Centre for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
Centre of Excellence for Health, Immunity, and Infections, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
J Infect Dis. 2021 Dec 15;224(12):2053-2063. doi: 10.1093/infdis/jiab253.
Understanding the genetic interplay between human hosts and infectious pathogens is crucial for how we interpret virulence factors. Here, we tested for associations between HIV and host genetics, and interactive genetic effects on viral load (VL) in HIV-positive antiretroviral treatment-naive clinical trial participants.
HIV genomes were sequenced and the encoded amino acid (AA) variants were associated with VL, human single nucleotide polymorphisms (SNPs), and imputed HLA alleles using generalized linear models with Bonferroni correction.
Human (388 501 SNPs) and HIV (3010 variants) genetic data were available for 2122 persons. Four HIV variants were associated with VL (P < 1.66 × 10-5). Twelve HIV variants were associated with a range of 1-512 human SNPs (P < 4.28 × 10-11). We found 46 associations between HLA alleles and HIV variants (P < 1.29 × 10-7). HIV variants and immunotypes when analyzed separately were associated with lower VL, whereas the opposite was true when analyzed in concert. Epitope binding predictions supported our observations.
Our results show the importance of immunotype specificity on viral antigenic determinants, and the identified genetic interplay emphasizes that viral and human genetics should be studied in the context of each other.Clinical Trials Registration: NCT00867048.
了解人类宿主与传染性病原体之间的遗传相互作用对于我们如何解释毒力因素至关重要。在这里，我们测试了 HIV 与宿主遗传学之间的关联，以及 HIV 阳性、未接受抗逆转录病毒治疗的临床试验参与者中病毒载量 (VL) 的交互遗传效应。
对 HIV 基因组进行测序，并使用广义线性模型和 Bonferroni 校正，将编码的氨基酸 (AA) 变体与 VL、人类单核苷酸多态性 (SNP) 和推断的 HLA 等位基因相关联。
2122 人提供了人类 (388501 个 SNP) 和 HIV (3010 个变体) 的遗传数据。有 4 个 HIV 变体与 VL 相关 (P < 1.66 × 10-5)。有 12 个 HIV 变体与 1-512 个人类 SNP 相关 (P < 4.28 × 10-11)。我们发现了 46 个 HLA 等位基因与 HIV 变体之间的关联 (P < 1.29 × 10-7)。当分别分析免疫型和 HIV 变体时，它们与较低的 VL 相关，而当协同分析时则相反。表位结合预测支持了我们的观察结果。
我们的结果表明免疫型特异性对病毒抗原决定簇的重要性，并且所确定的遗传相互作用强调病毒和人类遗传学应该相互关联地进行研究。临床试验注册：NCT00867048。
