Host ZAP activity correlates with the levels of CpG suppression in primate lentiviruses
Zinc-finger antiviral protein (ZAP) is thought to drive the suppression of CpG dinucleotides in many viruses to mimic the composition of their host genomes. However, in vivo evidence is sparse. Here, we investigated the reasons for unusually high CpG levels in SIVmus and SIVmon from mustached and mona monkeys, descendants of one of the precursors of HIV-1. We show that SIVmus is not resistant to ZAP inhibition. Instead, these <i>Cercopithecus</i> monkey hosts differ from other primate species by a splice site mutation and express the poorly active extralarge XL rather than the highly active L isoform of ZAP. Similarly, higher CpG levels in endogenous prosimian lentiviruses were associated with low activity of the corresponding host lemur ZAPs. In addition, lemur genes also show lower CpG suppression than other primates. Thus, the antiviral activity of ZAP not only affects suppression of CpG dinucleotides in viral transcripts but possibly also host genomes.
Authors
- Rayhane Nchioua (ORCID: https://orcid.org/0009-0001-1436-1232)
- Dorota Kmieć (ORCID: https://orcid.org/0000-0001-7302-6015)
- Daniel Sauter (ORCID: https://orcid.org/0000-0001-7665-0040)
- Beatrice H. Hahn (ORCID: https://orcid.org/0000-0002-9400-9887)
- Sabrina Noettger (ORCID: https://orcid.org/0000-0003-0059-5289)
- Steven E. Bosinger (ORCID: https://orcid.org/0000-0002-2116-5061)
- Konstantin M. J. Sparrer (ORCID: https://orcid.org/0000-0002-8682-1779)
- Ronnie M. Russell (ORCID: https://orcid.org/0000-0003-1484-4207)
- Veronika Krchlíková (ORCID: https://orcid.org/0000-0001-9192-5866)
- Frank Kirchhoff (ORCID: https://orcid.org/0000-0002-7052-2360)
- Thomas H. Charpentier (ORCID: https://orcid.org/0000-0002-7487-6051)
- Florence Tardy (ORCID: https://orcid.org/0000-0003-3968-4801)
- Frédéric Bibollet‐Ruche (ORCID: https://orcid.org/0009-0003-7518-6487)
- Sarah Mattes
Institutions
- Emory University (US)
- German Center for Neurodegenerative Diseases (DE)
- Zoo Miami (US)
- University Medical Center (US)
- Institute of Virology of the Slovak Academy of Sciences (SK)
- University of Pennsylvania (US)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-04-03
- DOI
- https://doi.org/10.1073/pnas.2419489122
- Citations
- 6
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 6.22
Funders
- Foundation for the National Institutes of Health
- Emory University
- European Commission
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Universität Ulm
- National Institutes of Health
- European Research Council