Host ZAP activity correlates with the levels of CpG suppression in primate lentiviruses

• 成果类型: Article
• 署名作者: Nchioua, Rayhane; Kmiec, Dorota; Krchlikova, Veronika; Mattes, Sarah; Noettger, Sabrina; Bibollet-Ruche, Frederic; Russell, Ronnie M.; Sparrer, Konstantin M. J.; Charpentier, Thomas; Tardy, Frederic; Bosinger, Steven E.; Sauter, Daniel; Hahn, Beatrice H.; Kirchhoff, Frank
• 署名单位: Ulm University; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; University of Pennsylvania; Helmholtz Association; German Center for Neurodegenerative Diseases (DZNE); Emory University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9444
• DOI: 10.1073/pnas.2419489122
• 发表日期: 2025-04-15
• 关键词: dna methylation; non-self; viruses; origin; genome; siv; replication; inhibition; expression; sequence

摘要

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 Cercopithecus 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.