Effect of Pyran on Latency After Herpes Simplex Virus Infections

Abstract

The immunomodulator pyran protected mice against both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections. In infections of the lip with HSV-1, prophylactic administration of pyran reduced the severity of the herpetic lesions and enhanced their resolution, but did not decrease the high incidence of development of latent HSV-1 infection of the trigeminal ganglia. In vaginal infections with HSV-2, prophylactic administration of pyran either systemically or locally reduced mortality, reduced the incidence of mice with vaginal HSV-2 infection, and did not alter the low incidence of latent infection of the spinal dorsal root ganglia. Pyran treatinent before systemic herpetic infection after intravenous inoculation of HSV-2 also reduced mortality and virus replication, as evidenced by a decreased antibody response in the survivors, and it either reduced latent infection in the spinal dorsal root ganglia or did not predispose mice to latent infection. Treatment with the immunomodulator appeared to inhibit or reduce HSV infection early in viral pathogenesis in all three model systems, producing protection from clinical disease and resulting in less virus to induce a systemic antibody response, with either a reduction in latent virus infection or no enhancement of development of latency. In all of the HSV models, the development of latent herpetic infection was closely correlated with sufficient virus replication early in the infection to induce a systemic neutralizing-antibody response.

Immune responses to labial infection of BALB/c mice with herpes simplex virus type 1

“…Considerable interest has recently been directed toward animal models of this infection which attempt to establish efficacy of antiviral treatments (15,20,21) and immunization procedures (7,23). We have demonstrated that infection ofthe lip with HSV-1 reproducibly causes the typical herpetic mucocutaneous lesion that can be monitored clinically and virologically (7,15). Similar to the human disease, there is limited mortality, and in the majority of mice the virus establishes latent infection in the trigeminal ganglion, which is readily accessible for determination of latent virus.…”

“…These provide a basis for defining changes in the infectious process and immune responses that occur in immunized animals (7) or in animals treated with antiviral drugs or immunomodulators (15).…”

Heparin, Heparinoids, Synthetic Polyanions, and Anionic Dyes

“…When an ineffective hoof and mouth vaccine was given intraperitoneally simultaneously with pyran it resulted in 100% protection of mice; other work has shown anti-viral action even without vaccine adjuvancy: Morahan et al (46) demonstrated that pyran could protect mice in-vivo from herpes type 1 and type 2 (HSV) infection with reduction of both mortality and the severity of lesions. This use of IV pyran post herpes infection reduced virus titers and resultant pathogenesis suggesting that it may have value in early or latent herpes infection.…”

Alphaherpesvirus DNA replication in dissociated human trigeminal ganglia

“…The ability to model HSV-1 latency in mice (Morahan et al 1979) and rabbits (Shimomura et al 1983) has greatly advanced the understanding of virus reactivation (Webre et al 2012). However, VZV is a uniquely human virus and the lack of an animal model has hindered insight into its reactivation (Shahzad et al 2015).…”