Stephen E. Straus, M.D.

Senior Investigator

Description of Research Program

A team of Ph.D. and M.D. scientists, research nurses, and technical support staff work together to study basic and clinical problems related to the microbial and immunopathogenesis, treatment and prevention of human herpesvirus infections. Over the past 15 years, these scientists accomplished the original cloning and mapping of varicella-zoster virus DNA, developed and applied molecular epidemiologic tools for studying herpesvirus transmission and reactivation, localized and characterized the regulation and function of multiple varicella-zoster virus genes, first discovered the transcripts expressed by herpes simplex and varicella-zoster viruses during their latent infection of human neural tissues, and manipulated herpes simplex virus genes to alter virus reactivation in animal models.

The major current bench research emphases remain the molecular and cellular regulation of herpesvirus latency. The Laboratory of Clinical Infectious Diseases (LCID) has established ocular and genital herpes models in mice and guinea pigs and used these to explore the viral and host factors that regulate herpes simplex virus (HSV) latency and reactivation. In recent studies, we determined that expression of HSV latency transcripts modulate disease reactivation, but the absolute quantity of latent viral DNA in ganglia is the major determinant of reactivation rates. We are using mice deleted for expression of various cytokines to explore immune regulation of latency and reactivation. Most recently, we have created a mouse transgenic for HSV latency-associated transcripts. Ongoing studies are also exploiting animal models to test the efficacy of antiviral drugs, immunoglobulin, and novel DNA-based vaccines on HSV latency and reactivation.

A variety of clinical studies that complement these laboratory investigations are being undertaken. Among the accomplishments of such studies was the development of acyclovir for suppression of recurrent genital and oral herpes, demonstration of asymptomatic virus shedding in infected men and women, and completion of the first human trials of recombinant glycoprotein vaccines for genital herpes. Additional studies examine the ability of antiviral drugs to prevent transmission of genital herpes.

Memberships

• American Society for Clinical Investigation
• Association of American Physicians
• Infectious Diseases Society of America

Editorial Boards

• Fields Virology
• The Journal of Virology
• Virology
• The Journal of Neurovirology
• The Journal of Human Virology
• Antimicrobial Agents and Chemotherapy

Research Group Members

Richard Williams, Kening Wang, Rona LeBlanc, Dong-Xiang Xia, Adriana Marques, Sarat Dalai, Erik Mont, Janet Dale, and Patricia Hohman.

Selected Recent Publications

Lekstrom-Himes JA, Hohman P, Warren T, Wald A, Nam JM, Simonis T, Corey L, Straus SE. Association of major histocompatibility complex determinants with development of symptomatic and asymptomatic genital Herpes Simplex Virus Type 2 Infections. Journal of Infectious Diseases. 1999. 179: 1077-1085.

Lekstrom-Himes JA, Pesnicak L, Straus SE. The quantity of latent viral DNA correlates with the relative rates at which Herpes Simplex Virus Types 1 and 2 cause recurrent genital herpes outbreaks. Journal of Virology. 1998. 72: 2760-2764.

Wang K, Pesnicak L,  Straus SE. Mutations at the 5’-end of the HSV-2 LAT promoter affect LAT expression in vivo but not the rate of spontaneous reactivation of genital herpes. Journal of Virology. 1997. 71: 7903-7910.

Williams RK, Straus SE. Specificity and affinity of binding of herpes simplex virus type 2 glycoprotein B to glycosoaminoglycans. Journal of Virology. 1997. 71: 1375-1380.

Lekstrom-Himes JA, Pesnicak L, Straus SE. The quantity of latent viral DNA correlates with the relative rates at which Herpes Simplex Virus Types 1 and 2 cause recurrent genital herpes outbreaks. Journal of Virology. 1998. 72: 2760-2764.

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