Methadone enhances human influenza A virus replication.
Growing evidence has indicated that opioids enhance replication of human immunodeficiency virus and hepatitis C virus in target cells. However, it is unknown whether opioids can enhance replication of other clinically important viral pathogens. In this study, the interaction of opioid agonists and human influenza A/WSN/33 (H1N1) virus was examined in human lung epithelial A549 cells. Cells were exposed to morphine, methadone or buprenorphine followed by human H1N1 viral infection. Exposure to methadone differentially enhanced viral propagation, consistent with an increase in virus adsorption, susceptibility to virus infection and viral protein synthesis. In contrast, morphine or buprenorphine did not alter H1N1 replication. Because A549 cells do not express opioid receptors, methadone-enhanced H1N1 replication in human lung cells may not be mediated through these receptors. The interaction of methadone and H1N1 virus was also examined in adult mice. Treatment with methadone significantly increased H1N1 viral replication in lungs. Our data suggest that use of methadone facilitates influenza A viral infection in lungs and might raise concerns regarding the possible consequence of an increased risk of serious influenza A virus infection in people who receive treatment in methadone maintenance programs.
Center for Neuropsychiatric Research, National Health Research Institutes, Taiwan.|Department of Life Science, Fu Jen Catholic University, Taiwan.
Yun-Hsiang
YH
Chen
Center for Neuropsychiatric Research, National Health Research Institutes, Taiwan.
Kuang-Lun
KL
Wu
Center for Neuropsychiatric Research, National Health Research Institutes, Taiwan.
Ming-Ta
MT
Tsai
Department of Occupational Therapy, Fu Jen Catholic University, Taiwan.
Wei-Hsien
WH
Chien
Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan.
Mao-Liang
ML
Chen
Center for Neuropsychiatric Research, National Health Research Institutes, Taiwan.
Yun
Y
Wang
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D018929:Cell Culture Techniques; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008691:Methadone / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D014779:Virus Replication / Q000502:physiology*
D000701:Analgesics, Opioid; D008691:Methadone
buprenorphine; cytokine; influenza virus; methadone; morphine