Abstract Pathogen-driven selection and past interbreeding with archaic human lineages have resulted in differences in human leukocyte antigen (HLA)-allele frequencies between modern human populations. Whether or not this variation affects pathogen subtype diversification is unknown. Here we show a strong positive correlation between ethnic diversity in African countries and both human immunodeficiency virus (HIV)-1 p24gag and subtype diversity. We demonstrate that ethnic HLA-allele differences between populations have influenced HIV-1 subtype diversification as the virus adapted to escape common antiviral immune responses. The evolution of HIV Subtype B (HIV-B), which does not appear to be indigenous to Africa, is strongly affected by immune responses associated with Eurasian HLA variants acquired through adaptive introgression from Neanderthals and Denisovans. Furthermore, we show that the increasing and disproportionate number of HIV-infections among African Americans in the USA drive HIV-B evolution towards an Africa-centric HIV-1 state. Similar adaptation of other pathogens to HLA variants common in affected populations is likely.

中文翻译：

---

HIV-1 p24Gag 对现代和古代 HLA 等位基因频率差异的适应有助于病毒亚型多样化


摘要 病原体驱动的选择以及过去与古代人类谱系的杂交导致了现代人类群体之间人类白细胞抗原（HLA）等位基因频率的差异。这种变异是否影响病原体亚型多样化尚不清楚。在这里，我们展示了非洲国家的种族多样性与人类免疫缺陷病毒 (HIV)-1 p24gag 和亚型多样性之间存在很强的正相关性。我们证明，随着病毒适应逃避常见的抗病毒免疫反应，人群之间的种族 HLA 等位基因差异影响了 HIV-1 亚型的多样化。 HIV B 亚型 (HIV-B) 的进化似乎并非非洲本土的，它的进化受到与通过尼安德特人和丹尼索瓦人适应性渗入获得的欧亚 HLA 变体相关的免疫反应的强烈影响。此外，我们发现，美国非裔美国人中 HIV 感染人数的不断增加和不成比例，推动 HIV-B 向以非洲为中心的 HIV-1 状态演变。其他病原体也可能对受影响人群中常见的 HLA 变异产生类似的适应。