385 Morphine Enhances HIV Infection of Human Blood Mononuclear Phagocytes through Modulation of beta-Chemokines and CCR5 Receptor C. J. Guo*, Y. Li, S. Tian, X. Wang, S. D. Douglas, W. Z. Ho Children's Hosp of Philadelphia, PA
Background: Injection drug use (IDU) remains a significant risk for acquiring human immunodeficiency virus (HIV) infection. Although it is known that opiates such as morphine suppresses immune system and promotes HIV infection in vitro, the mechanisms by which morphine enhances HIV infection of human immune cells remain largely unknown.
Methods: Human blood monocyte-derived macrophages (MDM) were infected with R5, X4, and R5X4 HIV strains. HIV replication was determined by reverse transcriptase activity assay. HIV receptor expression (CD4, CXCR4, and CCR5) were determined by RT-PCR and flow cytometry assays. beta-chemokine production was analyzed by ELISA. In addition, HIV R5 strain (ADA) and murine leukemia virus (MLV) envelope-pseudotyped HIV infection was performed to determine whether morphine affects HIV infection of macrophages at entry level.
Results: Morphine significantly enhanced HIV R5 strain infection of MDM, while it had little effect on X4 strain infection. The R5 strain (ADA) envelope-pseudotyped HIV infection was markedly increased by morphine, while murine leukemia virus envelope-pseudotyped HIV infection was not significantly affected. Furthermore, morphine significantly up-regulated CCR5 receptor expression and inhibited the endogenous production of beta-chemokines in MDM. The opioid receptor antagonist, naltrexone, blocked the effects of morphine on beta-chemokine production.
Conclusions: Opioids most likely through down-regulation of beta-chemokine production and up-regulation of CCR5 receptor expression enhance HIV R5 strain infection of macrophages. Opioids may play an important role as a positive co-factor in the immunopathogenesis of HIV infection.