Key result
HSV-1 strain 17+ UL37 R2 mutation retains retrograde transport and establishes latency in mice.
Why the study?
Studies reported that five amino acid substitutions in the R2 region of UL37 eliminated retrograde transport in HSV-1 strain F, prompting investigation of the same mutations in the neurovirulent strain 17+.
The R2 mutation in UL37 is not sufficient to fully prevent retrograde transport of HSV-1 strain 17+, challenging previous findings in strain F.
R2 mutation fails to fully block HSV-1 retrograde transport in mice; challenges prior strain F reports and leaves open UL37 latency mechanisms.
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 R2 17 virus has residual retrograde travel. We show that R2 17 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.
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Walter et al. (2025) studied HSV-1 infection (n=55). HSV-1 strain 17+ with R2 mutation in UL37 (R217) vs. Unvaccinated mice / wild-type HSV-1 was evaluated on Establishment of latency in ganglia (trigeminal and dorsal root ganglia) and viral shedding upon reactivation. HSV-1 strain 17+ with the R2 mutation in UL37 demonstrated residual retrograde transport and established latency in mouse models of ocular and vaginal infection, contradicting previous reports.
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