Host ZAP activity correlates with the levels of CpG suppression in primate lentiviruses
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Rayhane Nchioua
Institute of Molecular Virology, Ulm University Medical Center
Dorota Kmiec
Institute of Molecular Virology, Ulm University Medical Center
Veronika Krchlikova
Research group "Mechanisms of innate Antiviral immunity", Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen
Sarah Mattes
Institute of Molecular Virology, Ulm University Medical Center
Sabrina Noettger
Institute of Molecular Virology, Ulm University Medical Center
Frederic Bibollet-Ruche
Ronnie M. Russell
Department of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania
Konstantin M. J. Sparrer
Institute of Molecular Virology
Thomas Charpentier
Zoo La Palmyre
Frédéric Tardy
Zoo Sanary-sur-Mer
Steven E. Bosinger
Department of Pathology & Laboratory Medicine, Emory University, Division of Microbiology and Immunology, Emory National Primate Research Center
Daniel Sauter
Research group "Mechanisms of innate Antiviral immunity", Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen
Beatrice H. Hahn
Frank Kirchhoff
Institute of Molecular Virology, Ulm University Medical Center