Topoisomerase 3b is dispensable for replication of a positive-sense RNA virus--murine coronavirus.
Antiviral Res
; 208: 105451, 2022 Dec.
Article
in English
| MEDLINE | ID: covidwho-2085917
ABSTRACT
A recent study demonstrated that a DNA-RNA dual-activity topoisomerase complex, TOP3B-TDRD3, is required for normal replication of positive-sense RNA viruses, including several human flaviviruses and coronaviruses; and the authors proposed that TOP3B is a target of antiviral drugs. Here we examined this hypothesis by investigating whether inactivation of Top3b can inhibit the replication of a mouse coronavirus, MHV, using cell lines and mice that are inactivated of Top3b or Tdrd3. We found that Top3b-KO or Tdrd3-KO cell lines generated by different CRISPR-CAS9 guide RNAs have variable effects on MHV replication. In addition, we did not find significant changes of MHV replication in brains or lungs in Top3B-KO mice. Moreover, immunostaining showed that Top3b proteins are not co-localized with MHV replication complexes but rather, localized in stress granules in the MHV-infected cells. Our results suggest that Top3b does not have a universal role in promoting replication of positive-sense RNA virus, and cautions should be taken when targeting it to develop anti-viral drugs.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA Viruses
/
Coronavirus Infections
/
Coronavirus
/
Murine hepatitis virus
Limits:
Animals
Language:
English
Journal:
Antiviral Res
Year:
2022
Document Type:
Article
Affiliation country:
J.antiviral.2022.105451
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