Human immunodeficiency virus replication induces monocyte chemotactic protein-1 in human macrophages and U937 promonocytic cells. NLM AIDSLINE Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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Human immunodeficiency virus replication induces monocyte chemotactic protein-1 in human macrophages and U937 promonocytic cells.

Blood. 1999 Mar 15;93(6):1851-7. Unique Identifier : AIDSLINE MED/99168972
Mengozzi M; De Filippi C; Transidico P; Biswas P; Cota M; Ghezzi S; Vicenzi E; Mantovani A; Sozzani S; Poli G; AIDS Immunopathogenesis Unit, DIBIT, San Raffaele Scientific; Institute, Milano, Italy.

Abstract: We have recently described a significant correlation between human immunodeficiency virus-1 (HIV-1) RNA replication and monocyte chemotactic protein-1 (MCP-1) levels in the cerebrospinal fluid (CSF) of individuals with the acquired immunodeficiency syndrome (AIDS) with HIV encephalitis (E). Because local macrophages (microglia) are the cells predominantly infected in the brain, we investigated whether in vitro HIV infection affects MCP-1 production in mononuclear phagocytes (MP). MCP-1 secretion and expression were consinstently upregulated over constitutive levels in human monocyte-derived macrophages (MDM) infected with the M-tropic R5 BaL strain of HIV-1. HIV replication was required for this effect, as demonstrated by the absence of chemokine upregulation after infection in the presence of 3'-azido-3'-deoxythimidine (AZT) or cell-exposure to heat-inactivated (triangle up degrees ) virus. MCP-1 induction was not restricted to HIV-1 BaL, but was also observed during productive infection of MDM with two primary isolates differing for entry coreceptor usage and of U937 cells with the X4 HIV-1 MN strain. Based on the observation that exogenous HIV-1 Tat induced MCP-1 expression in astrocytes, we also investigated its role in MDM and U937 cells. Exogenous Tat induced MCP-1 production from MDM in a concentration-dependent manner, however, it was not effective on uninfected U937 cells or on the chronically infected U937-derived cell line U1. Transfection of Tat-expressing plasmids moderately activated HIV expression in U1 cells, but failed to induce MCP-1 expression in this cell line or in uninfected U937 cells. HIV replication-dependent expression of MCP-1 in MP may be of particular relevance for the pathogenesis of HIV infection in nonlymphoid organs such as the brain.
Keywords: JOURNAL ARTICLE Gene Expression Gene Products, tat/GENETICS/PHARMACOLOGY Human HIV-1/*PHYSIOLOGY Lipopolysaccharides/PHARMACOLOGY Macrophages/METABOLISM/*VIROLOGY Monocyte Chemoattractant Protein-1/*BIOSYNTHESIS/GENETICS Mutation RNA, Messenger/METABOLISM Support, Non-U.S. Gov't Transfection U937 Cells/METABOLISM/*VIROLOGY *Virus ReplicationKWDjournalarticlegeneexpressiongeneproducts,tat/genetics/pharmacologyhumanhiv-1/KWDphysiologylipopolysaccharides/pharmacologymacrophages/metabolism/KWDvirologymonocytechemoattractantprotein-1/KWDbiosynthesis/geneticsmutationrna,messenger/metabolismsupport,non-uKWDsKWDgov'ttransfectionu937cells/metabolism/KWDvirologyKWDvirusreplication
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Copyright © 1999 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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