Effects of Idoxuridine on Herpesvirus hominis Encephalitis and Disseminated Infections in Marmosets

Cho, C. T.; Liu, C.; Voth, Douglas W.; Feng, Kai

doi:10.1093/infdis/128.6.718

Cited by 21 publications

(8 citation statements)

References 13 publications

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“…12,13 The common marmosets succumbed much sooner than the owl monkey, showing severe symptoms usually around 6 days post-injection, and their brains also displayed marked infection with HSV, with far more extensive HSV immunopositivity than seen in the owl monkeys. This survival time corresponds with the findings of Cho et al, 4 who reported an average survival time of 8 days after injecting 10 5 PFU HSV-1 intracerebrally into two marmosets. In our study, the marmoset brains showed substantially less inflammation in the cerebral hemispheres, but had classical histological findings of encephalitis in the brain stem, including acute and chronic inflammation, microglia, and Cowdry type A inclusions.…”

Section: Discussionsupporting

confidence: 90%

“…This finding is in accordance with reports from Cho et al, who were unable to isolate the virus in liver tissue of either one of two of their marmosets, which succumbed to the intracerebral infection with 10 5 PFU HSV-1 on day 6 and 10, respectively. 4 A striking finding is that the PCR of the brain tissue in the common marmoset was predominantly positive whereas only one out of five owl monkeys showed a positive brain tissue PCR, corresponding to the impressive histopathological findings in these animals. Another intriguing finding in the owl monkey group was the loss of the viral DNA in the serum in two out of five animals (40%) receiving distinctively different HSV-1 F-strain titers (5 Â 10 3 and 10 6 PFU/ml, respectively).…”

Section: Discussionmentioning

confidence: 92%

“…The common marmoset (Callithrix jacchus), another yet smaller New World primate, has been shown to be susceptible to HSV infection [2][3][4][5] and more recently, the marmoset has been proposed as experimental model for allergic encephalomyelitis, 6 for cytokine and gene therapy studies. [7][8][9] Common marmosets are bred in designated Primate Research Facilities within the United States and as such these animals are readily available at most biomedical research centers, thus facilitating experimental planning and potentially accelerating transitions into important clinical trials.…”

Section: Introductionmentioning

confidence: 99%

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Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study

et al. 2003

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The owl monkey (Aotus trivirgatus) has served as the standard non-human primate model of herpes simplex virus-1 (HSV-1) infection because it is highly susceptible to HSV-1 encephalitis. Owl monkeys, however, are expensive, difficult to obtain, and difficult to maintain in captivity, thus greatly hampering the efficiency of preclinical gene therapy trials for brain tumors using HSV-1-based vectors. We have therefore compared the susceptibility of the common marmoset (Callithrix jacchus) with the owl monkey in a model of intracerebral inoculation of wildtype HSV-1 F-strain at increasing titers. The common marmosets consistently succumbed earlier to viral encephalitis than the owl monkeys.The histological evaluation of the common marmoset revealed extensive HSV-1 infection with a concomitant yet less marked inflammatory response compared to the owl monkeys. PCR for HSV-1 demonstrated a similar extra-CNS shedding route in both experimental models. Our findings show that the common marmoset is at least as susceptible to intracerebral HSV-infection as the owl monkey and that it can therefore serve as a valid and reliable experimental model for the important preclinical safety tests of HSV-based therapeutic viral vector constructs in the brain.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study

et al. 2003

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“…In addition, the efficacies of various ntly, considerable effort has been dedi-nontoxic doses of ACV were compared with the ;o treating HSV encephalitis. Systemic effectiveness of the maximum tolerated dose of with iododeoxyuridine for the treatment ara-A, a compound recently approved by the encephalitis was initially met with some Food and Drug Administration for use in herasm (3,11). Two placebo-controlled, dou-petic infections, including human herpetic end studies designed to evaluate the cephalitis.…”

Section: Tionmentioning

confidence: 99%

Therapy of Experimental Herpes Simplex Encephalitis with Aciclovir in Mice

Park

Pavan-Langston

McLean

et al. 1979

Antimicrob Agents Chemother

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This report is concerned with the capacities of aciclovir to protect mice challenged intracerebrally with multiple lethal doses of type 1 herpes simplex virus and to control multiplication of this virus in the brain. With treatment initiated 12 h after inoculation and continued for 4 consecutive days, aciclovir administered subcutaneously in daily doses ranging from 40 to 100 mg/kg led to 21-day survival rates of from 33 to 73% and reduced virus titers by 1 to 1,h x 4 logs on postchallenge day 8. The therapeutic accomplishments of the 100-mg/kg doses of aciclovir were comparable to those of 1,000-mg/kg doses of vidarabine (9-,B-Darabinofuranosyladenine); however, as measured by impact on body weight, aciclovir was better tolerated than vidarabine at these similarly effective doses.Aciclovir [ACV; 9-(2-hydroxyethoxymethyl)-guanine, or acycloguanosine] has been introduced recently as a potent and selective antiviral agent against herpes simplex virus type 1 (HSV-1) and 7,9,13,16). In vitro this compound also inhibits the multiplication ofvaricella zoster virus, cytomegalovirus, and B virus but has no effect on vaccinia virus, adenovirus type 5, and a range of ribonucleic acid viruses (16). ACV penetrates infected cells to a greater degree than uninfected cells (6). Once introduced into cells, it is converted to a monophosphate form by an HSV-specific thymidine kinase and eventually to a triphosphate form. ACV triphosphate then acts by inhibition of viral DNA polymerase. An additional selective advantage is that ACV triphosphate has a 30-foldgreater affinity for viral deoxyribonucleic acid polymerase than for cellular deoxyribonucleic acid polymerase in vitro (6,7). In the present study we evaluated the therapeutic efficacy of ACV for the herpes encephalitis by observing the capacities of ACV to protect mice inoculated intracerebrally with HSV-1 and to control the multiplication of this virus in the brain. More Forty-five mice inoculated with saline were divided into three equal subgroups which were treated as follows: (i) phosphate-buffered saline, 0.2 ml/day; (ii) ACV, 100 mg/kg per day; or (iii) ara-A, 1,000 mg/kg per day. Treatments were initiated 12 h after the inoculation of HSV-1 or saline and consisted of subcutaneous injections of two divided doses per day for 4 days. The mice were weighed on days 0, 2, 4, 8, 10, 14, and 16 after the inoculation to monitor weight change. The

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“…In the natural host ( Homo sapiens ), infection with HSV‐1 is usually inapparent or causes mild, recurrent orofacial lesions [2, 16, 35]. In non‐human primates, fatalities were reported in the 1960 and 1970s following natural infection with a strain of HSV that was probably HSV‐1 in splenectomized white‐handed gibbons ( Hylobates lar ), owl monkeys ( Aotus trivirgatus ), tree shrews ( Tupaia glis ), and lemurs ( Lemur catta ) and experimentally in tamarins ( Saguinus oedipus ) [6, 17, 20, 24, 31]. More recently, HSV‐1 was shown to cause mild or asymptomatic infections in gorillas ( Gorilla gorilla ), orangutans ( Pongo pygmaeus ), chimpanzees ( Pan troglodytes ), and gibbon apes ( Hylobates spp.…”

Section: Introductionmentioning

confidence: 99%

Naturally occurring fatal herpes simplex virus 1 infection in a family of white‐faced saki monkeys (Pithecia pithecia pithecia)

Schrenzel

Osborn

Shima

et al. 2003

J of Medical Primatology

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A family of three white-faced saki monkeys (Pithecia pithecia pithecia) died 48-96 hours after the onset of anorexia, nasal discharge, pyrexia and oral ulceration. One animal also had clonic seizures. Lesions found post-mortem consisted of oral and esophageal ulcers, hepatic and intestinal necrosis, meningoencephalitis and sporadic neuronal necrosis. Intranuclear inclusion bodies and syncytial cells were present in oral lesions and affected areas of liver. Herpes simplex virus 1 (HSV-1) was identified as the etiology of disease by virus isolation, polymerase chain reaction, or in situ hybridization in all three animals. Immunohistochemistry for detection of apoptotic DNA and activated caspase-3 showed significant levels of apoptosis in oral and liver lesions and occasional apoptotic neurons in the brain. These findings demonstrate the vulnerability of white-faced saki monkeys to HSV-1 and provide initial insight into the pathogenesis of fatal HSV-1-induced disease, indicating that apoptosis plays a significant role in cell death.

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Effects of Idoxuridine on Herpesvirus hominis Encephalitis and Disseminated Infections in Marmosets

Cited by 21 publications

References 13 publications

Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study

Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study

Therapy of Experimental Herpes Simplex Encephalitis with Aciclovir in Mice

Naturally occurring fatal herpes simplex virus 1 infection in a family of white‐faced saki monkeys (Pithecia pithecia pithecia)

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