Study demonstrates how pan-sarbecovirus ORF7a protein plays a role in evading host immunity RockefellerUniv PNASNews SARSCoV2 COVID19 PanSarbecovirus ORF7a Protein Immunity
By Neha MathurSep 26 2022Reviewed by Aimee Molineux In a recent study published in Immunity, researchers demonstrated how sarbecovirus family down-regulates major histocompatibility complex-I surface expression to evade cellular immunity.
About the study In the present study, researchers used HIV-1 a based lentiviral vector to express all SARS-CoV-2 ORFs as annotated in a study by Wu et al. and Gordon et al. They transduced human 293T cells with these SARS-CoV-2 proteins after two days. Then, the team measured MHC-I surface levels by flow cytometry using a pan-human leukocyte antigen class I-reactive monoclonal antibody.
Study findings Expression of ORF7a reduced MHC-I levels on the cell surface by approximately fivefold, whereas expression of other individual viral proteins did not affect MHC-I surface levels. None of the SARS-CoV-2 viral ORFs reduced the levels of tetherin stably expressed on the surface of 293T cells, underscoring the specificity of the effect of ORF7a on MHC-I.Download a copy today
Western blot analysis revealed the mechanism by which ORF7a down-regulated MHC-I expression. When the researchers transduced cells expressing ORF7a with the ORF7a lentivirus at a sufficient multiplicity of infection , their total endogenous cellular MHC-I increased. It also showed slightly accelerated migration, thus indicating that ORF7a triggered the intracellular accumulation of MHC-I and altered its post-translational modification.
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