Recurrent vaginal shedding of herpes simplex type 2 virus in the mouse and effects of antiviral therapy

Abstract

A mouse model of recurrent herpes simplex type 2 (HSV-2) would improve our understanding of the immunobiology of recurrent disease and provide a useful model for evaluating antiviral treatments. We developed a model to evaluate recurrent vaginal HSV-2 shedding using high dose Acyclovir (ACV) therapy begun at 3 days post infection (dpi). Treatment with 150 mg/kg of ACV for 10 days increased survival to 80% following vaginal challenge with HSV-2 strain 186 and to 100% after challenge with strain MS. We then evaluated recurrent vaginal HSV-2 shedding in surviving mice. Although infectious virus was not detected in vaginal samples after 21 dpi, viral DNA was detectable by PCR in 80% of mice (47/59) on at least one day, while no animal was positive for virus on every day. ACV therapy administered from day 21-31 significantly reduced recurrent virus shedding during this period from 7.3% (8/109 swabs) to 0.8% (1/126 swabs) (P=0.013). Lastly, ACV-rescued HSV-2 infected mice treated with cyclophosphamide at 35 and 38 dpi rapidly succumbed, indicating that this model can be used to study immune control of the persistent infection. Thus, this model provides an inexpensive model for evaluating therapeutic strategies and immune control of persistent HSV.

A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

“…Sacral nerves and genital ganglia were protease digested, and DNA was extracted as described above. Molecular analysis was carried out by using an HSV-2-specific nested PCR as described previously (16,21). The first and second PCR primer pairs were 6AF (5=-TC AGCCCATCCTCCTTCGGCAGTA-3=)/6BR (5=-GATCTGGTACTCGA ATGTCTCCG-3=) and 6CF (5=-AGACGTGCGGGTCGTACACG-3=)/ 6DR (5=-CGCGCGGTCCCAGATCGGCA-3=), respectively.…”

Proteomic Characterization of Acyclovir-Induced Nephrotoxicity in a Mouse Model

“…In total, 30 ICR mice were purchased from the Zhejiang Experimental Animal Center, China and randomly divided into three groups (n = 10 per group) to receive saline, 150 mg/kg ACV [2] , [10] , or 600 mg/kg ACV once-daily for 9 days. Mice were kept at room temperature (18–24°C) and 70±10% humidity, with a light-dark cycle (12 h–12 h).…”