Ebola viruses (EBOVs) assemble into filamentous virions, whose shape and stability are determined by the matrix viral protein 40 (VP40). Virus entry into host cells occurs via membrane fusion in late endosomes; however, the mechanism of how the remarkably long virions undergo uncoating, including virion disassembly and nucleocapsid release into the cytosol, remains unknown. Here, we investigate the structural architecture of EBOVs entering host cells and discover that the VP40 matrix disassembles prior to membrane fusion. We reveal that VP40 disassembly is caused by the weakening of VP40-lipid…

Spatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories.

Ebola virus (EBOV) infection induces the formation of membrane-less, cytoplasmic compartments termed viral factories, in which multiple vira … g EBOV infection. Unlike droplet-like viral factories, network-like factories are inactive for EBOV nucleocapsid assembly. This unique view of EBOV propagation suggests a form-to-function relationship that describes how physical properties and internal structures of biomolecular condensates influence viral biogenesis.

Persistent SARS-CoV-2 antigen presence in multiple organs of a naturally infected cat from Brazil.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the disease coronavirus 2019 (COVID-19) … 43 days after the molecular diagnosis. Immunohistochemistry at post-mortem examination demonstrated nucleocapsid protein in samples from the lungs, kidneys, nasal conchae, trachea, intestine, brain and spleen. CONCLUSION: The present study has highlighted the possibility that viral antigens can be detected by immunohistochemistry in multiple organs six weeks …

Coronaviruses exploit a host cysteine-aspartic protease for replication.

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory … ost factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and imp …

COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses.

Cellular and humoral immunity to SARS-CoV-2 is critical to control primary infection and correlates with severity of disease. The role of SARS-CoV-2-specific T cell immunity, its relationship to antibodies, and pre-existing immunity against endemic coronaviruses (huCoV), which has been hypothesized to be protective, were investigated in 82 healthy donors (HDs), 204 recovered (RCs), and 92 active COVID-19 patients (ACs). ACs had high amounts of anti-SARS-CoV-2 nucleocapsid and spike IgG but lymphopenia and overall reduced antiviral T cell responses due to the inflammatory milieu, expression of …

Antibodies specific to SARS-CoV-2 proteins N, S and E in COVID-19 patients in the normal population and in historical samples.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally; recognition of immune responses to this virus will be crucial for coronavirus disease 2019 (COVID-19) control, prevention and treatment. We comprehensively analysed IgG and IgA antibody responses to the SARS-CoV-2 nucleocapsid protein (N), spike protein domain 1 (S1) and envelope protein (E) in: SARS-CoV-2-infected patient, healthy, historical and pre-epidemic samples, including patients' medical, epidemiological and diagnostic data, virus-neutralizing capability and kinetics. N-specific IgG and IgA are the most …

Immunological imprinting of the antibody response in COVID-19 patients.

In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for whi … coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

Current Status of Multiple Drug Molecules, and Vaccines: An Update in SARS-CoV-2 Therapeutics.

The coronavirus disease of 2019 (COVID-19) is a pandemic disease that has taken the lives of many around the world. It is caused by severe a … e of the SARS-CoV-2 virus comprises of S proteins, M proteins, E proteins, hemagglutinin esterases, nucleocapsid proteins, and a 30-kb RNA genome. Viral proteases cleave these polyproteins and RNA-dependent polymerases replicate the genome. Currently, there are no effective therapies against this new disease. Numerous investigators are developing novel proteas …

Coronavirus Disease (COVID-19): Current Status and Prospects for Drug and Vaccine Development.

The Coronavirus disease 2019 (COVID-19) pandemic has spread to almost all nooks and corners of the world. There are numerous potential approaches to pharmacologically fight COVID-19: small-molecule drugs, interferon therapies, vaccines, oligonucleotides, peptides, and monoclonal antibodies. Medications are being developed to target the spike, membrane, nucleocapsid or envelope proteins. The spike protein is also a critical target for vaccine development. Immunoinformatic approaches are being used for the identification of B cell and cytotoxic T lymphocyte (CTL) epitopes in the SARS-CoV-2 spike…

Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization.

Alphaviruses are enveloped pathogens that cause arthritis and encephalitis. Here, we report a 4.4-Å cryoelectron microscopy (cryo-EM) structure of eastern equine encephalitis virus (EEEV), an alphavirus that causes fatal encephalitis in humans. Our analysis provides insights into viral entry into host cells. The envelope protein E2 showed a binding site for the cellular attachment factor heparan sulfate. The presence of a cryptic E2 glycan suggests how EEEV escapes surveillance by lectin-expressing myeloid lineage cells, which are sentinels of the immune system. A mechanism for nucleocapsid co…

[Detection of the new influenza A subtype H1pdmN2 in a pig holding with severe respiratory symptoms].

Early in 2012 fattening pigs in a pig holding in northern Baden-Württemberg developed serious respiratory disease. After detecting Influenza … ever, using an ELISA, selected serum samples showed positive reactions against the highly conserved nucleocapsid protein. Performing an HI test using the isolated virus as antigen, significantly positive titers between 1:80 and 1:160 were obtained. The virus isolate was finally identified by molecular methods as a subtype H1pdmN2, a reassortant between the hum …

Development of a Newcastle disease virus vector expressing a foreign gene through an internal ribosomal entry site provides direct proof for a sequential transcription mechanism.

In the present study, we developed a novel approach for foreign gene expression by Newcastle disease virus (NDV) from a second ORF through an internal ribosomal entry site (IRES). Six NDV LaSota strain-based recombinant viruses vectoring the IRES and a red fluorescence protein (RFP) gene behind the nucleocapsid (NP), phosphoprotein (P), matrix (M), fusion (F), haemagglutinin-neuraminidase (HN) or large polymerase (L) gene ORF were generated using reverse genetics technology. The insertion of the second ORF slightly attenuated virus pathogenicity, but did not affect ability of the virus to grow…

Ядро антигенной ДНК и белковые вакцины от гепатита Вудчака вызывают качественно различные иммунные реакции, которые влияют на реакцию Т на отзыв клеток и антивирусные эффекты.

Считается, что иммунитет Т типа 1 (Th1) играет доминирующую роль в обезвреживании вирусов гепаднавирусной инфекции. Тем не менее, достандартная реакция типа Т2 позволила эффективно контролировать гепаднавирусную инфекцию в моделях животных. Мы изучили, как достандартная реакция TH1/2 контролирует гепаднавирусное воспроизведение с использованием недавно созданных моделей мыши. ДНК (PWHCIm, PCTLA-4-C) и белковые вакцины, основанные на нуклеокапсидском белоке (WHCCAg) вирусе гепатита вудчака (WHV), сформулировали конкретные иммунные реакции с различными характеристиками. Предстандартные ответы оп

Совпадение в аннотации оригинала
T helper type 1 (Th1) immunity was considered to play a dominant role in viral clearance of hepadnaviral infection. However, pre-primed Th2 … using the newly established mouse models. DNA (pWHcIm, pCTLA-4-C) and protein vaccines based on the nucleocapsid protein (WHcAg) of woodchuck hepatitis virus (WHV) primed specific immune responses with distinct features. The pre-primed responses determined the characteristics of recall responses if challenged with a WHcAg-expressing adenoviral vector. Vaccinat …