Journal Article

DZNE-2025-00502

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Host ZAP activity correlates with the levels of CpG suppression in primate lentiviruses.

Nchioua, R. ; Kmiec, D. ; Krchlikova, V. ; Mattes, S. ; Noettger, S. ; Bibollet-Ruche, F. ; Russell, R. M. ; Sparrer, K. M. J.DZNE* ; Charpentier, T. ; Tardy, F. ; Bosinger, S. E. ; Sauter, D. ; Hahn, B. H. ; Kirchhoff, F.

2025
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.2419489122

Abstract: 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.

Keyword(s): Animals (MeSH) ; Humans (MeSH) ; Dinucleoside Phosphates: metabolism (MeSH) ; Dinucleoside Phosphates: genetics (MeSH) ; Lentiviruses, Primate: genetics (MeSH) ; Lentiviruses, Primate: metabolism (MeSH) ; RNA-Binding Proteins: metabolism (MeSH) ; RNA-Binding Proteins: genetics (MeSH) ; Simian Immunodeficiency Virus: genetics (MeSH) ; CpG Islands: genetics (MeSH) ; HIV-1: genetics (MeSH) ; CpG suppression ; primate lentiviruses ; virus-host arms race ; zinc-finger antiviral protein ; Dinucleoside Phosphates ; RNA-Binding Proteins ; cytidylyl-3'-5'-guanosine ; ZC3HAV1 protein, human

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Contributing Institute(s):

1. Neurovirology and Neuroinflammation (AG Sparrer)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2025

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