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Transmission of HIV-1 CTL Escape Variants Provides HLA-Mismatched Recipients with a Survival Advantage

机译:HIV-1 CTL逃逸变体的传播为HLA不匹配的收件人提供了生存优势

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摘要

One of the most important genetic factors known to affect the rate of disease progression in HIV-infected individuals is the genotype at the Class I Human Leukocyte Antigen (HLA) locus, which determines the HIV peptides targeted by cytotoxic T-lymphocytes (CTLs). Individuals with HLA-B*57 or B*5801 alleles, for example, target functionally important parts of the Gag protein. Mutants that escape these CTL responses may have lower fitness than the wild-type and can be associated with slower disease progression. Transmission of the escape variant to individuals without these HLA alleles is associated with rapid reversion to wild-type. However, the question of whether infection with an escape mutant offers an advantage to newly infected hosts has not been addressed. Here we investigate the relationship between the genotypes of transmitted viruses and prognostic markers of disease progression and show that infection with HLA-B*57/B*5801 escape mutants is associated with lower viral load and higher CD4+ counts.
机译:已知会影响HIV感染者疾病进展速度的最重要的遗传因素之一是I类人类白细胞抗原(HLA)基因座的基因型,它决定了细胞毒性T淋巴细胞(CTL)靶向的HIV肽。例如,具有HLA-B * 57或B * 5801等位基因的个体靶向Gag蛋白的功能重要部分。逃避这些CTL反应的突变体的适应性可能低于野生型,并且可能与疾病进展较慢有关。逃生变体向没有这些HLA等位基因的个体的传播与迅速回复野生型有关。但是,尚未解决用逃逸突变体感染是否为新感染宿主带来优势的问题。在这里,我们调查了传播病毒的基因型与疾病进展的预后标记之间的关系,并表明感染HLA-B * 57 / B * 5801逃逸突变体与病毒载量较低和CD4 +计数较高有关。
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