Learn Gerald H, Muthui David, Brodie Scott J, Zhu Tuofu, Diem Kurt, Mullins James I, Corey Lawrence
Department of Microbiology, University of Washington, Seattle, Washington 98195, USA.
J Virol. 2002 Dec;76(23):11953-9. doi: 10.1128/jvi.76.23.11953-11959.2002.
Understanding the properties of human immunodeficiency virus type 1 (HIV-1) variants capable of establishing infection is critical to the development of a vaccine against AIDS. Previous studies of men have shown that the HIV-1 env gene is homogeneous early in infection, leading to the suggestion that infection is established by a single transmitted variant. However, we report here that all of eight homosexual men evaluated beginning 3.7 to 9 weeks following onset of symptoms of acute infection harbored diverse virus populations in their blood, with median genetic distances averaging 1.08% in the env C2V5 region and 0.81% in the gag p17 gene. Within another 4.7 to 11 weeks, the variant lineage in env became more homogeneous, while gag sequences continued to diversify. Thus, the homogenization that has been reported to characterize acute infection is actually preceded by the replication of multiple virus variants. This early selective process focuses on viral properties within Env but not Gag p17. Hence, the viral homogeneity observed early in HIV-1 infection results from a selective process that occurs during the establishment of infection.
了解能够引发感染的1型人类免疫缺陷病毒(HIV-1)变体的特性对于开发抗艾滋病疫苗至关重要。先前对男性的研究表明,HIV-1 env基因在感染初期是同质的,这表明感染是由单一传播变体引发的。然而,我们在此报告,在急性感染症状出现后3.7至9周开始评估的8名同性恋男性中,所有人血液中均携带多种病毒群体,env C2V5区域的中位遗传距离平均为1.08%,gag p17基因的中位遗传距离平均为0.81%。在另外4.7至11周内,env中的变体谱系变得更加同质,而gag序列继续多样化。因此,据报道的表征急性感染的同质化实际上是在多种病毒变体复制之后发生的。这个早期选择过程侧重于Env内的病毒特性,而不是Gag p17。因此,HIV-1感染早期观察到的病毒同质性是由感染建立过程中发生的选择过程导致的。