Cornelissen M, Hogervorst E, Zorgdrager F, Hartman S, Goudsmit J
Human Retrovirus Laboratory, Academic Medical Centre, Amsterdam, The Netherlands.
AIDS Res Hum Retroviruses. 1995 Oct;11(10):1169-75. doi: 10.1089/aid.1995.11.1169.
The prevalence of HIV-1 sequences of the envelope domains V1V2 and V3 was analyzed by RT-PCR amplification. Two distinct biological phenotypes of HIV-1 have been described: the nonsyncytium-inducing (NSI) phenotype, best characterized by the inability to infect MT-2 cells, and the syncytium-inducing phenotype (SI), with the ability to infect MT-2 cells. Viral phenotype SI has been associated with HIV pathogenesis. The presence of positively charged amino acids at position 306 and 320 in the V3 domain of gp120 has been shown to be required for the support of the SI phenotype. In addition, V2 elongation and relocation of N-glycosylation sites were postulated to herald an NSI to SI phenotype switch. The present study was designed to assess the stability of an elongated V2 region with relocated N-glycosylation sites observed in SI isolates compared to NSI isolates. Eleven isolates with the SI phenotype and 19 isolates with the NSI phenotype were included in the study. Nine of the SI and 1 of the NSI isolates had a positively charged residue at position 306 or 320 (p < 0.001) in the V3 domain as assessed by direct sequencing of the viral RNA. In contrast, elongation and/or relocation of N-glycosylation sites of the V2 variable region were not found to be a consistent genetic feature of the SI phenotype. However, SI isolates had more positively charged amino acid residues in the hypervariable V2 region compared with NSI isolates. In one of the two SI isolates lacking positively charged amino acids at positions 306 or 320 in the V3 loop an elongation of 26 amino acids with 4 additional N-linked glycosylation sites was observed in the V2 region. This is consistent with the theory that elongation of V2 may be transiently required for SI conversion. These results suggest that maintenance of the SI phenotype requires positively charged amino acids in V3 in the majority of the virus population, but not an elongated V2 region with added or relocated N-linked glycosylation sites. Although increased charged residues in the V2 region may contribute.
通过逆转录聚合酶链反应（RT-PCR）扩增分析了HIV-1包膜结构域V1V2和V3序列的流行情况。已描述了HIV-1的两种不同生物学表型：非融合诱导（NSI）表型，其最显著特征是无法感染MT-2细胞；以及融合诱导表型（SI），具有感染MT-2细胞的能力。病毒表型SI与HIV发病机制有关。已证明gp120的V3结构域中306位和320位带正电荷的氨基酸的存在是支持SI表型所必需的。此外，V2延长和N-糖基化位点的重新定位被认为预示着NSI向SI表型的转变。本研究旨在评估与NSI分离株相比，在SI分离株中观察到的具有重新定位的N-糖基化位点的延长V2区域的稳定性。该研究纳入了11株具有SI表型的分离株和19株具有NSI表型的分离株。通过对病毒RNA进行直接测序评估，9株SI分离株和1株NSI分离株在V3结构域的306位或320位有带正电荷的残基（p<0.001）。相比之下，未发现V2可变区N-糖基化位点的延长和/或重新定位是SI表型的一致遗传特征。然而，与NSI分离株相比，SI分离株在高变V2区域有更多带正电荷的氨基酸残基。在V3环中306位或320位缺乏带正电荷氨基酸的两株SI分离株之一中，在V2区域观察到26个氨基酸的延长以及4个额外的N-连接糖基化位点。这与V2延长可能是SI转化所暂时需要的这一理论一致。这些结果表明，在大多数病毒群体中，维持SI表型需要V3中带正电荷的氨基酸，但不需要具有添加或重新定位的N-连接糖基化位点的延长V2区域。尽管V2区域中增加的带电荷残基可能有作用。
