Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in southern Africa
Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in southern Africa
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DOI：
10.1128/jvi.01730-06
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发表时间：
2006-12-01
影响因子：
5.4
通讯作者：
Montefiori, David C.
中科院分区：
文献类型：
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作者：
Li, Ming;Salazar-Gonzalez, Jesus F.;Montefiori, David C.
通过克隆、测序和鉴定来自南非和赞比亚18个急性和早期异性获得性感染的功能性gp160基因，创建了C亚型人类免疫缺陷病毒1型(HIV-1)环境伪型病毒的标准小组。一般来说，与新传播的B亚型病毒相比，这些克隆的gp120区域较短(V1和V4最明显)，糖基化程度较低，但与慢性C亚型病毒相比，糖基化程度较低，但长度没有差异。Gp120s还表现出V3的低氨基酸序列变异性(12%)和紧邻V3下游的高变异性(39%)，这一特征与新传播的B亚型病毒和这两个亚型的慢性病毒相同。在荧光素酶报告基因检测中，所有克隆作为Env假型病毒时，都具有R5表型，并且在对HIV-1阳性血浆中和的敏感性方面与原始分离株相似。用多亚型血浆板获得的结果表明，感染的中和抗体反应中有部分亚型偏爱。这些克隆都是典型的C亚型，它们都对2G12抗性(与295位N-糖基化缺失有关)，大多数对2F5抗性，但都对4E10敏感，许多克隆对免疫球蛋白G1b12敏感。最后，gp120的CD4诱导的辅受体结合区的保守中和表位很难获得，并且很难与包膜伪型病毒上的可溶性CD4诱导和稳定。这些结果说明了C亚型HIV-1的关键遗传和抗原性，可能会影响候选疫苗的设计和测试。这些gp160克隆的一个子集适合用作参考试剂，以促进疫苗引发的中和抗体反应的标准化评估。
A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Zambia. In general, the gp120 region of these clones was shorter (most evident in V1 and V4) and less glycosylated compared to newly transmitted subtype B viruses, and it was underglycosylated but no different in length compared to chronic subtype C viruses. The gp120s also exhibited low amino acid sequence variability (12%) in V3 and high variability (39%) immediately downstream of V3, a feature shared with newly transmitted subtype B viruses and chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a luciferase reporter gene assay, all clones possessed an R5 phenotype and resembled primary isolates in their sensitivity to neutralization by HIV-1-positive plasmas. Results obtained with a multisubtype plasma panel suggested partial subtype preference in the neutralizing antibody response to infection. The clones were typical of subtype C in that all were resistant to 2G12 (associated with loss of N-glycosylation at position 295) and most were resistant to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor binding domain of gp120 were poorly accessible and were difficult to induce and stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines. A subset of these gp160 clones are suitable for use as reference reagents to facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.