Influence of methamphetamine on genital herpes simplex virus type 2 infection in a mouse model

Background: Use of the stimulant methamphetamine (METH) is increasingly common, with >35 million users worldwide. There is a known association between stimulant use and an increased incidence of HIV and other sexually transmitted infections (STIs). METH is known to have immune modulatory properties. However, the impact of METH on normal immune responses and disease pathogenesis with STIs has not been fully examined. Methods: We used a well-characterized murine model to investigate the impact of METH use on genital herpes simplex virus type 2 infection. Plaque assay and quantitative real-time polymerase chain reaction were used to measure viral replication. Cytokine bead array and enzyme-linked immunosorbent assay were used to determine levels of cytokines during host innate immune response. Results: METH treatment altered behavior, onset of clinical signs, and disease progression. METH-treated mice also had a thinned vaginal epithelium and an increase in virus present in the sensory ganglia. In addition, METH produced a local dysregulation of cytokine secretion that contrasts with its minimal impact on systemic cytokine secretion. Conclusions: Results suggest that the METH alterations of the host immune response partially contribute to enhanced genital herpes disease progression. These findings will improve understanding of METH use on host immune responses and susceptibility to disease.