HIV infection upregulates caveolin 1 expression to restrict virus production.
Caveolin 1 (Cav-1) is a major protein of a specific membrane lipid raft known as caveolae. Cav-1 interacts with the gp41 of the human immunodeficiency virus (HIV) envelope, but the role of Cav-1 in HIV replication and pathogenesis is not known. In this report, we demonstrate that HIV infection in primary human monocyte-derived macrophages (MDMs), THP-1 macrophages, and U87-CD4 cells results in a dramatic upregulation of Cav-1 expression mediated by HIV Tat. The activity of p53 is essential for Tat-induced Cav-1 expression, as our findings show enhanced phosphorylation of serine residues at amino acid positions 15 and 46 in the presence of Tat with a resulting Cav-1 upregulation. Furthermore, inhibition of p38 mitogen-activated protein kinase (MAPK) blocked phosphorylation of p53 in the presence of Tat. Infection studies of Cav-1-overexpressing cells reveal a significant reduction of HIV production. Taken together, these results suggest that HIV infection enhances the expression of Cav-1, which subsequently causes virus reduction, suggesting that Cav-1 may contribute to persistent infection in macrophages.
Lin
Shanshan
S
Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
Wang
Xiao Mei
XM
Nadeau
Peter E
PE
Mergia
Ayalew
A
D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D051242:Caveolin 1 / Q000096:biosynthesis*; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008264:Macrophages / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014779:Virus Replication; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
C495540:CAV1 protein, human; D051242:Caveolin 1; D016159:Tumor Suppressor Protein p53; D054322:tat Gene Products, Human Immunodeficiency Virus; D048051:p38 Mitogen-Activated Protein Kinases