EFFECTS OF BETA CHEMOKINES ON REPLICATION OF T CELL TROPIC STRAINS OF HIV 1

β 趋化因子对 HIV 1 热带 T 细胞株复制的影响

• 批准号: 6160755
• 负责人: A KINTER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6160755
• 关键词: G protein; T lymphocyte; calcium flux; chemokine; cytokine receptors; flow cytometry; human immunodeficiency virus 1; human tissue; macrophage; polymerase chain reaction; receptor coupling; tissue /cell culture; virus receptors; virus replication

Macrophage (M)-tropic HIV-1 quasispecies are the predominant strains replicating in vivo at the time of seroconversion and during the asymptomatic stages of HIV infection. In approximately 40% of HIV-infected individuals, T cell (T)-tropic HIV strains emerge as the predominant species during the course of HIV infection; this "shift" to T-tropic strain dominance is associated with rapid CD4+ T-cell decline and rapid disease progression. The purpose of this study was to investigate whether the ligands of the beta-chemokine receptor CCR5 (MIP-1alpha, MIP-1beta and RANTES), which block the entry/replication of macrophage (M)-tropic HIV strains in vitro by interfering with the ability of M-tropic HIV to utilize CCR5 as an entry co-receptor, influence the replication of T-tropic HIV strains. Treatment of CD4+ T cells from certain HIV-infected subjects with beta-chemokines in vitro was found to enhance the emergence or replication of endogenous T-tropic HIV quasispecies. The infection efficiency of low inocula of T-tropic HIV in CD4+ T cells from uninfected donors was dramatically increased by treatment of cells with numerous beta-chemokines, including MCP-1, which is not a CCR5 ligand. RANTES was demonstrated to enhance the entry of T-tropic HIV strains into CD4+ T cells and this effect was dependent on Gi protein-coupled signal transduction; in contrast, its antagonist, aminooxypentane (AOP)-RANTES, inhibited M-tropic entry but did not increase T-tropic HIV entry. These observations suggest that beta-chemokines may play a role in the shift from predominantly M-tropic to T-tropic HIV strain replication in vivo and that the administration of beta-chemokines to HIV-infected subjects for the purpose of limiting the replication and spread of HIV should be approached with caution as such treatment may result in the accelerated emergence of T-tropic HIV strains.

嗜巨噬细胞(M)型HIV-1准种为优势毒株