Evolutionary effects of the AID/APOBEC family of mutagenic enzymes on human gamma-herpesviruses

Virus Evolution
Teresa MartinezThomas Maccarthy

Abstract

The human gamma-herpesviruses, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, establish lifelong latency in B cells and are associated with multiple malignancies. Virus-host coevolution often drive changes in both host immunity and in the viral genome. We consider one host immune mechanism, the activation-induced deaminase (AID)/APOBEC family of cytidine deaminases, that induces mutations in viral DNA. AID, the ancestral gene in the family has a conserved role in somatic hypermutation, a key step in antibody affinity maturation. The APOBEC3 subfamily, of which there are seven genes in human, have evolved antiviral functions and have diversified in terms of their expression pattern, subcellular localization, and DNA mutation motifs (hotspots). In this study, we investigated how the human gamma-herpesviruses have evolved to avoid the action of the AID/APOBEC enzymes and determine if these enzymes are contributing to the ongoing evolution of the viruses. We used computational methods to evaluate observed versus expected frequency of AID/APOBEC hotspots in viral genomes and found that the viruses have evolved to limit the representation of AID and certain APOBEC3 motifs. At the same time, the remaining hotspots wer...Continue Reading

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Citations

Aug 17, 2020·PLoS Pathogens·Florian PoulainNicolas A Gillet
Dec 23, 2020·PloS One·Yulong WeiXuhua Xia
Mar 13, 2021·Nature Communications·Adam LangenbucherMichael S Lawrence
Mar 7, 2021·Viruses·Adam Z ChengReuben S Harris
Aug 7, 2021·Trends in Genetics : TIG·Karla Cervantes-GraciaRichard Chahwan
Aug 11, 2021·Viruses·Shiva SadeghpourDiako Ebrahimi
May 5, 2021·Genome Biology and Evolution·Martijn CallensStéphanie Bedhomme

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Methods Mentioned

BETA
deamination
gene knockouts
for

Software Mentioned

CDUR
hyperfreq
ClustalW
TranslatorX
Biopython

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