Key result
Sequence comparisons reveal SARS-CoV-2 Orf8 and Orf7a share an immunoglobulin-like origin despite rampant Orf8 evolution.
Why the study?
Orf8 is one of the most puzzling genes in the SARS lineage of coronaviruses, including SARS-CoV-2.
Orf8 originates from Orf7a and shares its immunoglobulin-like fold, suggesting potential immune evasion strategies by SARS-CoV-2.
Rapid Orf8 evolution supports SARS-CoV-2 variant surveillance; leaves open immunomodulatory roles pending functional validation.
Orf8 is one of the most puzzling genes in the SARS lineage of coronaviruses, including SARS-CoV-2. Using sophisticated sequence comparisons, we confirm its origins from Orf7a, another gene in the lineage that appears as more conserved, compared to Orf8. Orf7a is a potential immune antagonist of known structure, while a deletion of Orf8 was shown to decrease the severity of the infection in a cohort study. The subtle sequence similarities imply that Orf8 has the same immunoglobulin-like fold as Orf7a, confirmed by structure determination. We characterize the subgroups of this superfamily and demonstrate the highly idiosyncratic divergence patterns during the evolution of the virus.
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Neches et al. (2021) studied SARS-CoV-2. Sequence analysis of Orf8 and Orf7a was evaluated. Sequence comparisons reveal distant similarities between SARS-CoV-2 Orf8 and Orf7a, indicating a common origin with an immunoglobulin-like fold, where Orf8 is subject to rampant evolutionary change.
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