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2018 ; 8
(1
): 5960
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APOBEC3-mediated restriction of RNA virus replication
#MMPMID29654310
Milewska A
; Kindler E
; Vkovski P
; Zeglen S
; Ochman M
; Thiel V
; Rajfur Z
; Pyrc K
Sci Rep
2018[Apr]; 8
(1
): 5960
PMID29654310
show ga
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.
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