Pathogenesis And Immunology Of Animal And Human Retroviruses

各种亚型的人类免疫缺陷病毒在感染患者的组织中似乎具有不同的传播模式。在涉及A亚型和C亚型病毒株的双重HIV感染的患者中，先前注意到C亚型病毒在宫颈和血液中，而A亚型病毒仅在血液中。我们假设这些病毒之间的包膜序列差异可能解释这种不同的器官嗜性。因此，从V1到V3区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，亚型C的序列促进了PBMC培养物中更快的复制以及HeLa CD 4 CCR 5细胞更广泛的融合。在V1和V3区域中A和C克隆之间的两个氨基酸序列差异似乎解释了这些差异。尽管亚型A克隆最初在PBMC中生长缓慢，但在4-6天后，这些病毒生长更快，并且发现病毒已经获得了模仿在亚型C克隆中发现的那些的突变。这些相同位点的包膜残基在世界各地患者的大多数A亚型或C亚型病毒序列中普遍存在。因此，这些数据表明这些序列在影响体内感染效率和器官嗜性中可能起作用。

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.