Reactivation of herpes simplex virus type 2 from a quiescent state by human cytomegalovirus.

Abstract

The ability of human cytomegalovirus to stimulate replication of herpes simplex virus type 2 (HSV-2) was examined. The system used involved HSV-2-infected human embryonic lung cells under conditions (39.5-40°C) in which HSV-2 remains undetectable. Reactivation of HSV-2 was maximal and persisted for the longest duration when cultures were superinfected with 0.02 plaque-forming unit of human cytomegalovirus per cell. Infectious HSV-2 appeared 2 days after superinfection with human cytomegalovirus and ranged from 102 to 106 plaque-forming units per culture. Virus reactivated from these cultures was neutralized by rabbit immune serum produced against HSV-2. The specificity of this interaction was demonstrated by various criteria: production of HSV-2 was not observed in cultures treated with mock infecting fluid, and inactivation of human cytomegalovirus by heat, ultraviolet irradiation, or immune serum prior to superinfection eliminated its ability to induce HSV-2 replication. These results suggest that interaction between these two human herpesviruses may be of importance in herpesvirus latency in vivo.Herpes simplex virus (HSV) is maintained in a latent state (1) within the neural tissue of humans (2-6). The establishment of latency, the state of the virus, and the conditions leading to reactivation of virus are the current foci of research in this area. HSV virions and antigens in latently infected neural tissues were not detected by electron microscopy and immunofluorescence studies (1, 7). Later studies, however, demonstrated the expression of an HSV-specified enzyme, thymidine kinase (8), in the dorsal root ganglia of latently infected mice (9). This evidence suggested that the HSV genome was at least partially expressed during latency. Ganglia from latently infected mice (10) and humans (11) have also been examined by solution hybridization; HSV DNA was detected in neurons during both the acute and latent (or chronic) states (10). In contrast, virus mRNA was not detected during latent infection (10). The lack of detectable HSV mRNA contrasted strongly with the finding of HSV-specified thymidine kinase in the ganglia of latently infected mice. This paradoxical situation was resolved when in situ hybridization methods detected HSV mRNA in a small percentage (0.4-8%) of neurons in human sensory ganglia (11), substantiating that transcription of at least some regions of the HSV genome occurs during latency.We were interested in studying the reactivation of HSV type 2 (HSV-2). Frequently, under natural conditions, the human host is simultaneously a reservoir for multiple animal viruses. The interaction among these harbored viruses may be crucial to the pathological state and may be of particular significance with regard to latent virus infection. Indeed, the replication of numerous viruses has been shown to be affected by the presence of coinfecting viruses such as human adenoviruses and simian virus 40 (12, 13) or simian adenovirus SV15 (14), Marek's disease virus and avian leukosis virus (15), and Molon...

An in vitro Latency System for Herpes Simplex Virus Type 2

“…HCMV was as efficient as HSV-1 ts mutants, in agreement with previous findings in a related in vitro latency system (Colberg-Poley et al, 1979, 1981Wigdahl et al, 1981); the virus produced was identified as HSV-2 by its ability to form plaques on BHK cells, which are non-permissive for HCMV (results not shown). By contrast, adenovirus type 2 (Ad2) or type 5 (Ad5), or tsK which had been irradiated with u.v.…”

Herpes Simplex Virus Type 1 Latency in Rabbit Corneal Cells in Vitro: Reactivation and Recombination Following Intratypic Superinfection of Long Term Cultures

“…human cytomegalovirus (Colberg-Poley et al, 1979. We have selected and isolated HSV genomes lacking XbaI sites normally present (Brown et al, 1984;Harland & Brown, 1985).…”

Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus

“…Reports that ACV in combination with human IFNs produces at least additive inhibitory effects on HCMV replication (17,28) prompted our investigation of the combined use of ACV and IFN-a in plaque reduction and replication kinetic assays. Since ara-A combined with IFNa or BVDU has been shown to act in a synergistic manner to inhibit HSV (16,27) were grown in Dulbecco medium containing 10%o heatinactivated fetal calf serum as previously described (6,7,30). Maintenance medium contained 5% fetal calf serum with supplements as previously described (6,7).…”