Treatment of Experimental Herpesvirus Infections with Phosphonoformate and Some Comparisons with Phosphonoacetate

Abstract

Phosphonoformate (PF) at a concentration of 5 to 10 μg/ml inhibited the growth of type 1 strains of herpes simplex virus (HSV) in tissue culture, whereas 20 to 30 μg/ml was required for inhibition of type 2 strains and about 50 μg/ml was required for murine cytomegalovirus. In mice inoculated intraperitoneally or intracerebrally with HSV or intraperitoneally with murine cytomegalovirus, treatment with 250 to 400 mg of PF per kg twice daily for 5 days had only minimal effectiveness. When mice were inoculated intravaginally (i.vg.) with HSV type 2 and treated i.vg. with 10% PF beginning 3 h after viral inoculation, treatment was effective in completely inhibiting viral replication in the genital tract. If i.vg. therapy was initiated 24 h after infection, when the mice had a mean virus titer of 10 5 plaque-forming units in vaginal secretions, a significant reduction in the mean virus titer was observed on days 3, 5, and 7 after infection as compared with control animals. In guinea pigs treated i.vg. with 10% PF beginning 6 h after i.vg. inoculation with HSV type 2 there was also complete inhibition of viral replication in the genital tract, and no extenal lesions developed. When therapy was initiated 24 h after infection there was a 4 to 5-log decrease in viral titers on days 3, 5, and 7 of the infection and a slight delay in the development of external lesions.

Treatment of experimental herpes simplex virus encephalitis with (E)-5-(2-bromovinyl)-2'-deoxyuridine in mice

“…(19,24). Other antiherpes drugs, such as 5-iodo-2'-deoxyuridine (18,19,23,26), 1-p-D-arabinofuranosylcytosine (15,19), 1 -,-D-ribofuranosyl-1 ,2 ,4-triazole-3-carboxamide (Virazole, ribavirin) (25), and phosphonoformate (17), have proven to be ineffective in the systemic treatment of HSV encephalitis. Two other compounds, 5-trifluoromethyl-2'-deoxyuridine (6) and 5-ethyl-2'-deoxyuridine (7), have been reported to alter the course of HSV encephalitis.…”

Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models

“…Following virus inoculation, the animals were weighed and monitored daily for evidence of primary disease. Virus-induced lesions were scored by a single investigator for 15 days after inoculation, using a method described previously (13). In brief, primary genital skin disease was quantified by use of a lesion score scale as follows: 0, no disease; 1, redness or swelling of external vagina; 2, a few small vesicles; 3, several large vesicles; and 4, several large ulcers with maceration.…”

Clinical and Serological Outcome of Genital Herpes Simplex Virus (HSV) Type 2 Inoculation following Oral HSV Type 1 Infection in Guinea-pigs

“…Samples were frozen at -70 °C until virus was titrated by plaque assay in rabbit kidney cells (Bernstein et al, 1986). To compare the differences in mean viral titres we computed the area under the log10 virus titre-day curve (viral shedding curve) (Kern et al, 1978).…”