Two-step evolution of HIV-1 budding system leading to pandemic in the human population

The pandemic HIV-1, HIV-1 group M, emerged from a single spillover event of its ancestral lentivirus from a chimpanzee. During human-to-human spread worldwide, HIV-1 diversified into multiple subtypes. Here, our interdisciplinary investigation mainly sheds light on the evolutionary scenario of viral budding system of HIV-1 subtype C (HIV-1C), a most successfully spread subtype. Of the two amino acid motifs for HIV-1 budding, the P(T/S)AP and YPxL motifs, HIV-1C loses the YPxL motif. Our data imply that HIV-1C might lose this motif to evade immune pressure. Additionally, the P(T/S)AP motif, is duplicated dependently of the level of HIV-1 spread in the human population, and >20% of HIV-1C harbored duplicated P(T/S)AP motif. We further show that the duplication of the P(T/S)AP motif is caused by the expansion of the CTG triplet repeat. Altogether, our results suggest that HIV-1 has experienced two-step evolution of viral budding process during human-to-human spread worldwide.

引发全球大流行的人类免疫缺陷病毒1型（HIV-1）M组，起源于其祖先慢病毒从黑猩猩向人类的单次跨物种传播事件。在全球范围内的人际传播过程中，HIV-1演化出多种亚型。本研究通过跨学科研究，重点阐明了传播最为成功的C亚型人类免疫缺陷病毒1型（HIV-1C）的病毒出芽系统演化路径。在HIV-1出芽相关的两类氨基酸基序——P(T/S)AP基序与YPxL基序——中，HIV-1C丢失了YPxL基序。本研究数据提示，HIV-1C可能通过丢失该基序以逃避免疫压力。此外，P(T/S)AP基序的复制情况与HIV-1在人群中的传播水平相关，且超过20%的HIV-1C携带复制型P(T/S)AP基序。本研究进一步证实，P(T/S)AP基序的复制是由CTG三核苷酸重复序列扩增所导致的。综合上述结果，本研究表明HIV-1在全球人际传播过程中，其病毒出芽过程经历了两步演化。