Herpes simplex virus 1 strain 17+ with R2 mutation in UL37 has residual retrograde transport

Abstract

Herpes simplex virus 1 (HSV-1) causes lifelong recurrent infections. Following primary infection of the oral or genital mucosa, HSV-1 travels retrogradely through axons and establishes latency in the cell body of ganglionic neurons of the peripheral nervous system. Periodic reactivation in neurons and anterograde transport of virions back to peripheral regions causes oral or genital ulcerations. Many host and viral factors implicated in retrograde and anterograde transport of HSV-1 have been identified. In particular, studies reported that introducing five amino acid substitutions in the R2 region of the viral tegument protein UL37 was sufficient to completely eliminate retrograde transport of HSV-1 strain F. Here, we introduced the same R2 mutations in the highly neurovirulent HSV-1 strain 17+. We report that this R217 virus has residual retrograde travel. We show that R217 can establish latency in mouse models of ocular and vaginal infection and reactivate. These results contradict published evidence and show that the R2 mutation is not sufficient to fully prevent retrograde transport of HSV-1.