Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa

Retrovirology

Tarylee Reddy¹  Marcel Tongo²  Phyllis Kanki³  Beth Chaplin³  Jaclyn K. Mann⁴  Omotayo Farinre⁴  Kamini Gounder⁵  Thumbi Ndung’u⁶  Jill Gilmour⁷  Jonathan Hare⁷ 

[1] Biostatistics Research Unit, South African Medical Research Council, Durban, South Africa;Centre of Research for Emerging and Re-Emerging Diseases (CREMER), Yaoundé, Cameroon;Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA;HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa;HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa;Africa Health Research Institute, 4001, Durban, South Africa;HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa;Africa Health Research Institute, 4001, Durban, South Africa;Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA;Max Planck Institute for Infection Biology, Berlin, Germany;Division of Infection and Immunity, University College London, London, UK;International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory (HIL), Imperial College, London, UK;IAVI Global Headquarters, 125 Broad Street, 9th Floor,, New York, NY, USA;

关键词: HIV-1 subtype;    HIV-1 recombinants;    Sub-Saharan Africa;    HIV-1 replication capacity;    HLA class I alleles;   

DOI  :  10.1186/s12977-021-00554-4

来源: Springer

【 摘 要 】

BackgroundThe HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. Here, we tested the hypothesis that the subtypes prevalent in the East Africa, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower.ResultsGag-protease sequencing was performed on 213 and 160 antiretroviral-naïve chronically infected participants from West and East Africa respectively and bioinformatic tools were used to infer subtypes and recombination patterns. VRC of patient-derived gag-protease chimeric viruses from West (n = 178) and East (n = 114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in VRC and amino acid variants impacting VRC were identified by statistical methods. CRF02_AG (65%, n = 139), other recombinants (14%, n = 30) and pure subtypes (21%, n = 44) were identified in West Africa. Subtypes A1 (64%, n = 103), D (22%, n = 35), or recombinants (14%, n = 22) were identified in East Africa. Viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact VRC. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02_AG. HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with lower VRC in subtype A infected individuals from East Africa.ConclusionsAlthough prevalent viruses from West Africa displayed higher VRC than those from East Africa consistent with the hypothesis that lower VRC is associated with higher population prevalence, the predominant CRF02_AG strain in West Africa displayed higher VRC than other prevalent strains suggesting that VRC alone does not explain population prevalence. The study identified viral and host genetic determinants of virus replication capacity for HIV-1 CRF02_AG and subtype A respectively, which may have relevance for vaccine strategies.

【 授权许可】

CC BY