Sci Rep. 2018 Apr 13;8(1):5960. doi: 10.1038/s41598-018-24448-2.
APOBEC3-mediated restriction of RNA virus replication.
Milewska A1,2, Kindler E3,4, Vkovski P3,4,5, Zeglen S6,7, Ochman M8, Thiel V3,4, Rajfur Z9, Pyrc K10,11.
Abstract
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.
- PMID:
- 29654310
- PMCID:
- PMC5899082
- DOI:
- 10.1038/s41598-018-24448-2
- [Indexed for MEDLINE]
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