HIV-1 Vpr regulates expression of beta chemokines in human primary lymphocytes and macrophages.
The HIV-1 vpr gene encodes a 14-kDa virion-packaged protein that has been implicated in viral pathogenesis. Vpr exhibits profound effects on human primary cells influencing proliferation, differentiation, apoptosis, and cytokine production, in part through NF-kappaB-mediated transcription. NF-kappaB, a potent transcription factor, activates many proinflammatory cytokines/chemokines upon infection. Here, we analyzed the effect of extracellular Vpr as well as the virion-associated Vpr on beta chemokines (MIP-1alpha, MIP-1beta, and RANTES) production in human macrophages and primary lymphocytes (PBLs). Macrophages and PBLs exposed to HIV-1 vpr+ viruses or to recombinant Vpr protein produced significantly less beta chemokines compared with cells infected with HIV-1 vpr-viruses or irrelevant control protein (Gag)-exposed cells. These results suggest that a Vpr-mediated increase in virus replication could be in part through down-regulation of chemokine production.
Muthumani
K
K
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA.
Kudchodkar
S
S
Papasavvas
E
E
Montaner
L J
LJ
Weiner
D B
DB
Ayyavoo
V
V
D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D016336:Gene Products, vpr / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016334:Genes, vpr; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000821:virology; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D011994:Recombinant Proteins / Q000494:pharmacology; D014771:Virion / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology; D054325:vpr Gene Products, Human Immunodeficiency Virus
D019742:Chemokines, CC; D016336:Gene Products, vpr; D011994:Recombinant Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus