TY  - JOUR
AU  - Nchioua, Rayhane
AU  - Kmiec, Dorota
AU  - Krchlikova, Veronika
AU  - Mattes, Sarah
AU  - Noettger, Sabrina
AU  - Bibollet-Ruche, Frederic
AU  - Russell, Ronnie M
AU  - Sparrer, Konstantin M J
AU  - Charpentier, Thomas
AU  - Tardy, Frédéric
AU  - Bosinger, Steven E
AU  - Sauter, Daniel
AU  - Hahn, Beatrice H
AU  - Kirchhoff, Frank
TI  - Host ZAP activity correlates with the levels of CpG suppression in primate lentiviruses.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 122
IS  - 15
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DZNE-2025-00502
SP  - e2419489122
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Humans
KW  - Dinucleoside Phosphates: metabolism
KW  - Dinucleoside Phosphates: genetics
KW  - Lentiviruses, Primate: genetics
KW  - Lentiviruses, Primate: metabolism
KW  - RNA-Binding Proteins: metabolism
KW  - RNA-Binding Proteins: genetics
KW  - Simian Immunodeficiency Virus: genetics
KW  - CpG Islands: genetics
KW  - HIV-1: genetics
KW  - CpG suppression (Other)
KW  - primate lentiviruses (Other)
KW  - virus-host arms race (Other)
KW  - zinc-finger antiviral protein (Other)
KW  - Dinucleoside Phosphates (NLM Chemicals)
KW  - RNA-Binding Proteins (NLM Chemicals)
KW  - cytidylyl-3'-5'-guanosine (NLM Chemicals)
KW  - ZC3HAV1 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40178887
DO  - DOI:10.1073/pnas.2419489122
UR  - https://pub.dzne.de/record/277882
ER  -