Herpesvirus Infections of the Human Central Nervous System

Olson, Lloyd C.; Buescher, Edward L.; Artenstein, Malcolm S.; Parkman, Paul D.

doi:10.1056/nejm196712142772401

Cited by 210 publications

(50 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Herpes encephalitis has been observed in patients with a previous history of cold sores and in patients proven to be seropositive before onset of encephalitis (Nahmias et al, 1982;Olson et al, 1967). Recurrent herpes labialis and recurrent herpes genitalis by definition occur in seropositive individuals.…”

Section: Introductionmentioning

confidence: 99%

Delayed IgG-mediated Clearance of Herpes Simplex Virus Type 1 from the CNS but Not Footpad during the Early Stages of Infection: Possible Result of Relative Integrity of the Blood-Brain Barrier

McKendall

1983

Journal of General Virology

View full text Add to dashboard Cite

SUMMARYFollowing footpad inoculation in mice, herpes simplex virus type 1 spreads along nerves to the spinal cord where a myelitis causes hind limb paralysis beginning on day 6. Neutralizing antibody effectively prevents this illness only if given within 72 h. We therefore studied the timing of blood-brain barrier (BBB) disruption relative to the appearance of virus and inflammatory cell infiltrates in the spinal cord, Virus was detectable in dorsal root ganglion and spinal cord explants by 48 h. By 72 h, mononuclear cell infiltrates were evident in the spinal cord. By day 4, high titres of virus were demonstrable in the spinal cord. On day 6 t2sI-labelled IgG tracers penetrated the spinal cord BBB. In addition, using a passive transfer model, mice given neutralizing IgG completely cleared footpad virus within 72 h while brain virus titres were unaffected by IgG treatment up to day 7. These observations indicate that the BBB may prevent IgG-mediated virus clearance during the early stages of infection. INTRODUCTIONHerpes encephalitis has been observed in patients with a previous history of cold sores and in patients proven to be seropositive before onset of encephalitis (Nahmias et al., 1982;Olson et al., 1967). Recurrent herpes labialis and recurrent herpes genitalis by definition occur in seropositive individuals. These facts suggest that antibody is ineffective in control of herpetic infections. However, animal models continue to document an important role for antibody in experimental herpes simplex virus (HSV) infections (McKendall et al., 1979;Oakes & Rosemond-Hornbeak, 1978;Davis et al., 1979;Worthington et al., 1980). Most studies, including ours, have shown that antibody must be given within 48 to 72 h after peripheral inoculation of virus in order to be effective. This requirement was surprising since the clinical disease we observe in our studies does not appear until 6 days after footpad inoculation at which time a myelitis is responsible for the posterior limb paralysis which develops. Therefore, we postulated that the blood-brain barrier (BBB) may prevent IgG access to the spinal cord.To test this postulate we performed a series of studies using both the footpad model of HSV type 1 (HSV-I) myelitis and an experimental model of HSV-1 encephalitis caused by direct intracerebral (i.c.) inoculation of virus. In the footpad model we studied the kinetics of virus spread to the spinal cord, the appearance of myelitis detected by histopathology and the integrity of the BBB detected by leakage of 1,,5 I-labelled IgG into the spinal cord. Correlation of these findings indicated that leakage across the BBB did not occur until several days after virus and histopathological lesions were detectable in the spinal cord. Furthermore, systemic treatment with neutralizing IgG was effective in clearing virus from footpad inoculation sites but ineffective in clearing i.c. inoculated virus from brain tissue. These observations indicate that virus replication proceeds without restriction by antiviral IgG during the early ...

show abstract

Section: Introductionmentioning

confidence: 99%

Delayed IgG-mediated Clearance of Herpes Simplex Virus Type 1 from the CNS but Not Footpad during the Early Stages of Infection: Possible Result of Relative Integrity of the Blood-Brain Barrier

McKendall

1983

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…Herpesvirus hominis (HVH) is the causative agent of several life-threatening diseases in humans including encephalitis in adults (22), and a generalized infection of neonates with or without central nervous system involvement (20,23). Although infection of human newborn infants with HVH type 2 occurs relatively infrequently, it is associated with a 70% mortality rate and neurological sequelae in 50% of the survivors (20).…”

mentioning

confidence: 99%

Herpesvirus hominis Infection in Newborn Mice: Comparison of the Therapeutic Efficacy of 1-β- d -Arabinofuranosylcytosine and 9-β- d -Arabinofuranosyladenine

Kern

Overall²,

Glasgow³

1975

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Intranasal inoculation of newborn mice with Herpesvirus hominis type 2 provides an experimental infection that closely resembles disseminated herpesvirus infection of human newborn infants. After inoculation of mice, the virus multiplies in the respiratory tract and is disseminated through the blood to the liver and spleen and to the brain by both a viremia and nerve route transmission. Although therapy with 1-β- d -arabinofuranosylcytosine (ara-C) did not reduce final mortality, it did increase the mean survival time by 1 day. This effect on the mean survival time was associated with a 1-day delay in the appearance of herpesvirus in the blood, liver, and spleen and a reduction of virus replication in lung and brain for 1 day as compared with untreated control animals. Treatment with 9-β- d -arabinofuranosyladenine (ara-A) likewise had no effect on final mortality, but increased the mean survival time by 2 days. Therapy with ara-A delayed or suppressed virus replication in blood, lung, liver, spleen, and brain for 2 days. Although treatment with either ara-C or ara-A in this experimental H. hominis type 2 infection resulted in a temporary delay and/or suppression of viral replication in several target organs, neither compound was completely effective in inhibiting viral replication or in protecting animals from eventual death due to the infection.

show abstract

“…Although it is sometimes insisted that an inflammatory response in the cerebrospinal fluid tends to be more prominent in herpesvirus infection than in enterovirus infection, to differentiate them by the cerebrospinal fluid findings is impossible. Our case series showed that the cells in the cerebrospinal fluid ranged from 0 to 370/µl, and a study of herpesvirus infection showed 4 to 755/µl (Olson et al, 1967). The results are therefore highly variable among cases, and are not sufficiently informative to speculate on the causative agent.…”

Section: Laboratory Datamentioning

confidence: 68%