Abortive herpes simplex virus infection of nonneuronal cells results in quiescent viral genomes that can reactivate

Abortive viral infections are usually studied in populations of susceptible but nonpermissive cells. Single-cell studies of viral infections have demonstrated that even in susceptible and permissive cell populations, abortive infections can be detected in subpopulations of the infected cells. We have previously identified abortive infections in HeLa cells infected with herpes simplex virus 1 (HSV-1) at high multiplicity of infection (MOI). Here, we tested 4 additional human-derived nonneuronal cell lines (cancerous or immortalized) and found significant subpopulations that remain abortive. To characterize these abortive cells, we recovered cell populations that survived infection with HSV-1 at high MOI. The surviving cells retained proliferative potential and the ability to be reinfected. These recovered cell populations maintained the viral genomes in a quiescent state for at least 5 wk postinfection. Our results indicate that these viral genomes are maintained inside the nucleus, bound to cellular histones and occasionally reactivated to produce new progeny viruses. We conclude that abortive HSV-1 infection is a common feature during infection of nonneuronal cells and results in a latency-like state in the infected cells. Our findings question the longstanding paradigm that alphaherpesviruses can establish spontaneous latency only in neuronal cells and emphasize the stochastic nature of lytic versus latency decision of HSV-1 in nonneuronal cells.