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Published on: August 15, 2012
Alcohol potentiates HIV-1 infection of human blood mononuclear phagocytes
Xu Wang1, Steven D Douglas, David S Metzger
1Division of Immunologic and Infectious Disease, Joseph Stokes Jr Research Institute at the Children's Hospital of Philadelphia, Department of Pediatrics, Pennsylvania 19104, USA.
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.
Conclusion:
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.
Insights
Alcohol consumption enhances HIV R5 strain infection in macrophages by increasing CCR5 receptor expression and reducing beta-chemokines. This suggests alcohol may worsen HIV disease progression.
Area of Science:
- Immunology
- Virology
- Addiction Medicine
Background:
- Alcohol abuse impairs immune function, potentially co-infecting with HIV.
- Mechanisms of alcohol's effect on HIV target cells remain unclear.
Purpose of the Study:
- To investigate how alcohol affects human immune cells targeted by HIV.
- To elucidate the role of alcohol in HIV infection and disease progression.
Main Methods:
- Monocyte-derived macrophages (MDM) were exposed to alcohol and then infected with HIV.
- HIV entry receptor expression (CCR5, CD4, CXCR4) was analyzed.
- Beta-chemokine production was measured, and various HIV strains were used for infection.
Main Results:
- Alcohol significantly enhanced HIV R5 strain infection in MDM.
- Alcohol up-regulated CCR5 receptor expression and inhibited beta-chemokine production.
- T-lymphocyte-tropic HIV strains were less affected by alcohol.
Conclusions:
- Alcohol enhances HIV R5 strain infection by up-regulating CCR5 and down-regulating beta-chemokines.
- Alcohol may act as a cofactor in HIV disease progression.
- Understanding these mechanisms is crucial for managing co-infections.
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