The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation

Journal of Molecular Biology, Journal Year: 2021, Volume and Issue: 434(6), P. 167280 - 167280

Published: Oct. 1, 2021

Language: Английский

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SARS-CoV-2 and the Host Cell: A Tale of Interactions

Frontiers in Virology, Journal Year: 2022, Volume and Issue: 1

Published: Jan. 12, 2022

The ability of a virus to spread between individuals, its replication capacity and the clinical course infection are macroscopic consequences multifaceted molecular interaction viral components with host cell. heavy impact COVID-19 on world population, economics sanitary systems calls for therapeutic prophylactic solutions that require deep characterization interactions occurring cells. Unveiling how SARS-CoV-2 engages factors throughout life cycle is therefore fundamental understand pathogenic mechanisms underlying design antiviral therapies strategies. Two years into pandemic, this review provides an overview interplay cell, focus machinery compartments pivotal cellular response. Starting cell surface, following replicative through entry pathways, survival in cytoplasm, egress from infected unravels complex network highlighting knowledge has potential set basis development innovative

Language: Английский

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Syncytia formation during SARS-CoV-2 lung infection: a disastrous unity to eliminate lymphocytes

Cell Death and Differentiation, Journal Year: 2021, Volume and Issue: 28(6), P. 2019 - 2021

Published: May 12, 2021

Language: Английский

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Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 3, 2021

The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that activates innate response through cytosolic DNA sensing cGAS-STING pathway. induces cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin shuttled from nucleus as result cell-to-cell fusion upon infection. We further demonstrate expression spike protein ACE2 cells sufficient trigger cytoplasmic cell fusion. Furthermore, chromatin-cGAS-STING pathway, but not MAVS-mediated viral contributes interferon pro-inflammatory gene Finally, show required for antiviral responses against SARS-CoV-2, STING-activating compound potently inhibits replication. Together, our study reported previously unappreciated mechanism which infection, mediated infected cells. Targeting pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend knowledge defense showing cells' self-nucleic acids can be employed "danger signal" alarm system.

Language: Английский

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Immune evasion of SARS-CoV-2 from interferon antiviral system

Computational and Structural Biotechnology Journal, Journal Year: 2021, Volume and Issue: 19, P. 4217 - 4225

Published: Jan. 1, 2021

The on-going pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has led to unprecedented medical and socioeconomic crises. Although the viral pathogenesis remains elusive, deficiency effective antiviral interferon (IFN) responses upon SARS-CoV-2 infection been recognized as a hallmark COVID-19 contributing pathology progress. Recently, multiple proteins encoded have shown act potential IFN antagonists with diverse possible mechanisms. Here, we summarize discuss strategies for evasion innate immunity (particularly responses), understanding which will facilitate not only elucidation but also development intervention therapies.

Language: Английский

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SARS-CoV-2: A Master of Immune Evasion

Biomedicines, Journal Year: 2022, Volume and Issue: 10(6), P. 1339 - 1339

Published: June 7, 2022

Viruses and their hosts have coevolved for a long time. This coevolution places both the pathogen human immune system under selective pressure; on one hand, has evolved to combat viruses virally infected cells, while developed sophisticated mechanisms escape recognition destruction by system. SARS-CoV-2, that is causing current COVID-19 pandemic, shown remarkable ability antibody neutralization, putting vaccine efficacy at risk. One of virus’s evasion strategies mitochondrial sabotage: reactive oxygen species (ROS) production, physiology impaired, interferon antiviral response suppressed. Seminal studies identified an intra-cytoplasmatic pathway viral infection, which occurs through construction tunneling nanotubes (TNTs), hence enhancing infection avoiding surveillance. Another method evading monitoring disruption antigen presentation. In this scenario, SARS-CoV-2 reduces MHC-I molecule expression: SARS-CoV-2’s open reading frames (ORF 6 ORF 8) produce proteins specifically downregulate molecules. All these are also exploited other elude detection should be studied in depth improve effectiveness future treatments. Compared Wuhan strain or Delta variant, Omicron mutations impaired its generate syncytia, thus reducing pathogenicity. Conversely, allowed it neutralization preventing cellular recognition, making most contagious evasive variant date.

Language: Английский

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Spike protein mediated membrane fusion during SARS‐CoV‐2 infection

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Oct. 13, 2022

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to public health and quickly become global concern. infection of SARS-CoV-2 begins with the binding its spike protein receptor-angiotensin-converting enzyme (ACE2), which, after series conformation changes, results in fusion viral-cell membranes release viral RNA genome into cytoplasm. In addition, infected host cells can express on their cell surface, which will interact ACE2 neighboring cells, leading membrane formation multinucleated or syncytia. Both entry syncytia are mediated spike-ACE2 interaction share some common mechanisms fusion. Here this review, we summarize our current understanding spike-mediated fusion, may shed light future broad-spectrum antiviral development.

Language: Английский

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HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread

Viruses, Journal Year: 2022, Volume and Issue: 14(1), P. 152 - 152

Published: Jan. 14, 2022

So far, only two retroviruses, human immunodeficiency virus (HIV) (type 1 and 2) T-cell lymphotropic type (HTLV-1), have been recognized as pathogenic for humans. Both viruses mainly infect CD4+ T lymphocytes. HIV replication induces the apoptosis of CD4 lymphocytes, leading to development acquired syndrome (AIDS). After a long clinical latency period, HTLV-1 can transform with subsequent uncontrolled proliferation manifestation disease called adult leukemia (ATLL). Certain infected patients develop neurological autoimmune disorder HTLV-1-associated myelopathy, also known tropical spastic paraparesis (HAM/TSP). are transmitted between individuals via blood transfusion, tissue/organ transplantation, breastfeeding, sexual intercourse. Within host, these spread utilizing either cell-free or cell-to-cell modes transmission. In this review, we discuss mechanisms importance each mode transmission biology HIV-1 HTLV-1.

Language: Английский

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HIV–Host Cell Interactions

Cells, Journal Year: 2023, Volume and Issue: 12(10), P. 1351 - 1351

Published: May 9, 2023

The development of antiretroviral drugs (ARVs) was a great milestone in the management HIV infection. ARVs suppress viral activity host cell, thus minimizing injury to cells and prolonging life. However, an effective treatment has remained elusive for four decades due successful immune evasion mechanisms virus. A thorough understanding molecular interaction with cell is essential both preventive curative therapies This review highlights several inherent that promote its survival propagation, such as targeting CD4+ lymphocytes, downregulation MHC class I II, antigenic variation envelope complex minimizes antibody access, how they collaboratively render system unable mount response.

Language: Английский

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Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 288 - 288

Published: Feb. 13, 2024

Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target HIV-1, their specific roles pathophysiology infection initially largely neglected. However, numerous studies performed over past decade, both vitro cell culture systems vivo monkey humanized mouse animal models, led growing evidence that play important direct indirect HIV-1 pathogenesis. It has been recently proposed are likely involved all stages pathogenesis, virus transmission dissemination, but above all, viral persistence through establishment, together with latently infected reservoirs many host tissues, major obstacle eradication people living HIV. Infected indeed found, very often multinucleated giant expressing antigens, almost lymphoid non-lymphoid tissues HIV-1-infected patients, where they can probably persist for long period time. In addition, also participate, directly targets or indirectly key regulators innate immunity inflammation, chronic inflammation associated clinical disorders observed HIV, even patients receiving effective antiretroviral therapy. The main objective this review is therefore summarize recent findings, revisit older data, regarding critical functions infection, found well during different

Language: Английский

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