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Latency and reactivation of varicella zoster virus infections.

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Department of Neurology, Ulleval Hospital, Oslo, Norway.


Varicella zoster virus (VZV) is the causative agent of chickenpox (varicella) and shingles (zoster). The study of latency and reactivation has been hampered by the fact that the virus is strictly human and grows to low titres in tissue culture. Molecular biology techniques have opened a new era of VZV research. The site of VZV latency was determined to be sensory ganglia by Southern blotting and later by PCR technology. It was also demonstrated that the entire virus genome is present in the latently infected ganglia and that VZV is latent in multiple ganglia along the entire human neuraxis. Since the amount of latent VZV per cell is very low, the question of which cell type is involved in VZV latency could not be conclusively settled by the use of traditional in situ hybridization studies. However, we have now demonstrated the presence of latent VZV DNA in neurons only, by using a more sensitive method which employs a combination of in situ PCR and in situ hybridization. The transcriptional activity of VZV during latency is still not completely clear. Ganglia are small and the total amount of latent VZV is low, therefore conventional methods to detect latent VZV have proved limited. Nevertheless, the detection of a latent transcript from the SalI C region of the virus was demonstrated by Southern hybridization of cDNA synthesized from RNA isolated from latently-infected ganglia. Further studies have localized this transcript to the open reading frame of VZV gene 21. The study of VZV latency and reactivation has, until now, been dependent on the investigation of post mortem human tissue. However, simian varicella virus seems to be the simian counterpart to human VZV. The 2 viruses exhibit DNA homology as well as similarities in clinical, virological, and immunological features. Further studies of VZV infections may open new and possibly unpredictable opportunities in varicella virus research.

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