Human immunodeficiency virus type 1 (HIV-1)-induced GRO-α production stimulates HIV-1 replication in macrophages and T lymphocytes

被引:32
作者
Lane, BR
Strieter, RM
Coffey, MJ
Markovitz, DM
机构
[1] Univ Michigan, Med Ctr, Dept Internal Med, Div Infect Dis, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Med Ctr, Div Pulm & Crit Care Med, Dept Internal Med, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Med Ctr, Program Mol & Cellular Biol, Ann Arbor, MI 48109 USA
关键词
D O I
10.1128/JVI.75.13.5812-5822.2001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We examined the early effects of infection by CCR5-using (R5 human immunodeficiency virus [HIV]) and CXCR4-using (X4 HIV) strains of HIV type 1 (HIV-1) on chemokine production by primary human monocyte-derived macrophages (MDM). While R5 HIV, but not X4 HIV, replicated in MDM, we found that the production of the C-X-C chemokine growth-regulated oncogene alpha (GRO-alpha) was markedly stimulated by X4 HIV and, to a much lesser extent, by R5 HIV. HIV-1 gp120 engagement of CXCR4 initiated the stimulation of GRO-alpha production, an effect blocked by antibodies to CXCR1. GRO-alpha then fed back and stimulated HIV-I replication in both MDM and lymphocytes, and antibodies that neutralize GRO-alpha or CXCR2 (the receptor for GRO-alpha) markedly reduced viral replication in MDM and peripheral blood mononuclear cells. Therefore, activation of MDM by HIV-1 gp120 engagement of CXCR4 initiates an autocrine-paracrine loop that may be important in disease progression after the emergence of X4 HIV.
引用
收藏
页码:5812 / 5822
页数:11
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