METHAMPHETAMINE AND GENISTEIN MODULATE HERPES SIMPLEX VIRUS TYPE 2 INFECTION AND DISEASE

Frances Valencia^1,2, J.W. Pennock, B.S.², R. Stegall, B.S.², and N. Bourne, Ph.D.^1,2

¹Department of Pathology; ²Sealy Center for Vaccine Development, UTMB

Background: Approximately one in five adults in the United States is seropositive for Herpes simplex virus type 2 (HSV-2). However, little is known about how exogenous factors such as drugs of abuse and dietary supplements alter susceptibility to infection or the course of disease. The psychostimulant methamphetamine (METH) was consumed in the US by over 1.3 million people in 2007 while the phytoestrogen genistein is part of a normal dietary intake. Objective: To examine the impact of METH and genistein on HSV-2 replication in vitro and their ability to alter the course of genital herpes in vivo in an established murine model. Methods: Assessments of the impact of treatment on viral replication were conducted using yield reduction assays. Female C57Bl/6 mice were treated for 5 days with METH (8mg/Kg/day) or saline. All animals had vaginal swab samples collected after challenge to assess viral replication in the genital tract; animals were also examined daily for onset of clinical signs of disease. Results: Genistein significantly reduced HSV-2 replication in yield reduction assays (p=0.01). In studies using the murine model, clinical signs of disease developed more rapidly than did saline treated controls when exposed to a low dose inoculum (mean day of onset 8.3 vs 6.5). Similar results were obtained using a high dose challenge and was associated with significantly increased virus titers in the genital tract of the METH treated animals (p<0.05). Conclusions: These data demonstrate that exogenous substances such as genistein and METH can have a significant impact on viral replication and on the course of genital herpes disease. Thus these results have implications of public health importance. Supported by the Sealy Center for Vaccine Development Predoctoral Fellowship.