The role of viral coreceptors and enhanced macrophage tropism in human immunodeficiency virus type 1 disease progression.
The role of viral coreceptors and enhanced macrophage tropism in human immunodeficiency virus type 1 disease progression.
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DOI：
10.1071/sh03006
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发表时间：
2004-01-01
期刊：
影响因子：
1.6
通讯作者：
Wesselingh, Steven
中科院分区：
文献类型：
--
作者：
Gorry, Paul R;Sterjovski, Jasminka;Wesselingh, Steven
尽管对病毒多样性、人类免疫缺陷病毒1型（HIV-1）特异性免疫应答和宿主因素对疾病进展的影响进行了大量研究，但我们仍然没有对HIV-1感染的长期发病机制有明确的认识。在大约40 - 50%的感染个体中，CD 4 + T淋巴细胞的快速消耗与病毒辅助受体使用从CCR 5转换为CXCR 4相关。然而，大多数进展为AIDS的感染个体仅携带CCR 5依赖性（R5）病毒株。HIV-1疾病的进展与R5病毒株对单核细胞/巨噬细胞谱系细胞的嗜性增强（增强的M嗜性）相关。然而，导致R5 HIV-1毒株增强M嗜性的潜在分子机制，以及增强M嗜性的HIV-1变体如何导致体内CD 4 + T细胞耗竭尚不清楚。本文综述了HIV-1病毒辅助受体的使用、M嗜性和致病性之间的关系。我们强调的证据支持的假设，增强M嗜性的R5 HIV-1的结果从适应性病毒进化，导致HIV-1的变种，有能力增加利用相对低水平的CCR 5表达在巨噬细胞，通过增加CCR 5的亲和力。证据还表明，这些晚出现的R5病毒株对进入抑制剂的敏感性降低，并增加了导致CD 4 + T淋巴细胞损失的能力。这些变异可能会影响HIV-1疾病的进展，特别是在持续携带R5病毒株的患者中。
Despite numerous studies on the impact of viral diversity, human immunodeficiency virus type 1 (HIV-1)-specific immune responses and host factors on disease progression, we still do not have a firm understanding of the long-term pathogenesis of HIV-1 infection. Rapid depletion of CD4+ T-lymphocytes has been associated with a switch in viral coreceptor usage from CCR5 to CXCR4 in approximately 40 to 50% of infected individuals. However, the majority of infected individuals who progress to AIDS harbour only CCR5-dependent (R5) viral strains. The progression of HIV-1 disease is associated with an enhanced tropism of R5 viral strains for monocyte/macrophage lineage cells (enhanced M-tropism). However, the underlying molecular mechanisms contributing to enhanced M-tropism by R5 HIV-1 strains, and how HIV-1 variants with enhanced M-tropism cause CD4+ T-cell depletion in vivo are unknown. This review examines the relationship between viral coreceptor usage, M-tropism, and pathogenicity of HIV-1. We highlight evidence supporting the hypothesis that enhanced M-tropism of R5 HIV-1 results from adaptive viral evolution, resulting in HIV-1 variants that have increased ability to utilise relatively low levels of CCR5 expressed on macrophages, by way of increased CCR5 affinity. The evidence also suggests that these late-emerging, R5 viral strains have reduced sensitivity to entry inhibitors, and increased ability to cause CD4+ T-lymphocyte loss. These variants are likely to impact HIV-1 disease progression, especially in patients who persistently harbour only R5 viral strains.