Alcohol potentiates HIV-1 infection of human blood mononuclear phagocytes.
BACKGROUND
Acute and chronic alcohol abuse impairs various functions of the immune system and thus has been implicated as a cofactor in HIV infection. The mechanisms by which alcohol affects the function of human immune cells that are the targets for HIV are unknown.


METHODS
Human blood monocyte-derived macrophages (MDM) were incubated with or without alcohol (10-40 mM) for 24 hr and then infected with HIV for 24 hr. Culture supernatants were harvested for HIV reverse transcription assay. HIV entry receptor (CCR5, CD4, and CXCR4) expression was determined by reverse transcription-polymerase chain reaction and flow cytometry assays. Beta-chemokines were analyzed using enzyme-linked immunosorbent assay. Different HIV strains (Bal, SF-162, 89.6, and UG024) were used for infection experiments. In addition, ADA (macrophage-tropic strain) and murine leukemia virus envelope-pseudotyped HIV infection was carried out.


RESULTS
Although alcohol had little effect on HIV T-lymphocyte-tropic strain infection, it significantly enhanced HIV R5 strain infection in MDM. The enhancing effect of alcohol on the HIV R5 strain was further evidenced by the observation that the R5 (ADA) strain envelope-pseudotyped HIV infection is markedly increased by alcohol, whereas murine leukemia virus envelope-pseudotyped HIV infection was not affected. Alcohol significantly up-regulated CCR5 receptor expression and inhibited the endogenous production of beta-chemokines by MDM.


CONCLUSIONS
Alcohol, through the down-regulation of beta-chemokine production and the up-regulation of CCR5 receptor expression, enhances HIV R5 strain infection of MDM and may have an important role as a cofactor in the progression of HIV disease.
Wang
Xu
X
Division of Immunologic and Infectious Disease, Joseph Stokes Jr Research Institute at the Children's Hospital of Philadelphia, Department of Pediatrics, Pennsylvania 19104, USA.
Douglas
Steven D
SD
Metzger
David S
DS
Guo
Chang-Jiang
CJ
Li
Yuan
Y
O'Brien
Charles P
CP
Song
Li
L
Davis-Vogal
Annet
A
Ho
Wen-Zhe
WZ
D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000502:physiology; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D012333:RNA, Messenger / Q000096:biosynthesis
D012333:RNA, Messenger; D000431:Ethanol