Pathogenesis And Immunology Of Animal And Human Retroviruses

不同亚型的人类免疫缺陷病毒在感染患者的组织中似乎有不同的传播模式。在涉及a和C亚型病毒株的双重HIV感染患者中，先前注意到C亚型病毒存在于子宫颈和血液中，而a亚型病毒仅存在于血液中。我们假设这些病毒之间包膜序列的差异可能解释了这种不同的器官趋向性。因此，从V1到V3区域的包膜序列被扩增并克隆到感染性分子克隆中。实验室研究表明，与亚型a克隆相比，来自亚型c的序列促进了PBMC培养中更快的复制以及更广泛的HeLa CD4 CCR5细胞融合。A和C克隆在V1和V3区域的两个氨基酸序列差异似乎解释了这些差异。尽管a亚型克隆最初在PBMC中生长缓慢，但在4-6天后，这些病毒生长得更快，并且发现病毒获得了模仿c亚型克隆中发现的突变。这些相同位点的包膜残基在来自世界各地患者的大多数亚型a或亚型c病毒序列中普遍存在。因此，这些数据表明这些序列可能在体内影响感染效率和器官趋向性方面发挥作用。

Human immunodeficiency viruses of various subtypes appear to have different patterns of spread in tissues of infected patients. In a patient with a dual HIV infection involving both subtype- A and C virus strains, it was previously noted that the subtype-C virus was in both the cervix and the blood, whereas subtype-A virus was only in blood. We hypothesized that envelope sequence differences between these viruses might explain this different organ tropism. Therefore, the envelope sequences form V1 through V3 regions were amplified and cloned into infectious molecular clones. Laboratory studies showed that the sequences from subtype-C facilitated faster replication in PBMC cultures as well as more extensive fusion of HeLa CD4 CCR5 cells compared to subtype-A clones. Two amino acid sequence differences between A and C clones in the V1 and V3 regions appeared to account for these differences. Although subtype-A clones initially grew slowly in PBMC, after 4-6 days these viruses grew faster, and it was found that the viruses had acquired mutations mimicking those found in the subtype-C clones. The envelope residues at these same sites were noted to be prevalent in the sequences of most subtype-A or subtype-C viruses from patients in all parts of the world. Therefore, these data suggest a possible role for these sequences in influencing infection efficiency and organ tropism in vivo.