Saha Kunal, Yan Hui, Nelson Julie A E, Zerhouni-Layachi Bouchra
Department of Pediatrics and Molecular Virology, Immunology and Medical Genetics, Children's Research Institute and Ohio State University Medical Center, Columbus, 43205, USA.
Virology. 2005 Jun 20;337(1):30-44. doi: 10.1016/j.virol.2005.04.003.
Truncation of the envelope cytoplasmic tail has enabled FIV, SIV, and some laboratory HIV-1 strains to acquire broader cellular tropism and enhanced fusogenicity. Here we have characterized a primary CD4-independent HIV-1 isolate (92UG046-T8) with a truncated cytoplasmic tail that was able to infect and induce syncytia in primary lymphocytes from human, chimpanzee, and monkey, as well as CD4-negative cell lines from human and monkey. Increased syncytia were also noticeable with 293 cells expressing the cloned envelope from the 92UG046-T8 isolate suggesting envelope-mediated cellular fusion. Except pooled serum from HIV-1-infected individuals, monoclonal anti-envelope antibodies or antibodies/antagonists against CD4, CXCR4, and CCR5 were not able to prevent infection by the 92UG046-T8 isolate. This is the first report showing a primary HIV-1 variant with truncated cytoplasmic tail which is highly fusogenic and can infect a broad range of cells from human and non-human origins. In vivo evolution of similar HIV-1 mutants may have important implications in AIDS pathogenesis.
包膜细胞质尾的截短使猫免疫缺陷病毒（FIV）、猴免疫缺陷病毒（SIV）以及一些实验室的人类免疫缺陷病毒1型（HIV-1）毒株获得了更广泛的细胞嗜性和增强的融合能力。在此，我们对一株具有截短细胞质尾的原发性不依赖CD4的HIV-1分离株（92UG046-T8）进行了特性分析，该毒株能够感染并在人、黑猩猩和猴的原代淋巴细胞以及人和猴的CD4阴性细胞系中诱导形成多核巨细胞。在表达来自92UG046-T8分离株的克隆包膜的293细胞中，多核巨细胞的数量也明显增加，提示包膜介导的细胞融合。除了来自HIV-1感染个体的混合血清外，单克隆抗包膜抗体或针对CD4、CXCR4和CCR5的抗体/拮抗剂均无法阻止92UG046-T8分离株的感染。这是首次报道一种具有截短细胞质尾的原发性HIV-1变异体，其具有高度融合性，能够感染来自人类和非人类的多种细胞。类似HIV-1突变体在体内的进化可能对艾滋病发病机制具有重要意义。
