Intrapatient alterations in the human immunodeficiency virus type 1 gp120 V1V2 and V3 regions differentially modulate coreceptor usage, virus inhibition by CC/CXC chemokines, soluble CD4, and the b12 and 2G12 monoclonal antibodies
Intrapatient alterations in the human immunodeficiency virus type 1 gp120 V1V2 and V3 regions differentially modulate coreceptor usage, virus inhibition by CC/CXC chemokines, soluble CD4, and the b12 and 2G12 monoclonal antibodies
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DOI：
10.1128/jvi.78.1.524-530.2004
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发表时间：
2004-01-01
影响因子：
5.4
通讯作者：
Paxton, WA
中科院分区：
文献类型：
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作者：
Nabatov, AA;Pollakis, G;Paxton, WA
我们研究了人类免疫缺陷病毒 1 型 (HIV-1) 嵌合病毒的 gp120 V1V2 和 V3 包膜区域的改变，以更好地绘制哪些基因改变与 HIV-1 疾病进展相关的特定病毒表型相关。研究的 V1V2 和 V3 区域基于从患有进展性 HIV-1 疾病的个体中分离出的病毒。较高的 V3 电荷与 CXCR4 的使用相关，但仅当在特定的 V1V2 和 V3 N 连接糖基化背景下考虑时。当病毒获得 R5X4 双重向性时，无论其 V3 电荷如何，它都会对 RANTES 的抑制具有高度抵抗力，并对 SDF-1alpha 的抑制高度敏感。具有较高 V3 正电荷的 R5 病毒对 RANTES 的抑制更敏感，而具有较高 V3 正电荷的 R5X4 双向病毒对 SDF-1alpha 的抑制更具有抵抗力。 V3 N-连接糖基化事件的丢失使得病毒对 SDF-1α 的抑制具有更强的抵抗力。 V1V2和V3区域的相同改变影响可溶性CD4以及单克隆抗体b12和2G12中和病毒的程度，但不影响单克隆抗体2F5。这些结果进一步确定了 HIV-1 V1V2 和 V3 区域内的一组复杂的改变，这些改变可以通过改变辅助受体的使用、CC/CXC 趋化因子抑制、CD4 结合和抗体中和在宿主中进行选择。
We studied human immunodeficiency virus type 1 (HIV-1) chimeric viruses altering in their gp120 V1V2 and V3 envelope regions to better map which genetic alterations are associated with specific virus phenotypes associated with HIV-1 disease progression. The V1V2 and V3 regions studied were based on viruses isolated from an individual with progressing HIV-1 disease. Higher V3 charges were linked with CXCR4 usage, but only when considered within a specific V1V2 and V3 N-linked glycosylation context. When the virus gained R5X4 dual tropism, irrespective of its V3 charge, it became highly resistant to inhibition by RANTES and highly sensitive to inhibition by SDF-1alpha. R5 viruses with higher positive V3 charges were more sensitive to inhibition by RANTES, while R5X4 dualtropic viruses with higher positive V3 charges were more resistant to inhibition by SDF-1alpha. Loss of the V3 N-linked glycosylation event rendered the virus more resistant to inhibition by SDF-1alpha. The same alterations in the V1V2 and V3 regions influenced the extent to which the viruses were neutralized with soluble CD4, as well as monoclonal antibodies b12 and 2G12, but not monoclonal antibody 2F5. These results further identify a complex set of alterations within the V1V2 and V3 regions of HIV-1 that can be selected in the host via alterations of coreceptor usage, CC/CXC chemokine inhibition, CD4 binding, and antibody neutralization.