Host Genomic Factors in Infectious Disease Susceptibility

尽管对感染的流行病学和行为风险因素有了全面的了解，但世界范围内的艾滋病毒感染率仍然非常高。这些风险因素具有不同的性质，包括高风险性行为、艾滋病毒的地理流行率、传播者体内的病毒载量、包皮环切情况和其他性传播感染，如单纯疱疹病毒2型感染。然而，在非常相似的风险环境中，只有一些人受到感染，而其他人则没有，这一观察结果仍然有些令人费解。在这个项目中，我们的目标是使用新的精确GWAS方法来发现宿主基因组多态性，这些多态性决定了对HIV的保护和易感性。我们对高风险HVTN 505疫苗队列以及其他队列中仔细匹配的HIV感染者进行了两阶段完全基于NGS的分析。我们使用我们的数据集来探索HVTN 505试验中宿主遗传对疫苗效力的影响这一单独的额外问题。我们发现了多个多态性，具有非常高的意义，决定保护和易感性艾滋病毒的收购。我们发现HVTN 505在30%具有特定基因型的队列中有效。

World-wide HIV infection rates remain remarkably high despite a thorough understanding of the epidemiological and behavioral risk factors for acquisition. These risk factors are of a diverse nature and include high risk sexual practices, geographical HIV prevalence, virus load in the transmitter, circumcision status and other sexually transmitted infections such as herpes simplex virus type 2 infection. However, the observation that in very similar risk settings only some persons become infected whereas others do not remains somewhat enigmatic. In this project we aim is to used novel precision GWAS approaches to discover host genomic polymorphisms that determine protection from and susceptibility to the acquisition of HIV. We performed a two-stage wholly NGS-based analysis of the high-risk HVTN 505 vaccine cohort as well as carefully matched HIV-infected persons from other cohorts. We used our dataset to explore the separate additional question of host genetic influence on vaccine efficacy in the HVTN 505 trial. We discovered multiple polymorphisms with very high significance that that determine protection from and susceptibility to HIV acquisition. We found that HVTN 505 was efficacious in 30% of the cohort with a specific genotype.