title: An infectious murine model for studying the systemic effects of opioids on early HIV pathogenesis in the gut.
abstract: Opioids are known to exacerbate HIV pathogenesis, however current studies have been limited by models of HIV infection. Given that HIV causes many systemic effects via direct infection of host cells as well as indirect bystander effects, it is important to establish a systemic infection model in a small animal so that genetic tools can be utilized to elucidate the mechanisms of action. In this study, the systemic effects of EcoHIV infection, a modified HIV which can infect mouse cells, are examined in conjunction with morphine. EcoHIV infection with opioid treatment induced bacterial translocation from the lumen of the gut into systemic compartments such as liver, which is similar to observations in human patients with LPS. Bacterial translocation corresponds with alterations in gut morphology, disorganization of the tight junction protein occludin, and a concurrent increase in systemic inflammation in both IL-6 and TNFα. Long term infection also had increased expression of inflammatory cytokines in the CNS when co-treated with morphine. Overall, this study shows that EcoHIV is an appropriate model to study the effects of opioids on HIV pathogenesis, including the HIV-induced pathology at early stages of pathogenesis in the gut.
authors.affiliation: Department of Veterinary Population Medicine, University of Minnesota, 1988 Fitch Avenue Room 295, Saint Paul, MN, 55108, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sindberg
authors.forename: Umakant
authors.initials: U
authors.lastname: Sharma
authors.forename: Santanu
authors.initials: S
authors.lastname: Banerjee
authors.forename: Vidhu
authors.initials: V
authors.lastname: Anand
authors.forename: Raini
authors.initials: R
authors.lastname: Dutta
authors.forename: Chao-Jiang
authors.initials: CJ
authors.lastname: Gu
authors.forename: David J
authors.initials: DJ
authors.lastname: Volsky
authors.forename: Sabita
authors.initials: S
authors.lastname: Roy
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000382:microbiology / Q000473:pathology*; D015658:HIV Infections / Q000150:complications / Q000382:microbiology / Q000473:pathology*; D015497:HIV-1; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D062793:Occludin / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D015850:Interleukin-6; D008070:Lipopolysaccharides; D062793:Occludin; D014409:Tumor Necrosis Factor-alpha