PII-017 - EFFECTS OF HIV AND OPIOIDS ON CHEMOKINE EXPRESSION IN AN INFECTIOUS MOUSE MODEL

E. Miller¹, K. Rademeyer², A. Jones², D. Conway³, K. Hauser¹, M. McRae¹; ¹Virginia Commonwealth University, Richmond, VA, USA, ²Virginia Commonwealth University, Richmond, VA, United States, ³Ohio State University, Columbus, OH, United States.

Background: Even after the advent of antiretroviral therapy, over 40% of people with HIV experience symptoms of HIV-associated neurocognitive disorders (HAND). HIV-induced neuroinflammation is a significant factor in HIV neuropathology and the development of HAND. Concurrent illicit opioid dependence exacerbates HIV neuropathology. Previous studies on illicit opioid-HIV interactions have focused on morphine or heroin. However, illicit opioids increasingly contain fentanyl, which is now present in upwards of 96% of illicit opioids. Fentanyl’s effects on HIV neuropathology are largely unknown. This study compared the effects of fentanyl and morphine on immune signaling via chemokine expression patterns in an infectious HIV mouse model.

Methods: Four-month-old C57BL/6J mice were infected with EcoHIV or mock virus for 15 days and treated with fentanyl (0.05 mg/day), morphine (1.92 mg/day), or saline via osmotic pump for five days. Striatum and hippocampus were collected. A multiplex assay was used to quantify the expression of 13 different chemokines. Chemokine expression patterns were explored using principal component analysis (PCA) and hierarchical clustering analysis (HCA).

Results: PCA revealed chemokine expression patterns within the striatum of fentanyl-treated mice were distinct from morphine and this was driven by higher CCL2, CCL4, CCL5, and CCL11 and lower CCL3 and CXCL10 expression. HCA supported PCA results and illuminated further differences in chemokine expression within fentanyl-treated mice based on EcoHIV status. Fentanyl-treated, EcoHIV+ mice were characterized by higher levels of CCL2, CCL4, CCL5, and CCL11 and lower levels of CCL3 and CXCL10 relative to fentanyl-treated, EcoHIV- mice. In the hippocampus, treatment groups did not cluster distinctively in either PCA or HCA.

Conclusion: Chemokine signatures in fentanyl-treated mice were distinct from morphine-treated mice, and EcoHIV status influenced chemokine signatures within the fentanyl group. The striatum was more vulnerable to inflammatory dysregulation than the hippocampus. Our results indicate fentanyl exposure has the potential to more greatly dysregulate chemokine expression than morphine exposure and may influence chemokine expression differently in the context of HIV.