Description:

Department of Microbiology-Immunology Seminar Series

Patricia A. Spear Research Colloquium in Virology

"Origins and impacts of Sequence Diversity in Herpes Simplex Virus (HSV) Infections”

Moriah Szpara, PhD / Pennsylvania State University

Description:

Herpes simplex virus 1 (HSV-1) and HSV-2 cause millions of chronic infections. These viruses cause epithelial oral “cold” sores and genital lesions, which recur lifelong due to reactivation from a latent viral reservoir in neurons. Clinical outcomes from HSV infection are highly diverse, ranging from surface lesions, to asymptomatic shedding, to severe and potentially lethal encephalitis. This variation is thought to be caused by a combination of factors, including viral genetic differences, human genetic predisposition, and environmental variables. Recent comparative genomics studies of HSV-1, from our lab and others, have demonstrated that isolates from independent human hosts can differ in 2-4% of the viral genome. The impacts of naturally occurring viral genetic variations on virulence and pathogenesis in humans are unknown, but data from animal models raise the intriguing possibility that viral genetic differences may contribute to differences in disease outcomes. We are leveraging our expertise in genomics and bioinformatics to compare viral isolates from diverse human clinical settings, to discover how viral genetic differences correlate with distinct disease outcomes. In addition to genomics, we employ cell-based assays, animal models, molecular and biochemical approaches, and data derived from human clinical studies. If these in vitro data can be linked to human outcomes in the future, the ability to gauge potential virulence from viral genotype would provide a powerful tool for future diagnostics and prediction of clinical outcomes. These studies build on related research examining other viral, bacterial and parasite pathogens that likewise harbor genetic diversity and elicit a range of clinical outcomes.