Impacts of the SARS-CoV-2 Spike Protein on the Innate Immune System: A Review

Cureus, Год журнала: 2024, Номер unknown

Опубликована: Март 26, 2024

The Spike protein enables the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to multiple receptors, including angiotensin-converting enzyme (ACE2). Scientific studies also indicate that is involved in forms of disease 2019 (COVID-19), "long-haul COVID diseases" - known as "long syndromes" or "post-acute sequelae SARS-CoV-2 infection" (PACS) or, recently, adverse reactions lipid nanoparticle-messenger ribonucleic acid (mRNA) vaccines other anti-COVID19 products. Numerous mutations, notably within subunit 1 (S1), prevent neutralization antibodies, but more generally, virus has developed numerous strategies avoid immune system surveillance, especially type-I interferons (IFN-I). Meanwhile, a "hyperinflammatory" state, named "cytokine storm," sets in. However, what role does play escape mechanisms? Can its inflammatory activities affect IFN-I? Does block IFN-I hijack them for benefits? What are potential consequences? This article was written provide an up-to-date and general overview impact on innate effectors at molecular level.

Язык: Английский

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Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Апрель 24, 2024

Variants of SARS-CoV-2, defined mainly by mutations in the spike glycoprotein, have emerged throughout COVID-19 pandemic and will undoubtedly continue to emerge future. Spike strongly influences virus phenotype, it is therefore critical understand evolution this viral protein during distinct phases pandemic. Here, we generated a panel recombinant viruses carrying from 27 most significant variants, circulating between 2020 2024, within an otherwise identical genomic backbone. We systematically assessed phenotypic traits these both vitro vivo hamsters. Overall, determined trajectories among variants before (“pre-Omicron") after (“post-Omicron”) emergence Omicron. Spillover SARS-CoV-2 human population was followed period adaptation fine-tuning host pre-Omicron variants. Omicron simultaneously “reset” several established phenotypes previously Since then, post-Omicron maintained its enhanced tropism for nasal epithelium but displayed over time typical These data suggest that may be possible with features pre-

Язык: Английский

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Host Cell Proteases Involved in Human Respiratory Viral Infections and Their Inhibitors: A Review

Опубликована: Май 15, 2024

Viral tropism is most commonly linked to receptor use, but host cell protease use can be a notable factor in susceptibility infection. Here we review the of proteases by human viruses, focusing on those with primarily respiratory tropism, particularly SARS-CoV-2. We first describe various classes present tract, as well elsewhere body, and incorporate targeting these therapeutic drugs for humans. Host are also systemic spread viruses play important roles outside tract; therefore, address how affect across spectrum infections that occur humans, intending understand extrapulmonary

Язык: Английский

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The host protease KLK5 primes and activates spike proteins to promote human betacoronavirus replication and lung inflammation

Science Signaling, Год журнала: 2024, Номер 17(850)

Опубликована: Авг. 20, 2024

Coronaviruses rely on host proteases to activate the viral spike protein, which facilitates fusion with cell membrane and release of genomic RNAs into cytoplasm. The distribution specific in determines host, tissue, cellular tropism these viruses. Here, we identified kallikrein (KLK) family member KLK5 as a major protease secreted by human airway cells exploited multiple betacoronaviruses. cleaved both priming (S1/S2) activation (S2') sites proteins from various betacoronaviruses vitro. In contrast, KLK12 KLK13 displayed preferences for either S2' or S1/S2 site, respectively. Whereas worked concert SARS-CoV-2 MERS-CoV proteins, itself efficiently activated several betacoronaviruses, including SARS-CoV-2. Infection differentiated bronchial epithelial (HBECs) induced an increase that promoted virus replication. Furthermore, ursolic acid other related plant-derived triterpenoids inhibit effectively suppressed replication SARS-CoV, MERS-CoV, HBECs mitigated lung inflammation mice infected We propose is pancoronavirus factor promising therapeutic target current future coronavirus-induced diseases.

Язык: Английский

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Dynamin independent endocytosis is an alternative cell entry mechanism for multiple animal viruses

PLoS Pathogens, Год журнала: 2024, Номер 20(11), С. e1012690 - e1012690

Опубликована: Ноя. 14, 2024

Mammalian receptor-mediated endocytosis (RME) often involves at least one of three isoforms the large GTPase dynamin (Dyn). Dyn pinches-off vesicles plasma membrane and mediates uptake many viruses, although some viruses directly penetrate membrane. RME is classically interrogated by genetic pharmacological interference, but this has been hampered undesired effects. Here we studied virus entry in conditional knock-out (KO) mouse embryonic fibroblasts lacking expression all (Dyn-KO-MEFs). The small canine parvovirus known to use a single receptor, transferrin strictly depended on dynamin. Larger or multiple receptors, including alphaviruses, influenza, vesicular stomatitis, bunya, adeno, vaccinia, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rhinoviruses infected Dyn-KO-MEFs, albeit higher dosage than wild-type MEFs. In absence transmembrane protease serine subtype (TMPRSS2), which normally activates SARS-CoV-2 spike protein for fusion, angiotensin-converting enzyme (ACE2)-expressing MEFs predominantly through dynamin- actin-dependent endocytosis. presence TMPRSS2 ancestral Wuhan-strain bypassed both dynamin-dependent -independent endocytosis, was less sensitive endosome maturation inhibitors Omicron B1 XBB variants, supporting notion that variants do not efficiently TMPRSS2. Collectively, our study suggests function endocytic pits can be essential infection with single-receptor while it increases efficiency multi-receptor otherwise rely functional actin network infection.

Язык: Английский

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