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Morphine reduces mortality in mice following ocular infection with HSV-1
1Louisiana State University Medical Center, Department of Pharmacology, Microbiology, Immunology and Parasitology, New Orleans 70112-1393, USA.
Abstract:
To determine the effect of chronic opioid treatment on mice infected with herpes simplex virus (HSV-1), female ICR mice were administered saline or morphine (25 mg/kg) subcutaneously (s.c.) 3 X /day and infected five days later via corneal scarification and inoculation with 150-210 plaque forming units of HSV-1. Mice deprived of morphine succumbed following infection faster than morphine- or saline-maintained mice, and morphine-maintained mice had a higher cumulative survival than either saline-maintained or morphine-deprived mice. There was no significant difference in cytokine mRNA or protein levels by RT-PCR and ELISA, respectively, in the eyes, trigeminal ganglia, cerebellum, or brain stem, comparing morphine-maintained to saline-treated mice. Similarly, there were no differences in the viral load in the eyes and trigeminal ganglia during the acute infection comparing these two groups assayed three and six days post-infection. While there were no differences in the expression of viral transcripts in the eyes and trigeminal ganglia during the acute infection, HSV-1 infected cell polypeptide 27 expression was reduced in the brain stem of morphine-maintained mice. Collectively, the results suggest that mice maintained on morphine antagonize the spread of HSV-1 in the central nervous system and thus, reduce the incidence of viral-induced encephalitis.
Insights
Chronic opioid treatment with morphine in mice reduced herpes simplex virus type 1 (HSV-1) spread in the central nervous system, decreasing the incidence of viral encephalitis and improving survival rates.
Area of Science:
- Neurovirology
- Immunopharmacology
Background:
- Opioid use is common, and herpes simplex virus type 1 (HSV-1) can cause serious neurological complications.
- The impact of chronic opioid administration on HSV-1 infection and subsequent encephalitis is not well understood.
Purpose of the Study:
- To investigate the effects of chronic morphine treatment on HSV-1 infection and encephalitis in a mouse model.
- To determine if morphine influences viral load, host immune response, or neurological spread of HSV-1.
Main Methods:
- Female ICR mice received daily subcutaneous injections of morphine or saline for five days prior to corneal inoculation with HSV-1.
- Viral load, cytokine expression, and viral transcript levels were assessed in various tissues (eyes, trigeminal ganglia, brain stem, cerebellum) at different time points post-infection.
- Survival rates were monitored.
Main Results:
- Morphine-maintained mice exhibited higher cumulative survival rates compared to saline-treated or morphine-deprived mice.
- No significant differences in viral load or cytokine expression were observed between morphine-maintained and saline-treated groups during acute infection.
- Reduced expression of HSV-1 infected cell polypeptide 27 was noted in the brain stem of morphine-maintained mice, suggesting attenuated viral spread in the CNS.
Conclusions:
- Chronic morphine administration appears to antagonize HSV-1 central nervous system spread in mice.
- Morphine treatment may reduce the incidence of HSV-1-induced encephalitis, potentially through mechanisms independent of acute immune responses or viral replication in peripheral tissues.