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The ability of zinc finger antiviral protein (ZAP) to recognize and respond to RNA virus sequences with elevated frequencies of CpG dinucleotides has been proposed as a functional part of the vertebrate innate immune antiviral response. It has been further proposed that ZAP activity shapes compositions of cytoplasmic mRNA sequences to avoid self-recognition, particularly mRNAs for interferons (IFNs) and IFN-stimulated genes (ISGs) expressed during the antiviral state. We investigated whether restriction of the replication of mutants of influenza A virus (IAV) and the echovirus 7 (E7) replicon with high CpG and UpA frequencies varied in different species of mammals and birds. Cell lines from different bird orders showed substantial variability in restriction of CpG-high mutants of IAV and E7 replicons, whereas none restricted UpA-high mutants, in marked contrast to universal restriction of both mutants in mammalian cells. Dinucleotide representation in ISGs and IFN genes was compared with those of cellular transcriptomes to determine whether potential differences in inferred ZAP activity between species shaped dinucleotide compositions of highly expressed genes during the antiviral state. While mammalian type 1 IFN genes typically showed often profound suppression of CpG and UpA frequencies, there was no oversuppression of either in ISGs in any species, irrespective of their ability to restrict CpG- or UpA-high mutants. Similarly, genome sequences of mammalian and avian RNA viruses were compositionally equivalent, as were IAV strains recovered from ducks, chickens and humans. Overall, we found no evidence for host variability in inferred ZAP function shaping host or viral transcriptome compositions.

Original publication

DOI

10.1261/rna.079102.122

Type

Journal article

Journal

RNA (New York, N.Y.)

Publication Date

08/2022

Volume

28

Pages

1089 - 1109

Addresses

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kingdom.

Keywords

Animals, Chickens, Mammals, Humans, Influenza A virus, RNA, Messenger, RNA, Viral, Antiviral Agents, Virus Replication, Transcriptome