Mammano F, Salvatori F, Ometto L, Panozzo M, Chieco-Bianchi L, De Rossi A
Institute of Oncology, Interuniversity Center for Cancer Research, University of Padua, Italy.
J Virol. 1995 Jan;69(1):82-92. doi: 10.1128/JVI.69.1.82-92.1995.
The third variable region (V3) of the envelope protein of human immunodeficiency virus type 1 (HIV-1) contains group- and type-specific epitopes for neutralizing antibodies and contains determinants involved in viral tropism and syncytium-inducing (SI) activity. We studied the in vivo relationship between V3 sequences and viral phenotypes in 24 perinatally HIV-1-infected children. To avoid in vitro selection of intrapatient minor variants, genetic studies were performed directly on uncultured peripheral blood mononuclear cells (PBMC), and the tropisms of HIV-1 isolates were evaluated by culturing patients' PBMC directly with monocyte-derived macrophages, lymphocytes, and MT-2 cells. According to their phenotypes, we could define five types of primary isolates: (i) non-syncytium-inducing (NSI) macrophagetropic, (ii) NSI macrophage-lymphotropic, (iii) NSI lymphotropic, (iv) SI lympho-T-cell line-tropic, and (v) SI pleiotropic. The SI viral phenotype was correlated with a more advanced status of disease. Genetic analysis of intrapatient molecular variants revealed that no relationship between the degree of intrapatient V3 variability and the pattern of viral tropism existed; moreover, within a single patient, the values for V3 variability between CD4+ lymphocytes and CD14+ monocytes were similar, thus suggesting that in vivo variability of the monocytotropic variants is more extensive than previously appreciated. A comparison between the intrapatient major variants and the phenotype of primary isolates disclosed that a negatively charged amino acid at residue site 25 was associated with an NSI macrophage- and macrophage-lymphotropic viral phenotype. Finally, by comparing the V3 sequences derived from our study population with those of several prototypes, we observed that the majority of isolates circulating in Italy are related to the North American subtype B macrophagetropic isolates.
人类免疫缺陷病毒1型（HIV-1）包膜蛋白的第三个可变区（V3）含有中和抗体的组特异性和型特异性表位，并含有与病毒嗜性及合胞体诱导（SI）活性相关的决定簇。我们研究了24名围产期感染HIV-1儿童体内V3序列与病毒表型之间的关系。为避免体外选择患者体内的次要变异体，直接对未培养的外周血单个核细胞（PBMC）进行了基因研究，并通过将患者的PBMC直接与单核细胞衍生的巨噬细胞、淋巴细胞及MT-2细胞共培养来评估HIV-1分离株的嗜性。根据其表型，我们可将原始分离株分为五种类型：（i）非合胞体诱导（NSI）巨噬细胞嗜性，（ii）NSI巨噬细胞-淋巴细胞嗜性，（iii）NSI淋巴细胞嗜性，（iv）SI淋巴细胞-T细胞系嗜性，以及（v）SI多嗜性。SI病毒表型与疾病的更晚期状态相关。对患者体内分子变异体的基因分析显示，患者体内V3变异程度与病毒嗜性模式之间不存在相关性；此外，在单个患者体内，CD4+淋巴细胞与CD14+单核细胞之间的V3变异值相似，因此表明嗜单核细胞变异体的体内变异性比之前所认识到的更为广泛。对患者体内主要变异体与原始分离株表型之间的比较揭示，第25位残基处带负电荷的氨基酸与NSI巨噬细胞及巨噬细胞-淋巴细胞嗜性病毒表型相关。最后，通过将我们研究人群的V3序列与几种原型的序列进行比较，我们观察到在意大利流行的大多数分离株与北美B亚型巨噬细胞嗜性分离株相关。
