Sequence variability in UL39 and UL53 genes of Herpes simplex virus 1 may contribute to neurovirulence

Abstract

Herpes simplex virus 1 (HSV-1) is a neuroinvasive human pathogen that evades host immune responses and results in life-long infection. Primary infections generally occur around the mouth and lips from viral transmission though oral secretions. Following infection, HSV-1 spreads to the host nervous system and establishes latency. The virus’s ability to reactivate infection depends on the site of infection, virus strain, and host immunity. HSV-1 infection normally causes mild symptoms; however, in rare cases the virus enters the central nervous system and, if untreated, can lead to fatal encephalitis. The purpose of this study was to explore genetic variation in HSV-1 and consider how frequently differences that may contribute to central nervous system virulence occur in circulating viral strains.Twenty-two HSV strains were obtained from collaborators at the Centers for Disease Control and Prevention. These strains vary in their neurovirulence as determined previously in mouse studies. Here, we assessed variation in the DNA sequences of two viral genes designated UL39 and UL53 (encoding ribonucleotide reductase and glycoprotein K, respectively) due to their involvement in HSV-1 neurovirulence. Sequences of these genes from the twenty-two viral strains were compared to identify variations that correlate with high or low neurovirulence.