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

Herpes simplex virus 1 (HSV-1) is a ubiquitous pathogen without a cure or vaccine. HSV-1 travels through nerves between the oral and genital mucosa and the peripheral nervous system, where it establishes lifelong latency. Studies reported that introducing five amino acid substitutions in the R2 region of the viral tegument protein UL37 was sufficient to completely eliminate the retrograde transport of HSV-1 strain F from the mucosa to the nervous system. Here, we present contradictory findings. We report that an HSV-1 virus from strain 17+ with the same R2 mutation has residual retrograde transport. This shows that the R2 mutation is not sufficient to fully prevent the retrograde transport of HSV-1 in all settings. This finding may be particularly relevant for assessing the safety of prospective live-attenuated vaccines that include the R2 mutation.