Abstract
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.
Highlights
The Human immunodeficiency virus type 1 (HIV-1) epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence
Data analysis viral replication capacity (VRC) of patient-derived chimeric viruses were compared based on HIV-1 subtype classification and geographical region using either the Student’s t-test or Mann–Whitney U test if two groups were compared, or ANOVA with Tukey post-hoc tests where more than two groups were compared
ANOVA was used to test for differences in VRC across each group of the major Human leucocyte antigen (HLA) class I genes (A, B and C) for participants infected with subtype A1 from East Africa, while the Student’s t-test was HIV‐1 subtype diversity and distribution A high level of subtype diversity was observed in West Africa, consistent with previous reports [6, 49]
Summary
The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Sub-Saharan Africa bears the brunt of the HIV-1 epidemic with approximately 70% of the estimated people living with the virus globally [1]. The epidemic in sub-Saharan Africa is heterogeneous, with significant regional differences in prevalence and multiple HIV-1. In East Africa, HIV-1 prevalence rates are higher at above 5% [8, 9], with subtypes A1, C and D and their recombinants co-circulating. Multiple factors account for the heterogeneity of HIV prevalence and disease progression rates across sub-Saharan Africa, including sociocultural factors such as male circumcision practices, socioeconomic factors, coinfections, microbiota, host genetic and viral factors [10,11,12,13,14,15]. Considering that curtailing HIV transmission and providing optimal treatment remain formidable public health challenges worldwide, a better understanding of the viral factors that enhance transmission efficiency or the rate of disease progression following infection may be required for novel interventions such as vaccines [16]
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