Human immunodeficiency virus type 1 (HIV-1)-induced GRO-alpha production stimulates HIV-1 replication in macrophages and T lymphocytes.
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 CXCR4. GRO-alpha then fed back and stimulated HIV-1 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.
Lane
B R
BR
Department of Internal Medicine, Divisions of Infectious Diseases, University of Michigan Medical Center, Ann Arbor, MI 48109-0640, USA.
Strieter
R M
RM
Coffey
M J
MJ
Markovitz
D M
DM
D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis*; D006133:Growth Substances / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000821:virology*; D019718:Receptors, CXCR4 / Q000502:physiology; D023063:Receptors, Interleukin-8B / Q000502:physiology; D013601:T-Lymphocytes / Q000821:virology*; D014779:Virus Replication
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D015699:HIV Envelope Protein gp120; D036341:Intercellular Signaling Peptides and Proteins; D019718:Receptors, CXCR4; D023063:Receptors, Interleukin-8B