HIV-1 downregulates human leukocyte antigen A (HLA-A) and HLA-B from the surface of infected cells primarily to evade CD8 T cell recognition. HLA-C was thought to remain on the cell surface and bind inhibitory killer immunoglobulin-like receptors, preventing natural killer (NK) cell-mediated suppression. However, a recent study found HIV-1 primary viruses have the capacity to downregulate HLA-C. The goal of this study was to assess the heterogeneity of HLA-A, HLA-B, and HLA-C downregulation among full-length primary viruses from six chronically infected and six newly infected individuals from transmission pairs and to determine whether transmitted/founder variants exhibit common HLA class I downregulation characteristics. We measured HLA-A, HLA-B, HLA-C, and total HLA class I downregulation by flow cytometry of primary CD4 T cells infected with 40 infectious molecular clones. Primary viruses mediated a range of HLA class I downregulation capacities (1.3- to 6.1-fold) which could differ significantly between transmission pairs. Downregulation of HLA-C surface expression on infected cells correlated with susceptibility to in vitro NK cell suppression of virus release. Despite this, transmitted/founder variants did not share a downregulation signature and instead were more similar to the quasispecies of matched donor partners. These data indicate that a range of viral abilities to downregulate HLA-A, HLA-B, and HLA-C exist within and between individuals that can have functional consequences on immune recognition.

IMPORTANCE Subtype C HIV-1 is the predominant subtype involved in heterosexual transmission in sub-Saharan Africa. Authentic subtype C viruses that contain natural sequence variations throughout the genome often are not used in experimental systems due to technical constraints and sample availability. In this study, authentic full-length subtype C viruses, including transmitted/founder viruses, were examined for the ability to disrupt surface expression of HLA class I molecules, which are central to both adaptive and innate immune responses to viral infections. We found that the HLA class I downregulation capacity of primary viruses varied, and HLA-C downregulation capacity impacted viral suppression by natural killer cells. Transmitted viruses were not distinct in the capacity for HLA class I downregulation or natural killer cell evasion. These results enrich our understanding of the phenotypic variation existing among natural HIV-1 viruses and how that might impact the ability of the immune system to recognize infected cells in acute and chronic infection.

HIV-1从受感染细胞表面下调人类白细胞抗原A（HLA-A）和HLA-B，主要是为了逃避CD8 T细胞识别。人们认为HLA-C保留在细胞表面并结合抑制性杀手免疫球蛋白样受体，从而阻止了自然杀伤（NK）细胞介导的抑制作用。但是，最近的一项研究发现，HIV-1原发性病毒具有下调HLA-C的能力。这项研究的目的是评估来自传播对的六个慢性感染的个体和六个新感染的个体的全长原代病毒中HLA-A，HLA-B和HLA-C下调的异质性，并确定是否存在传播/基础变异表现出常见的HLA I类下调​​特性。我们测量了HLA-A，HLA-B，HLA-C，流式细胞术检测被40个感染性分子克隆感染的原代CD4 T细胞的总HLA I类下调​​。原发病毒介导了一系列HLA I类下调​​能力（1.3到6.1倍），这在传播对之间可能有显着差异。HLA-C表面表达在受感染细胞上的下调与易感性相关体外NK细胞抑制病毒释放。尽管如此，传播/创始人变异没有共享下调签名，而是与匹配的捐助伙伴的准物种更相似。这些数据表明，个体内和个体之间存在一定范围的病毒下调HLA-A，HLA-B和HLA-C的能力，这会对免疫识别产生功能性影响。

重要性C型亚型HIV-1是撒哈拉以南非洲地区异性传播的主要亚型。由于技术上的限制和样品的可获得性，在整个基因组中包含自然序列变异的真实C型亚型病毒通常不用于实验系统。在这项研究中，检查了包括传播/基础病毒在内的真实的全长C型亚型病毒破坏HLA I类分子表面表达的能力，而HLA I类分子对于病毒感染的适应性免疫和先天性免疫应答都是至关重要的。我们发现，一级病毒的HLA I类下调​​能力各不相同，而HLA-C下调能力影响了自然杀伤细胞对病毒的抑制作用。传播的病毒在HLA I类下调​​或自然杀伤细胞逃逸的能力方面没有区别。