Recurrent Genital Infection in the Guinea Pig: Differences between Herpes Simplex Types 1 and 2

Abstract

Recurrence rates of genital infections are significantly higher for heφes simplex virus (HSV) type 2 than HSV type 1. Reasons for this difference are not known. In this report, multiple strains of HSV-1 and HSV-2 were evaluated in the guinea-pig model. HSV-2 strains showed significantly higher genital lesion recurrence than HSV-1, including HSV-1 McKrae strain which is highly recurrent in ocular infections. HSV-2 strains were also associated with more frequent asymptomatic vaginal virus shedding. Further study showed that HSV-1 strains replicated as well as HSV-2 in both the genital tract and the nervous system during acute infection. In addition, no difference was detected between HSV-1 and HSV-2 in nervous system latency. Thus, a number of possible explanations for the observed difference in genital heφes recurrence rates were examined and excluded.

Superior Efficacy of Helicase-Primase Inhibitor BAY 57–1293 for Herpes Infection and Latency in the Guinea Pig Model of Human Genital Herpes Disease

“…The loss of HSV DNA in the ganglia was suggested to be a consequence of the destruction of latently-infected neurons following reactivation. This finding would explain why the number and severity of recurrent episodes in intravaginally infected guinea pigs decline over time (Landry et al, 1992;Stanberry et al, 1985). In most patients, recurrence rates and severity also decrease after 1 year (Benedetti et al, 1999).…”

“…After infection with HSV-2, genital herpes disease developed in untreated guinea pigs as described previously (Landry et al, 1992;Lukas et al, 1974;Stanberry et al, 1982;Stanberry et al, 1985;Stanberry, 1994). Vesicles first appeared on the external genitalia 3-4 days p.i.…”

Pathogenesis of Herpes Simplex Virus Type 2 Virion Host Shutoff (vhs) Mutants

“…HSV-2 primarily causes genital infections but is also capable of necrotizing stromal keratitis, encephalitis, meningitis, and neonatal ophthalmic, and neurologic complications in infants surviving infection (27,32). In animal models, HSV-2 is significantly more neurovirulent than HSV-1 by all routes of infection (12,16,26).HSV-1 mutants lacking vhs function have a significantly reduced capacity to replicate in the cornea, trigeminal ganglia, and brains of mice and show impaired establishment and reactivation from latency in a murine eye model of latency and pathogenesis (29-31). UL41 mutant viruses, however, remain highly immunogenic, suggesting that deletion of vhs may be a useful property for live-attenuated herpesvirus vaccines (10,34,35).…”

“…HSV-2 primarily causes genital infections but is also capable of necrotizing stromal keratitis, encephalitis, meningitis, and neonatal ophthalmic, and neurologic complications in infants surviving infection (27,32). In animal models, HSV-2 is significantly more neurovirulent than HSV-1 by all routes of infection (12,16,26).…”

Herpes Simplex Infection

“…Recurrent infections seem to be precipitated by exposure to sunlight, wind, local trauma, and emotional stress. Oral HSV-1 re-infections develop in 20% to 50% of the population, whereas oral HSV-2 reoccurs at a 5% rate (Landry, Myerson, & Dull, 1992). This may be related to the ability of the two types of HSV to establish latency in either the sacral or trigeminal ganglia and to differences in growth and reproductive patterns (Su, Wu, & Lin, 1995;Lekstrom-Himes, et al, 1998).…”