Research suggests that ORF6 is a major SARS-CoV-2 innate immune antagonist Research SARSCoV2 Coronavirus Disease COVID ORF6 biorxivpreprint IcahnMountSinai txbiomed UCSF
Study: Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis. Image Credit: ktsdesign / Shutterstock
About the study In the present study, researchers used biochemical and molecular methods, combined with in vivo animal studies, to dissect the impact of the innate immune antagonist ORF6 on the host response to SARS-CoV-2 infection. In addition, they functionally characterized the ORF6 D61L mutation common between Omicron BA.2 and BA.4 sub-variants.
For in vivo studies, the team infected eight-week-old female hamsters with 5x105 plaque-forming units of either the parental rSARS-CoV-2 WT or the ORF6-deficient virus. They recorded weight loss in all animals from the day of infection to 15 days post-infection . Then, they sacrificed these animals at 2, 4, and 6 dpi to harvest their lungs and nasal turbinates to determine viral titer and histopathological evaluations.
Regarding in vivo effects of ORF6, the authors noted that hamsters infected with an ORF6 deleted SARS-CoV-2 pseudoviruses suffered minimal weight loss and reduced lung injury and type 2 alveolar cells' hyperplasia. These findings pointed to an increased STAT1 translocation and interferon-stimulating genes expression in the lungs.
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