Published online before print May 5, 2008

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Copyright © 2008 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2008.070971

Accepted for publication February 22, 2008.

Article

Methamphetamine Enhances HIV Infection of Macrophages

Hao Liang^*, Xu Wang^*, Hui Chen^*, Li Song^*, Li Ye^*, Shi-Hong Wang^*, Yan-Jian Wang^*, Lin Zhou^*¶, and Wen-Zhe Ho^*@

From the Division of Allergy and Immunology,* Joseph Stokes, Jr., Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; the Center for AIDS Research and Department of Epidemiology of School of Public Health, and the First Affiliated Hospital, Guangxi Medical University, Nanning City, People's Republic of China; and the Renmin Hospital of Wuhan University, and Tongji Medical College,^¶ Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China

^@ To whom correspondence should be addressed. E-mail: ho{at}email.chop.edu.

	Abstract

Epidemiological studies have demonstrated that the use of methamphetamine (meth), a sympathomimetic stimulant, is particularly common among patients infected with HIV. However, there is a lack of direct evidence that meth promotes HIV infection of target cells. This study examined whether meth is able to enhance HIV infection of macrophages, the primary target site for the virus. Meth treatment resulted in a significant and dose-dependent increase of HIV reverse transcriptase activity in human blood monocyte-derived macrophages. Dopamine D1 receptor antagonists (SCH23390 and SKF83566) blocked this meth-mediated increase in the HIV infectivity of macrophages. Investigation of the underlying mechanisms of meth action showed that meth up-regulated the expression of the HIV entry co-receptor CCR5 on macrophages. Additionally, meth inhibited the expression of endogenous interferon- and signal transducer and activator of transcription-1 in macrophages. These findings provide direct in vitro evidence to support the possibility that meth may function as a cofactor in the immunopathogenesis of HIV infection and may lead to the future development of innate immunity-based intervention for meth users with HIV infection.

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