TY - JOUR
T1 - An Infectious Murine Model for Studying the Systemic Effects of Opioids on Early HIV Pathogenesis in the Gut
AU - Sindberg, Gregory M.
AU - Sharma, Umakant
AU - Banerjee, Santanu
AU - Anand, Vidhu
AU - Dutta, Raini
AU - Gu, Chao Jiang
AU - Volsky, David J.
AU - Roy, Sabita
N1 - Funding Information:
We would like to thank the support of this work from National Institute for Drug Abuse (NIDA) grant number RO1 DA12104 (SR), RO1 DA022935 (SR), RO1 DA031202 (SR), K05 DA033881 (SR), R01 DA034582 (SR), and RO1 DA017618 (DJV). GS was supported by NIDA supported T32 DA007097.
Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2015/2/20
Y1 - 2015/2/20
N2 - 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.
AB - 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.
KW - Early HIV pathogenesis
KW - EcoHIV
KW - Gastrointestinal (GI)
KW - HIV model
KW - Microbial translocation
KW - Morphine
KW - Opioids
UR - http://www.scopus.com/inward/record.url?scp=84925460927&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925460927&partnerID=8YFLogxK
U2 - 10.1007/s11481-014-9574-9
DO - 10.1007/s11481-014-9574-9
M3 - Article
C2 - 25502600
AN - SCOPUS:84925460927
VL - 10
SP - 74
EP - 87
JO - Journal of NeuroImmune Pharmacology
JF - Journal of NeuroImmune Pharmacology
SN - 1557-1890
IS - 1
ER -