Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Infect Genet Evol. 2020 Jun;80:104216. doi: 10.1016/j.meegid.2020.104216. Epub 2020 Jan 30.
Bone marrow stromal cell antigen 2 (BST2 or tetherin) is a host-encoded, interferon-inducible antiviral restriction factor which blocks the release of enveloped viruses. Few studies have assessed the role of BST2 polymorphisms on HIV-1 acquisition or disease progression in sub-Saharan Africa. This study investigated the frequency of four HIV-1-associated BST2 variants rs3217318, rs12609479, rs10415893 and rs113189798 in uninfected and HIV-1 infected black South Africans. Homozygosity for the rs12609479-A minor allele, previously associated with decreased HIV-1 acquisition risk, was underrepresented in HIV-1 uninfected black South Africans (2%) compared to reference African (9%) and in particular European populations (61%) (p = .047 and p < .0001, respectively). To determine if any of these gene variants influenced HIV-1 control in the absence of antiretroviral treatment (ART), we compared HIV-1 infected ART-naïve progressors [n = 72] and controllers [n = 71], the latter includes elite controllers [EC: n = 23; VL < 50 RNA copies/ml]. Heterozygosity for the rs12609479 SNP (G/A) was enriched in progressors compared to ECs (47.2% vs 21.7%, OR = 3.50 [1.16-10.59], p = .03), while rs113189798 heterozygosity (A/G) showed a strong trend of overrepresentation in ECs compared to progressors (47.8% vs 26.4%, OR = 0.39 [0.14-1.04], p = .07). Heterozygosity for the promoter indel rs3217318 (i19/Δ19) was associated with a faster rate of CD4 T-cell decline in progressors (p = .0134). Carriage of the rs3217318 (i19/Δ19), rs12609479 (G/G), rs10415893(G/A) and rs113189798 (A/G) combined genotype, denoted as i19Δ19 GG GA AG, was associated with significantly higher CD4 T-cell counts in progressors (p = .03), a finding predominantly driven by the _GG_AG combination. Our data suggest that the possession of select BST2 genotype combinations may be implicated in HIV-1 disease progression and natural spontaneous control.
骨髓基质细胞抗原 2（BST2 或 tetherin）是一种宿主编码的干扰素诱导的抗病毒限制因子，可阻止包膜病毒的释放。很少有研究评估 BST2 多态性在撒哈拉以南非洲的 HIV-1 获得或疾病进展中的作用。本研究调查了未感染和感染 HIV-1 的南非黑人中四种与 HIV-1 相关的 BST2 变体 rs3217318、rs12609479、rs10415893 和 rs113189798 的频率。先前与 HIV-1 获得风险降低相关的 rs12609479-A 等位基因纯合子在未感染 HIV-1 的南非黑人（2%）中代表性不足，而在参考非洲（9%）和特别是欧洲人群（61%）中代表性不足（p = 0.047 和 p < 0.0001，分别）。为了确定这些基因变体是否会影响没有抗逆转录病毒治疗（ART）的 HIV-1 控制，我们比较了 HIV-1 感染的未经治疗的进展者 [n = 72] 和控制器 [n = 71]，后者包括精英控制器 [EC：n = 23；VL < 50 RNA 拷贝/ml]。与 EC 相比，rs12609479 SNP（G/A）杂合子在进展者中更为丰富（47.2%比 21.7%，OR = 3.50 [1.16-10.59]，p = 0.03），而 rs113189798 杂合子（A/G）在 EC 中比进展者中更具代表性（47.8%比 26.4%，OR = 0.39 [0.14-1.04]，p = 0.07）。启动子插入缺失 rs3217318（i19/Δ19）杂合子与进展者中 CD4 T 细胞下降速度更快相关（p = 0.0134）。携带 rs3217318（i19/Δ19）、rs12609479（G/G）、rs10415893（G/A）和 rs113189798（A/G）的组合基因型，记为 i19Δ19 GG GA AG，与进展者中 CD4 T 细胞计数显著增加相关（p = 0.03），这一发现主要由 _GG_AG 组合驱动。我们的数据表明，某些 BST2 基因型组合的存在可能与 HIV-1 疾病进展和自然自发控制有关。
