Expression of human APOBEC3 proteins A3C, A3F, and A3H inhibited HCoV-NL63 infection in vitro, resulting in a 1.5 to 2 log reduction in virus yield compared to control cells.
This study demonstrates that human APOBEC3 proteins can restrict coronavirus replication in vitro through mechanisms partially dependent on enzyme activity and nucleoprotein binding.
Effect estimate: 1.5-2 log reduction
p-value: p=<0.05
APOBEC3 family members are cytidine deaminases with roles in intrinsic responses to infection by retroviruses and retrotransposons, and in the control of other DNA viruses, such as herpesviruses, parvoviruses and hepatitis B virus. Although effects of APOBEC3 members on viral DNA have been demonstrated, it is not known whether they edit RNA genomes through cytidine deamination. Here, we investigated APOBEC3-mediated restriction of Coronaviridae. In experiments in vitro, three human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and limited production of progeny virus, but did not cause hypermutation of the coronaviral genome. APOBEC3-mediated restriction was partially dependent on enzyme activity, and was reduced by the use of enzymatically inactive APOBEC3. Moreover, APOBEC3 proteins bound to the coronaviral nucleoprotein, and this interaction also affected viral replication. Although the precise molecular mechanism of deaminase-dependent inhibition of coronavirus replication remains elusive, our results further our understanding of APOBEC-mediated restriction of RNA virus infections.
Milewska et al. (Wed,) conducted a other in HCoV-NL63 infection. APOBEC3 proteins (A3C, A3F, A3H) vs. GFP or untransfected cells was evaluated on HCoV-NL63 virus yield (1.5-2 log reduction, p=<0.05). Expression of human APOBEC3 proteins A3C, A3F, and A3H inhibited HCoV-NL63 infection in vitro, resulting in a 1.5 to 2 log reduction in virus yield compared to control cells.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: