Foley B, Pan H, Buchbinder S, Delwart E L
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico 87501, USA.
AIDS Res Hum Retroviruses. 2000 Oct 10;16(15):1463-9. doi: 10.1089/088922200750005985.
HIV-1 envelope sequence variants were RT-PCR amplified from serum samples cryopreserved in San Francisco in 1978-1979. The HIV-1 subtype B env V3-V5 sequences from four homosexual men clustered phylogenetically, with a median nucleotide distance of 2.8%, reflecting a recent common origin. These early U.S. HIV-1 env variants mapped close to the phylogenetic root of the subtype B tree while env variants collected in the United States throughout the 1980s and 1990s showed, on average, increasing genetic diversity and divergence from the subtype B consensus sequence. These results indicate that the majority of HIV-1 currently circulating in the United States may be descended from an initial introduction and rapid spread during the mid- to late 1970s of subtype B viruses with limited variability (i.e., a founder effect). As expected from the starburst-shaped phylogeny of HIV-1 subtype B, contemporary U.S. strains were, on average, more closely related at the nucleic acid and amino acid levels to the earlier 1978-1979 env variants than to each other. The growing levels of HIV-1 genetic diversity, one of multiple obstacles in designing a protective vaccine, may therefore be mitigated by using epidemic founding variants as antigenic strains for protection against contemporary strains.
从1978 - 1979年保存在旧金山的血清样本中,通过逆转录聚合酶链反应(RT-PCR)扩增出HIV-1包膜序列变体。来自四名同性恋男性的HIV-1 B亚型env V3 - V5序列在系统发育上聚类,中位核苷酸距离为2.8%,这反映了它们近期有共同起源。这些早期的美国HIV-1 env变体在系统发育树上的位置靠近B亚型树的根部,而在整个20世纪80年代和90年代在美国收集的env变体平均显示出遗传多样性增加,并且与B亚型共有序列的差异越来越大。这些结果表明,目前在美国传播的大多数HIV-1可能源自20世纪70年代中后期B亚型病毒的初次引入和快速传播,且变异性有限(即奠基者效应)。正如HIV-1 B亚型呈星爆状系统发育所预期的那样,当代美国毒株在核酸和氨基酸水平上平均与1978 - 1979年早期的env变体比它们彼此之间的关系更为密切。因此,设计保护性疫苗的多重障碍之一——HIV-1遗传多样性的不断增加,可能通过使用疫情起始变体作为抗原株来预防当代毒株而得到缓解。