Wang Bin, Mikhail Meriet, Dyer Wayne B, Zaunders John J, Kelleher Anthony D, Saksena Nitin K
Retroviral Genetics Laboratory, Center for Virus Research, Westmead Millennium Institute, Westmead, NSW 2145, Australia.
Virology. 2003 Jul 20;312(1):135-50. doi: 10.1016/s0042-6822(03)00159-4.
It is universally acknowledged that genetic diversity is a hallmark of HIV-1 infection, and it is one of the traits that has considerably hampered the development of an effective vaccine. In a study of full-length HIV-1 genomic sequences (>9 kb), we show unique evidence for complete absence of viral evolution in an individual with truly nonprogressive infection. Gross gene defects were not detected, but the state of replication incompetence was attributed to the presence of stop codons in the structural genes gag p17 and p24 and in pol RT, which emerged as a consequence of G-A hypermutation. These inactivating mutations may have occurred early, soon after infection, during the clonal stage of primary viral replication, since these are the sole archival strains present today. This genetic homogeneity, with <1% variation between strains over an 8-year period, suggests that only limited proviral integration events occurred in this patient. Further study on the antigenic properties of this strain may assist in the development of HIV vaccines and therapeutics.
人们普遍认为，基因多样性是HIV-1感染的一个标志，也是严重阻碍有效疫苗研发的特征之一。在一项对全长HIV-1基因组序列（>9 kb）的研究中，我们展示了独特的证据，表明在一名真正非进行性感染的个体中完全不存在病毒进化。未检测到明显的基因缺陷，但复制无能力状态归因于结构基因gag p17和p24以及pol RT中存在终止密码子，这是G-A超突变的结果。这些失活突变可能在感染后不久的原发性病毒复制克隆阶段早期就已发生，因为这些是目前仅有的存档毒株。这种基因同质性，即菌株在8年期间的变异小于1%，表明该患者仅发生了有限的前病毒整合事件。对该毒株抗原特性的进一步研究可能有助于HIV疫苗和治疗方法的研发。
