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Host genetic diversity and genetic variations of SARS-CoV-2 in COVID-19 pathogenesis and the effectiveness of vaccination.

ABSTRACT: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the outbreak of coronavirus disease 2019 (COVID-19), has shown a vast range of clinical manifestations from asymptomatic to life-threatening symptoms. To figure out the cause of this heterogeneity, studies demonstrated the trace of genetic diversities whether in the hosts or the virus itself. With this regard, this review provides a comprehensive overview of how host genetic such as those related to the entry of the virus, the immune-related genes, gender-related genes, disease-related genes, and also host epigenetic could influence the severity of COVID-19. Besides, the mutations in the genome of SARS-CoV-2 ^__leading to emerging of new variants^__ per se affect the affinity of the virus to the host cells and enhance the immune escape capacity. The current review discusses these variants and also the latest data about vaccination effectiveness facing the most important variants.

SUBMITTER: Delshad M

PROVIDER: S-EPMC9359488 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Host genetic diversity and genetic variations of SARS-CoV-2 in COVID-19 pathogenesis and the effectiveness of vaccination.

Delshad Mahda M Sanaei Mohammad-Javad MJ Pourbagheri-Sigaroodi Atieh A Bashash Davood D

International immunopharmacology 20220808

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the outbreak of coronavirus disease 2019 (COVID-19), has shown a vast range of clinical manifestations from asymptomatic to life-threatening symptoms. To figure out the cause of this heterogeneity, studies demonstrated the trace of genetic diversities whether in the hosts or the virus itself. With this regard, this review provides a comprehensive overview of how host genetic such as those related to the entry of th ...[more]

PMID: 35963158

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Project description:Zaire ebolavirus (ZEBOV) is among the deadliest known human pathogens, causing severe hemorrhagic fever with high case fatality rates ranging from 70-90%. The lack of effective vaccines or treatment available for ZEBOV renders this pathogen as a significant global biodefense threat, as evidenced by the current, highly lethal outbreak of a novel ZEBOV variant in western Africa. Existing mouse models of lethal ZEBOV infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever (EHF) including prolonged blood coagulation, acute hepatitis, disseminated intravascular coagulation (DIC), and death from hemorrhagic shock, thus restricting pathogenesis studies to non-human primates (NHP). This has prevented rapid evaluation of countermeasures in outbreak scenarios, and impeded a comprehensive understanding of how host responses to infection contribute to severe EHF disease. Here we demonstrate that mice from the Collaborative Cross (CC), a panel of reproducible, recombinant inbred animals that span the genetic breadth of three murine subspecies, are susceptible to a spectrum of disease phenotypes following ZEBOV infection. In contrast to C57Bl6/J mice, which develop lethal disease without symptoms of EHF, CC recombinant inbred intercrossed (CC-RIX) lines develop either complete resistance to lethal disease or severe EHF characterized by prolonged coagulation times and 100% mortality. Disease resistance and survival is not dependent on viral tropism, as both resistant and EHF-susceptible lines show similar inflammation and cytopathic effect in target organs. Transcriptomics reveal potential mechanisms for both induction of severe hemorrhage in EHF mediated by IL-6 and vascular activation, and resistance to lethal infection by induction of lymphocyte differentiation and cellular adhesion. These data demonstrate that host responses specific to unique genetic backgrounds determine susceptibility to hemorrhagic syndrome independent of virus replication. The CC represents a novel mouse model for studying EHF pathogenesis, and we anticipate that it will be applied immediately to developing and evaluating therapeutic countermeasures. Microarrays were performed on liver and spleen samples from mice collected at days 1, 3, and 5 post-infection with mouse adapted Zaire ebolavirus or from time-matched mock-infected animals.

Dataset Information

Host genetic diversity and genetic variations of SARS-CoV-2 in COVID-19 pathogenesis and the effectiveness of vaccination.

Publications

Host genetic diversity and genetic variations of SARS-CoV-2 in COVID-19 pathogenesis and the effectiveness of vaccination.

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