An Infectious Murine Model for Studying the Systemic Effects of Opioids on Early HIV Pathogenesis in the Gut

• DOI: 10.1007/s11481-014-9574-9
• Publication Date: 2014-12-11T07:53:02Z
• Authors: Gregory M. Sindberg; Umakant Sharma; Santanu Banerjee; Vidhu Anand; Raini Dutta; Chao-Jiang Gu; David J. Volsky; Sabita Roy
• Keywords: Lipopolysaccharides; Male; 0301 basic medicine; Mice, Inbred BALB C; Gastrointestinal Diseases; Interleukin-6; Tumor Necrosis Factor-alpha; HIV Infections; 3. Good health; Analgesics, Opioid; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Liver; Phagocytosis; Bacterial Translocation; Occludin; HIV-1; Animals; Female

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.