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Updated: Jul 14, 2026
A Rat Model of EcoHIV Brain Infection
Published on: January 21, 2021
Expression of the mu opioid receptor in the human immunodeficiency virus type 1 transgenic rat model
Sulie L Chang1, Jose A Beltran, Shilpa Swarup
1Department of Biological Sciences, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA. changsul@shu.edu
Abstract:
Opioids, via the mu opioid receptor (MOR), can exacerbate bacterial infections and the immunopathogenesis of human immunodeficiency virus type 1 (HIV-1) infection. Recently, an HIV-1 transgenic (HIV-1Tg) rat model containing circulating HIV-1 gp120 was created. Using real-time reverse transcription-PCR, we found that MOR mRNA levels were significantly higher in the peritoneal macrophages of the HIV-1Tg rat than those in control animals. Lipopolysaccharide, a bacterial endotoxin, induced secretion of the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-beta (IL-beta), and IL-10 in the HIV-1Tg rat and further increased MOR expression. Ex vivo studies showed that MOR expression was up-regulated in the peritoneal macrophages of F344 control rats by exposure to serum from HIV-1Tg rats and that MOR up-regulation was abolished by addition of gp120 antibody to the serum. In human TPA-differentiated HL-60 cells, which are macrophage-like cells, LPS-induced MOR mRNA up-regulation was greater in gp120-pretreated cells than in vehicle-pretreated cells. Our data suggest that in individuals infected with HIV-1, the MOR is up-regulated, possibly by circulating HIV-1 proteins such as gp120, and HIV-1 proteins may play a significant role in modulating the response to bacterial infection in opioid-using HIV-infected individuals. Furthermore, our results demonstrate that the new HIV-1Tg rat model can be a valuable tool with which to study MOR gene expression and its effects in the continuous presence of HIV viral proteins.
Insights
Opioid receptors (MOR) are upregulated in HIV-1 infection, potentially by HIV proteins like gp120. This may worsen bacterial infections in HIV-positive individuals using opioids.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Opioids exacerbate bacterial infections and HIV-1 immunopathogenesis via mu opioid receptors (MOR).
- An HIV-1 transgenic (HIV-1Tg) rat model expressing HIV-1 gp120 has been developed.
Purpose of the Study:
- To investigate the role of HIV-1 proteins, specifically gp120, in modulating MOR expression in HIV-1 infection.
- To evaluate the utility of the HIV-1Tg rat model for studying MOR gene expression in the context of HIV-1.
Main Methods:
- Real-time reverse transcription-PCR was used to quantify MOR mRNA levels in peritoneal macrophages.
- Lipopolysaccharide (LPS) was used to induce inflammatory responses and assess MOR expression.
- Ex vivo studies exposed macrophages to serum from HIV-1Tg rats and gp120 antibodies.
- Human HL-60 macrophage-like cells were pretreated with gp120 and stimulated with LPS.
Main Results:
- MOR mRNA levels were significantly higher in HIV-1Tg rats compared to controls.
- LPS induced higher levels of inflammatory cytokines (TNF-alpha, IL-1beta, IL-10) and increased MOR expression in HIV-1Tg rats.
- Serum from HIV-1Tg rats upregulated MOR expression in control rat macrophages, an effect blocked by gp120 antibody.
- gp120 pretreatment enhanced LPS-induced MOR mRNA upregulation in HL-60 cells.
Conclusions:
- HIV-1 infection upregulates MOR, potentially mediated by circulating HIV-1 proteins like gp120.
- HIV-1 proteins may significantly influence the response to bacterial infections in opioid-using, HIV-infected individuals.
- The HIV-1Tg rat model is a valuable tool for studying MOR gene expression and its impact during persistent HIV-1 viral protein presence.
