Abstract
Varicella-zoster virus (VZV) is a human herpesvirus that causes varicella (chicken pox) as a primary infection and, after a variable period of latency in trigeminal and dorsal root ganglia, reactivates to cause herpes zoster (shingles). Both of these conditions may be followed by a variety of neurological complications, especially in immunocompromised individuals such as those with human immunodeficiency virus (HIV) infection. There have been a number of conflicting reports regarding the cellular location of latent VZV within human ganglia. To address this controversy we examined fixed wax-embedded trigeminal ganglia from 30 individuals obtained at autopsy, including 11 with HIV infection, 2 neonates, and 17 immunocompetent individuals, for the presence of latent VZV. Polymerase chain reaction (PCR), in situ hybridization, and PCR in situ amplification techniques with oligonucleotide probes and primer sequences to VZV genes 18, 21, 29, and 63 were used. VZV DNA in ganglia was detected in 15 individuals by using PCR alone, and in 12 individuals (6 normal non-HIV and 6 positive HIV individuals, but not neonatal ganglia) by using PCR in situ amplification. When in situ hybridization alone was used, 5 HIV-positive individuals and only 1 non-HIV individual showed VZV nucleic acid signals in ganglia. In all of the VZV-positive ganglia examined, VZV nucleic acid was detected in neuronal nuclei. Only occasional nonneuronal cells contained VZV DNA. We conclude from these studies that the neuron is the predominant site of latent VZV in human trigeminal ganglia.
MeSH Terms
Acquired Immunodeficiency Syndrome/pathology,virology
Adult
Autopsy
Child
Child, Preschool
DNA Primers
Female
Herpesvirus 3, Human/genetics,isolation & purification,physiology
Humans
In Situ Hybridization
Infant
Infant, Newborn
Male
Middle Aged
Neurons/pathology,virology
Oligonucleotide Probes
Polymerase Chain Reaction/methods
Sudden Infant Death
Trigeminal Ganglion/pathology,virology
Virus Latency
Chemicals
DNA Primers
Oligonucleotide Probes
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kennedy P G
Glasgow University Department of Neurology, Institute of Neurological Sciences, Southern General Hospital National Health Service Trust, Glasgow G51 4TF, United Kingdom.P.G.Kennedy@clinmed.gla.ac.uk
Grinfeld E
Gow J W
References (13)
13 references, click to expand
-
Varicella-zoster virus transcription in human trigeminal ganglia.
Virology. 1993 Mar;193(1):193-200
PMID: 7679857
-
Molecular biology of herpes simplex virus type 1 latency in the nervous system.
Mol Neurobiol. 1993 Summer;7(2):137-59
PMID: 8396944
-
Varicella-zoster virus (VZV) transcription during latency in human ganglia: construction of a cDNA library from latently infected human trigeminal ganglia and detection of a VZV transcript.
J Virol. 1994 Dec;68(12):7900-8
PMID: 7966580
-
The vasculopathy of varicella-zoster virus encephalitis.
Ann Neurol. 1995 Jun;37(6):784-90
PMID: 7778852
-
Reactivated and latent varicella-zoster virus in human dorsal root ganglia.
Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10980-4
PMID: 7479921
-
Detection of latent varicella zoster virus DNA and human gene sequences in human trigeminal ganglia by in situ amplification combined with in situ hybridization.
Arch Virol. 1995;140(11):2055-66
PMID: 7503701
-
Comparative biology of latent varicella-zoster virus and herpes simplex virus infections.
J Infect Dis. 1992 Aug;166 Suppl 1:S13-23
PMID: 1320646
-
Expression of protein encoded by varicella-zoster virus open reading frame 63 in latently infected human ganglionic neurons.
Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2122-4
PMID: 8700895
-
Varicella-zoster virus RNA in human trigeminal ganglia.
Lancet. 1983 Oct 8;2(8354):814-6
PMID: 6137648
-
Detection of varicella-zoster virus nucleic acid in neurons of normal human thoracic ganglia.
Ann Neurol. 1987 Sep;22(3):377-80
PMID: 2823688
-
Patterns of gene expression and sites of latency in human nerve ganglia are different for varicella-zoster and herpes simplex viruses.
Proc Natl Acad Sci U S A. 1988 Dec;85(24):9773-7
PMID: 2849116
-
Varicella and herpes zoster: a perspective and overview.
J Infect Dis. 1992 Aug;166 Suppl 1:S1-6
PMID: 1320645
-
Varicella-zoster virus (VZV) transcription during latency in human ganglia: detection of transcripts mapping to genes 21, 29, 62, and 63 in a cDNA library enriched for VZV RNA.
J Virol. 1996 May;70(5):2789-96
PMID: 8627753