Viruses have evolved ways of degrading host mRNAs to favor their survival and maximize expression of their own mRNAs. Inducing cellular mRNAs degradation eventually leads to shutoff of host proteins expression and gives viruses transcripts a competitive edge for access to the cellular translation machinery and counteract the antiviral response.
Most viruses proceed by expressing an endonuclease that cleaves host mRNAs, which are in turn degraded by an host exonuclease, like Xrn1 in mammals .
During the lytic replication cycle of Kaposi’s sarcoma-associated herpesvirus (KSHV), SOX protein promotes massive cellular mRNAs decay through an endonucleotic internal cleavage of host mRNAs. The resulting RNA fragments are eliminated by the cellular RNA degradation machinery. During the lytic replication cycle of Human herpesvirus 1 (HSV-1), VHS protein triggers accelerated degradation of host mRNAs and also seems to relocalize PABP. VHS would specifically target actively translated mRNAs through interactions with host EIF4F components (e.g. EIF4H, EIF4B, EIF4A2 ) and degrade them by endonucleotic RNA cleavage.
SARS NSP1 binds to 40s ribosomes and induces endonucleotic RNA cleavage of host mRNAs leading to their degradation. The presence of a 5'-end leader sequence protects SARS mRNAs from NSP1 cleavage.
Influenza A virus PA-X protein encoded on segment 3 by ribosomal frameshifting may have a messenger RNA endonuclease activity and play a role in the observed reduced cellular protein synthesis.
Viruses inducing host mRNA decay:
|(Sub)Family||Virus||Viral protein||mRNA decay strategy||references|
|Coronaviridae||SARS-CoV,bat-Cov ( Betacoronavirus )||NSP1||Endonucleotic mRNAs cleavage||Gammaherpesvirinae||HHV-8/KSHV||Shutoff alkaline exonuclease||Endonucleotic mRNAs cleavage|
|MHV68||Shutoff alkaline exonuclease||Endonucleotic mRNAs cleavage|
|EBV||Shutoff alkaline exonuclease||?|
|Orthomyxoviridae||Influenza A virus||PA-X protein||Endonucleotic mRNAs cleavage|
|Alphaherpesvirinae||HHV-1||VHS protein||Endonucleotic mRNAs cleavage|