Blood group A epitopes do not facilitate entry of SARS-CoV-2.
Ontology highlight
ABSTRACT:
SUBMITTER: Schetelig J
PROVIDER: S-EPMC8014025 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:SARS-CoV-2 is a newly emerged coronavirus that caused the global COVID-19 outbreak in early 2020. COVID-19 is primarily associated with lung injury, but many other clinical symptoms such as loss of smell and taste demonstrated broad tissue tropism of the virus. Early SARS-CoV-2-host cell interactions and entry mechanisms remain poorly understood. Investigating SARS-CoV-2 infection in tissue culture, we found that the protease TMPRSS2 determines the entry pathway used by the virus. In the presence of TMPRSS2, the proteolytic process of SARS-CoV-2 was completed at the plasma membrane, and the virus rapidly entered the cells within 10 min in a pH-independent manner. When target cells lacked TMPRSS2 expression, the virus was endocytosed and sorted into endolysosomes, from which SARS-CoV-2 entered the cytosol via acid-activated cathepsin L protease 40-60 min post infection. Overexpression of TMPRSS2 in non-TMPRSS2 expressing cells abolished the dependence of infection on the cathepsin L pathway and restored sensitivity to the TMPRSS2 inhibitors. Together, our results indicate that SARS-CoV-2 infects cells through distinct, mutually exclusive entry routes and highlight the importance of TMPRSS2 for SARS-CoV-2 sorting into either pathway.
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Project description:Identification of risk factors for contracting and developing serious illness following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of paramount interest. Here, we performed a retrospective cohort analysis of all Danish individuals tested for SARS-CoV-2 between 27 February 2020 and 30 July 2020, with a known ABO and RhD blood group, to determine the influence of common blood groups on virus susceptibility. Distribution of blood groups was compared with data from nontested individuals. Participants (29% of whom were male) included 473 654 individuals tested for SARS-CoV-2 using real-time polymerase chain reaction (7422 positive and 466 232 negative) and 2 204 742 nontested individuals, accounting for ∼38% of the total Danish population. Hospitalization and death from COVID-19, age, cardiovascular comorbidities, and job status were also collected for confirmed infected cases. ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval [CI], 37.30-39.50) of the patients belonging to blood group O compared with 41.70% (95% CI, 41.60-41.80) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19. This study identifies ABO blood group as a risk factor for SARS-CoV-2 infection but not for hospitalization or death from COVID-19.
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Project description:A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Here we investigated receptor binding and protease activation of SARS-CoV-2 spike using biochemical and pseudovirus entry assays. Our findings have identified key cell entry mechanisms of SARS-CoV-2. First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. Third, unlike SARS-CoV, cell entry of SARS-CoV-2 is preactivated by proprotein convertase furin, reducing its dependence on target cell proteases for entry. The high hACE2 binding affinity of the RBD, furin preactivation of the spike, and hidden RBD in the spike potentially allow SARS-CoV-2 to maintain efficient cell entry while evading immune surveillance. These features may contribute to the wide spread of the virus. Successful intervention strategies must target both the potency of SARS-CoV-2 and its evasiveness.
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Project description:CD8 T cells from human donors were sorted with peptide-MHC multimers based on SARS-Cov-2 epitopes. For each donor the alpha and beta chains were sequenced separately
2022-04-25 | GSE201212 | GEO
Project description:Background and objectivesABO blood group may affect risk of SARS-CoV-2 infection and/or severity of COVID-19. We sought to determine whether IgG, IgA and neutralizing antibody (nAb) to SARS-CoV-2 vary by ABO blood group.Materials and methodsAmong eligible convalescent plasma donors, ABO blood group was determined via agglutination of reagent A1 and B cells, IgA and IgG were quantified using the Euroimmun anti-SARS-CoV-2 ELISA, and nAb titres were quantified using a microneutralization assay. Differences in titre distribution were examined by ABO blood group using non-parametric Kruskal-Wallis tests. Adjusted prevalence ratios (aPR) of high nAb titre (≥1:160) were estimated by blood group using multivariable modified Poisson regression models that adjusted for age, sex, hospitalization status and time since SARS-CoV-2 diagnosis.ResultsOf the 202 potential donors, 65 (32%) were blood group A, 39 (19%) were group B, 13 (6%) were group AB, and 85 (42%) were group O. Distribution of nAb titres significantly differed by ABO blood group, whereas there were no significant differences in anti-spike IgA or anti-spike IgG titres by ABO blood group. There were significantly more individuals with high nAb titre (≥1:160) among those with blood group B, compared with group O (aPR = 1·9 [95%CI = 1·1-3·3], P = 0·029). Fewer individuals had a high nAb titre among those with blood group A, compared with group B (aPR = 0·6 [95%CI = 0·4-1·0], P = 0·053).ConclusionEligible CCP donors with blood group B may have relatively higher neutralizing antibody titres. Additional studies evaluating ABO blood groups and antibody titres that incorporate COVID-19 severity are needed.
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