CpG Frequency in the 5′ Third of the env Gene Determines Sensitivity of Primary HIV-1 Strains to the Zinc-Finger Antiviral Protein
Year: 2020
Type: article
Abstract: Evasion of the zinc-finger antiviral protein (ZAP) may drive CpG dinucleotide suppression in HIV-1 and many other viral pathogens but the viral determinants of ZAP sensitivity are poorly defined. Here, we examined CpG suppression and ZAP sensitivity in a large number of primate lentiviruses and demonstrate that their genomic frequency of CpGs varies substantially and does not correlate with ZAP sensitivity. We further show that the number of CpG residues in a defined region at the 5′ end of the env gene together with structural features plays a key role in HIV-1 susceptibility to ZAP and correlates with differences in clinical progression rates in HIV-1-infected individuals. Our identification of a specific part of env as a major determinant of HIV-1 susceptibility to ZAP restriction provides a basis for future studies of the underlying inhibitory mechanisms and their potential relevance in the pathogenesis of AIDS.
Source: mBio
Institutions: University Hospital Ulm, University of Pennsylvania
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,900
Awards: G1195029094, Restriction of HIV-1 transmission by type 1 interferons, BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy, G3504457557, Great Ape Reservoirs of Human Malaria, Exploiting the antigenic conservation of the Env trimer apex across primate lentiviral lineages for AIDS vaccine design, SHIV Env-antibody coevolution as a molecular guide to HIV-1 V3 glycan targeted vaccine design, Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens
OpenAlex ID: W3000475974