Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue

Liedtke, Wolfgang; Opalka, Bertram; Zimmermann, C.; Lignitz, Eberhard

doi:10.1016/0022-510x(93)90082-a

Cited by 119 publications

(67 citation statements)

References 26 publications

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“…With the recent findings of HSV DNA in the CNS of patients dying without encephalitis (2,43,68), it became important to determine whether i.c. injection of G207 might lead to reactivation of or recombination with latent virus, leading to a neurovirulent phenotype.…”

Section: Discussionmentioning

confidence: 99%

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Attenuated, Replication-Competent Herpes Simplex Virus Type 1 Mutant G207: Safety Evaluation in Mice

Sundaresan

Hunter

Martuza

et al. 2000

J Virol

137

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Herpes simplex virus type 1 (HSV-1) mutants that are attenuated for neurovirulence are being used for the treatment of cancer. We have examined the safety of G207, a multimutated replication-competent HSV-1 vector, in mice. BALB/c mice inoculated intracerebrally or intracerebroventricularly with 10 7 PFU of G207 survived for over 20 weeks with no apparent symptoms of disease. In contrast, over 80% of animals inoculated intracerebrally with 1.5 ؋ 10 3 PFU of HSV-1 wild-type strain KOS and 50% of animals inoculated intracerebroventricularly with 10 4 PFU of wild-type strain F died within 10 days. Similarly, after intrahepatic inoculation of G207 (3 ؋ 10 7 PFU) all animals survived for over 10 weeks, whereas no animals survived for even 1 week after inoculation with 10 6 PFU of KOS. After intracerebroventricular inoculation, LacZ expression was initially observed in the cells lining the ventricles and subarachnoid space; expression decreased until almost absent within 5 days postinfection, with no apparent loss of ependymal cells. G207 DNA could be detected by PCR in the brains of mice 8 weeks after intracerebral inoculation; however, no infectious virus could be detected after 2 days. As a model for latent HSV in the brain, we used survivors of an intracerebral inoculation of HSV-1 KOS at the 50% lethal dose. Inoculation of a high dose of G207 at the same stereotactic coordinates did not result in reactivation of detectable infectious virus or symptoms of disease. We conclude that G207 is safe at or above doses that were efficacious in mouse tumor studies.Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus which infects a wide range of cell types in different animals. Natural infections either follow a lytic, replicative cycle or establish latency. Latency is characterized by the long-term persistence of viral DNA in latently infected neurons, the lack of infectious or replicating virus, the lack of viral gene expression except for the latency-associated transcripts (LATs), and in some situations episodic reactivation of infectious virus (74). In humans, the natural host, HSV-1 causes a number of diseases, including gingivostomatitis and pharyngitis after primary oral-facial infection, recurrent herpes labialis, genital herpes, keratitis after eye infection, disseminated visceral infections in immunocompromised patients, hepatitis, and encephalitis after spread to the central nervous system (CNS) (13).HSV encephalitis is the most common CNS viral infection, occurring in two to three persons per million (13). Brain pathology is usually localized to the temporal lobe and limbic system, with asymmetric necrotizing encephalitis, inflammation, and hemorrhage (19, 33). The majority of cases of encephalitis occur in patients with recurrent HSV who are seropositive at onset of disease. Even with acyclovir therapy, mortality is about 20%, and about 20% of survivors have longterm morbidity, including cognitive abnormalities (23, 51).A number of animal models of HSV encephalitis involving spread from peripheral in...

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Section: Discussionmentioning

confidence: 99%

“…PCR primers in these studies could not differentiate HSV-1 from HSV-2. In a study of 109 human corpses at forensic postmortem, 16% were positive for HSV-1 DNA in the olfactory bulbs, whereas 72% of the trigeminal ganglia were positive (43). In animal models, HSV DNA can often be detected in the CNS of animals surviving HSV-induced encephalitis (17,67).…”

mentioning

confidence: 99%

Attenuated, Replication-Competent Herpes Simplex Virus Type 1 Mutant G207: Safety Evaluation in Mice

Sundaresan

Hunter

Martuza

et al. 2000

J Virol

137

View full text Add to dashboard Cite

show abstract

“…For instance, skin infection of herpes zoster is more frequent in aged population (Schmader & Dworkin, 2008) and with situations which impair cellular immunity (Schmader, 1999). Latent Herpes simplex virus existance in trigeminal ganglion is significantly more frequent in elderly individuals as compared to younger adults, which is concordant with the fact that herpes simplex encephalitis frequency is higher in aged population (Liedtke et al, 1993). This data is reflecting the poor immunological response to herpes simplex virus with increased age.…”

Section: Immune Alterationsmentioning

confidence: 73%

Encephalitis in Elderly Population

Öztürk¹,

Ege²

2011

Pathogenesis of Encephalitis

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“…HSV1 распространяется от слизистой оболочки носа в ЦНС по обонятельным нервам [1], достигает обонятельной луковицы и затем движется по ветвям тройничного нерва [2]. Вновь продуцированные вирионы HSV1 мигрируют в струк-туры лимбической системы -гипоталамус, гиппокамп и миндалину [1,3], поэтому при HSV энцефалите наибольшие повреждения выявляют в лимбической системе [4]. Обонятельный тракт также являет путем проникновения в ЦНС герпеса 6 типа (HHV6) [5,6].…”

Section: Ukrainianunclassified

Viruses in human central nervous system — invasion, transmission, and latency: a literature review

Tsymbalyuk¹,

Vasileva²

2017

Ukr Neurosurg J

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Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue

Cited by 119 publications

References 26 publications

Attenuated, Replication-Competent Herpes Simplex Virus Type 1 Mutant G207: Safety Evaluation in Mice

Attenuated, Replication-Competent Herpes Simplex Virus Type 1 Mutant G207: Safety Evaluation in Mice

Encephalitis in Elderly Population

Viruses in human central nervous system — invasion, transmission, and latency: a literature review

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