Ganglionic Herpes Simplex and Systemic Acyclovir

Pavan-Langston, Deborah; Park, No Hee; Hettinger, Michael E.

doi:10.1001/archopht.1981.03930020291019

Archives of Ophthalmology

1981

DOI: 10.1001/archopht.1981.03930020291019

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Ganglionic Herpes Simplex and Systemic Acyclovir

Deborah Pavan-Langston¹,

No Hee Park²,

Michael E. Hettinger³

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1982

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Cited by 21 publications

(12 citation statements)

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“…At present, antiviral chemotherapy is generally recognized as the most promising way to eliminate or control latent herpes simplex virus (HSV) infection of ganglia. Unfortunately, although the prophylactic administration of the available drugs can prevent the establishment of latent HSV infection, there is no drug that has any effect on already established latent HSV infection (2,7,10,11,13). The efficacy of acyclovir (ACV) in preventing the in vitro reactivation of latent HSV has already been confirmed (6,7,9), but so far nothing has been reported about the effectiveness of 2,2'-O-cyclocytidine (CC), which has been used in the People's Republic of China for the treatment of HSV ocular diseases for more than 10 years and which has an antiviral effect that has been confirmed in different types of HSV keratitis (3).…”

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confidence: 99%

“…The scarified eyes of mice were inoculated with a 10-,ul suspension of HSV-1 (103 5 TCID50/ml, i.e., 10 times the 50% lethal dose), as described previously (10).…”

mentioning

confidence: 99%

“…The generally accepted explanation is that the reactivation of all latent HSV-1 is not a simultaneous process in vitro (10). This could leave at least part of the total viral reservoir to serve as the source for future infectious virus once the drug is removed from the medium.…”

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confidence: 99%

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Effects of 2,2'-O-cyclocytidine and acyclovir on latent herpes simplex virus in trigeminal ganglia of mice

Liu¹,

Chen²,

Song³

et al. 1986

Antimicrob Agents Chemother

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The effects of 2,2'-O-cyclocytidine (CC) and acyclovir (ACV) on latent herpes simplex virus (HSV) in trigeminal ganglia were studied in an in vitro model using reactivation of HSV type 1 (HSV-1) as a model. It was shown that both CC (10 ,ug/ml) and ACV (2.5 ,ug/ml) significantly inhibited the reactivation of the latent HSV-1 in infected ganglia. The effect of CC (25 jLg/ml), which was as good as that of ACV (10 ,ug/ml), did not last as long as that of ACV after removal of the drugs. The latent state of HSV-1 in vitro was dependent on the continuous presence of either drug. Even though the latent HSV-1 could not be eliminated completely from the trigeminal ganglia by discontinuous administration of either drug, its titers were markedly reduced. The combination of CC and ACV had a synergistic effect on preventing the reactivation of the latent HSV-1 in vitro.Latently infected ganglia have been thought to be the source of virus for recurrent herpetic diseases in humans (8). At present, antiviral chemotherapy is generally recognized as the most promising way to eliminate or control latent herpes simplex virus (HSV) infection of ganglia. Unfortunately, although the prophylactic administration of the available drugs can prevent the establishment of latent HSV infection, there is no drug that has any effect on already established latent HSV infection (2,7,10,11,13). The efficacy of acyclovir (ACV) in preventing the in vitro reactivation of latent HSV has already been confirmed (6, 7, 9), but so far nothing has been reported about the effectiveness of 2,2'-O-cyclocytidine (CC), which has been used in the People's Republic of China for the treatment of HSV ocular diseases for more than 10 years and which has an antiviral effect that has been confirmed in different types of HSV keratitis (3). In this study we investigated the effects of CC and ACV on latent HSV infection in trigeminal ganglia (TG) in combination or singly, and made a preliminary exploration of the possibility of eliminating or controlling latent HSV infection by discontinuous treatment with CC and ACV.MATERIALS AND METHODS Virus. HSV type 1 (HSV-1) strain SM44 was obtained from the Institute of Virology, China National Centre for Preventive Medicine, and was propagated on African green monkey kidney cells (Vero cells) to yield a titer of 106.5 50% tissue culture infective doses (TCID50) per milliliter. Eagle's minimal essential medium was used.Mice. Inbred strain 615 mice (age, 5 weeks; weight, 15 to 18 g) were maintained for at least 1 week before the experiment.Drugs. CC and 9-(2-hydroxyethoxymethyl)guanine (ACV) used in this study were supplied by the Shanghai No. 12 Pharmaceutical Factory and the Hubei Institute of Medicine Industry, respectively. One percent of CC solution and ACV suspension were prepared and stored at -10°C until used.Inoculation of HSV-1. The scarified eyes of mice were inoculated with a 10-,ul suspension of HSV-1 (103 5 TCID50/ml, i.e., 10 times the 50% lethal dose), as described previously (10).Determination of virus titer in TG...

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mentioning

confidence: 99%

“…The scarified eyes of mice were inoculated with a 10-,ul suspension of HSV-1 (103 5 TCID50/ml, i.e., 10 times the 50% lethal dose), as described previously (10).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effects of 2,2'-O-cyclocytidine and acyclovir on latent herpes simplex virus in trigeminal ganglia of mice

Liu¹,

Chen²,

Song³

et al. 1986

Antimicrob Agents Chemother

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“…The results showed that the extent of colonization of ganglia by virus is related to the time elapsed between virus inoculation and application of this agent. In most cases, treatment started up to 12 h after inoculation prevented invasion of ganglia by virus HSV (4, 6, 7,13,15,17). Compounds such as arabinosyl adenine or arabinosyl adenine monophosphate are ineffective on comparably early application (5).…”

mentioning

confidence: 99%

“…), and quantitative data have been obtained regarding the progress of virus accumulation in sensory ganglia during the early phases of the infection (1). Other experiments have shown that topical application of phosphonoacetic acid (PAA), acyclovir, or phosphonoformic acid shortly after virus inoculation can prevent in most cases the colonization of ganglia with HSV (4, 6, 7, 13,15,17). Compounds such as arabinosyl adenine or arabinosyl adenine monophosphate are ineffective on comparably early application (5).…”

mentioning

confidence: 99%

Effects of topical applications of phosphonoacetate on colonization of mouse trigeminal ganglia with herpes simplex virus type 1

Klein¹,

Friedman‐Kien²,

Kaley³

et al. 1984

Antimicrob Agents Chemother

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The effects of topical application of phosphonoacetic acid on the colonization of mouse trigeminal ganglia by herpes simplex virus type 1 were examined. The results showed that the extent of colonization of ganglia by virus is related to the time elapsed between virus inoculation and application of this agent. In most cases, treatment started up to 12 h after inoculation prevented invasion of ganglia by virus HSV (4, 6, 7,13,15,17). Compounds such as arabinosyl adenine or arabinosyl adenine monophosphate are ineffective on comparably early application (5).There is no information, however, on the extent to which antiviral compounds can limit the amount of virus which invades the ganglia during the acute phase of infection. This information is important, since the amount of virus invading ganglia during the early phase of infection may determine the severity of the primary episode and the number of latently infected neurons and could also influence the frequency of subsequent recurrent episodes and the duration of HSV latency.In the present study, we determined the titer of infectious virus detectable in trigeminal ganglia of mice after a series of topical applications of PAA initiated at various intervals after virus inoculation. Furthermore, we monitored on a daily basis, during and after the end of the antiviral treatment, the evolution of virus titers in trigeminal ganglia and the inoculated skin area of HSV-infected mice. The results indicate that the interval between virus inoculation and initiation of antiviral treatments has an important influence on the amount of virus which accumulates in ganglia and determines, to a large extent, the outcome of the experimental HSV infection.MATERIALS AND METHODS Virus. HSV type 1 (HSV-1) strain S was used in all experiments. The maintenance of this strain, the preparation * Corresponding author. of stock virus, and the quantification of inocula have been described previously (3-7). This strain has the ability to invade the nervous system and to establish acute and latent infections in sensory ganglia.Inoculation of mice. Female hairless mice, strain HRS/J, obtained from Jackson Laboratories, Bar Harbor, Maine, were used in the experiments at the age of 6 to 8 weeks. They were inoculated percutaneously on a triangular area of the snout by rubbing a virus suspension containing 106 PFU/ml into the scarified skin. With this procedure, ca. 104 PFU were applied on the scarified skin of each mouse. Monitoring of infectious virus in sensory ganglia and skin specimens. At various intervals after inoculation, groups of mice were exsanguinated by heart puncture under pentobarbital sodium anesthesia. The day on which each group of mice was to be sacrificed had been randomly assigned after virus inoculation. Sensory ganglia were removed and homogenized immediately by sonication (Branson Sonifier Cell Disruptor 200). Skin specimens were removed from the inoculation area (ca. 0.25 cm2) and homogenized by sonication. The tissue suspension was clarified by centrifugation, and its viru...

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Herpes Simplex Acyclovir-Resistant Mutant in Experimental Keratouveitis

Boisjoly

Park²,

Pavan-Langston³

et al. 1983

Archives of Ophthalmology

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Ganglionic Herpes Simplex and Systemic Acyclovir

Cited by 21 publications

References 9 publications

Effects of 2,2'-O-cyclocytidine and acyclovir on latent herpes simplex virus in trigeminal ganglia of mice

Effects of 2,2'-O-cyclocytidine and acyclovir on latent herpes simplex virus in trigeminal ganglia of mice

Effects of topical applications of phosphonoacetate on colonization of mouse trigeminal ganglia with herpes simplex virus type 1

Herpes Simplex Acyclovir-Resistant Mutant in Experimental Keratouveitis

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