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Biomedical subjects

D H Gilden

Publications and source records attributed to D H Gilden.

At least 19 recordsLinked to original sources
PubMed1992

Localization of herpes simplex virus and varicella zoster virus DNA in human ganglia.

Human dorsal root ganglia from 14 randomly autopsied adults and 1 infant (all seropositive for both herpes simplex virus [HSV] and varicella zoster virus [VZV]) were examined for latent HSV-1 and VZV DNA by polymerase chain reaction. Thoracic ganglionic DNA from all subjects and trigeminal ganglionic DNA from 11 adults were analyzed. HSV-1 DNA was detected in trigeminal ganglia from 8 of 11 (73%) adults and in thoracic ganglia from 2 of 14 (14%) adults. VZV DNA was detected in trigeminal ganglia from 10 of 11 (91%) adults and in thoracic ganglia from 12 of 14 (86%) adults. None of the DNA samples were positive with primers specific for HSV-2. These findings indicate the presence of latent HSV-1 and VZV DNA in trigeminal ganglia and latent VZV DNA in thoracic ganglia of most seropositive adults. Furthermore, although HSV-1 latency most commonly develops in trigeminal ganglia, we also show for the first time the presence of HSV-1 latency in thoracic ganglia. Finally, both viruses can become latent in the same trigeminal ganglion.

Base Sequence↗
PubMed1992

Prevalence and distribution of latent simian varicella virus DNA in monkey ganglia.

We used polymerase chain reaction to analyze the prevalence and distribution of latent simian varicella virus (SVV) in ganglionic and nonganglionic tissues from nine African green monkeys experimentally infected with SVV. Primers specific for three different regions of the SVV genome were used for amplification. SVV DNA sequences were detected in trigeminal ganglia from seven of nine monkeys and in thoracic ganglia from seven of nine monkeys. Analysis of DNA from nonneuronal tissues of three monkeys and from adrenal glands of nine monkeys revealed the presence of SVV-specific sequences in the adrenal gland of one monkey. The results indicate that, like human varicella, SVV becomes latent primarily in ganglia at multiple levels of the neuraxis, and more than one region of the SVV genome is present in latently infected ganglia. SVV latency in primates may be a useful model for varicella latency in humans.

Animals↗
PubMed1992

Molecular analysis of simian varicella virus DNA.

Clinical and pathological studies indicate that simian varicella virus (SVV) infection in primates is the counterpart of human varicella zoster virus (VZV) infection. The SVV and VZV genomes are also similar in size and structure. To extend studies of SVV DNA, we analyzed virus DNA from African green monkey kidney cells infected with the Delta-herpes-virus strain of SVV. The infectivity of SVV DNA was 88 PFU/micrograms. The buoyant density of SVV DNA, determined by isopycnic banding in CsCl gradients, was 1.700 +/- 0.002 g/ml, corresponding to a G + C molar ratio of 40.8%. The size of SVV DNA, estimated by analysis of restriction endonuclease digestion products and pulsed-field gel electrophoresis was 125.1 and 124.9 kbp, respectively. Electron microscopy of SVV DNA revealed a long region of 110.0 kbp, a unique short (Us) region of 5.1 kbp, and inverted repeat regions of 7.5 kbp flanking the Us. An EcoRI map of SVV DNA revealed two fragments not previously reported; our complete Pstl map also shows some differences. Mapping of SVV DNA with an additional restriction enzyme, measurement of full-length SVV DNA molecules, and the first use of pulsed-field electrophoresis to size SVV DNA, confirm and extend Gray's recent finding that SVV DNA has the same size and molecular configuration as VZV. We also show for the first time that the density of SVV DNA is similar to that of VZV DNA and that SVV DNA is infectious.

Animals↗
PubMed1992

Peripheral blood mononuclear cells of the elderly contain varicella-zoster virus DNA.

Peripheral blood mononuclear cells (PBMC) from humans of different ages were analyzed for DNA sequences specific for varicella-zoster virus (VZV) genes 29 and 62 by polymerase chain reaction (PCR). Neither VZV gene was detected in DNA from umbilical cord blood PBMC of 10 infants or from blood PBMC of two 3-year-old children. In 22 humans less than 60 years old, gene 29 was not detected, and gene 62 was detected in only one subject. In 33 humans greater than 60 years old, including patients with postherpetic neuralgia, PBMC from 4 subjects contained gene 29, 4 contained gene 62, and 1 contained both genes. The presence of VZV DNA correlated significantly with age (P less than .05, chi 2 and logistic regression analysis), but not with gender or postherpetic neuralgia.

Adult↗
PubMed1992

Restricted transcription of varicella-zoster virus in latently infected human trigeminal and thoracic ganglia.

Normal human trigeminal and thoracic ganglia latently infected with varicella-zoster virus (VZV) were identified by polymerase chain reaction (PCR). Total RNA was extracted from these ganglia and treated with DNase until ganglionic RNA was free of VZV DNA as determined by PCR. Radiolabeled cDNA synthesized by priming with random oligonucleotides was hybridized to Southern blots containing recombinant clones that spanned greater than 95% of the VZV genome. The single region of the VZV genome detected was the 12.5-kb SalI C fragment located in the unique long segment of the viral genome. Two additional regions of the VZV genome, EcoRI G and SalI B, were detected in RNA from adult dorsal root ganglia and infant nervous system tissue.

Adult↗
PubMed1992

Varicella-zoster virus reactivation without rash.

Reactivation of varicella-zoster virus (VZV) leads to localized zoster (shingles), a syndrome characterized by pain and a vesicular rash. Rarely, patients experience radicular pain without zosteriform rash, cases that have been regarded as zoster sine herpete (zoster without rash). Virologic evidence for zoster sine herpete is sparse. However, VZV can produce other neurologic and visceral diseases in the absence of rash or radicular pain. The clinical and virologic features of zoster sine herpete and other disorders produced by VZV without rash are reviewed. Evidence is also presented for the detection of VZV DNA in human blood mononuclear cells of elderly individuals in the absence of skin lesions or other VZV-associated neurologic or systemic disease.

Aged↗
PubMed1992

Acute simian varicella infection. Clinical, laboratory, pathologic, and virologic features.

Five African green monkeys inoculated intratracheally with 7.5 x 10(3) to 1.4 x 10(5) plaque-forming units of simian varicella virus (SVV) were subjected to clinical, laboratory, pathologic, and virologic analyses to study the pathogenesis of acute varicella. All animals developed viremia and rash and were sacrificed 8 to 11 days post-infection. No serum was available for postmortem serologic studies. Examination of multiple organs for pathologic changes and for SVV-specific antigen and nucleic acid revealed inflammation, hemorrhagic necrosis, and intranuclear Cowdry A inclusions in liver, lung, lymph node, and spleen; mild inflammation without necrosis in adrenal gland, kidney, and bone marrow, and SVV-specific antigen and nucleic acids in all viscera examined. No pathologic changes, SVV antigen or nucleic acids were detected in the spinal cord or in the brain from any of the monkeys. Ganglia revealed mild inflammation but no necrosis, and intranuclear inclusion bodies in non-neuronal cells of one trigeminal ganglion; SVV antigen and nucleic acids were detected in both non-neuronal and neuronal cells in ganglia. The pathologic and virologic findings in viscera are consistent with those described in viscera of humans with disseminated zoster, but the mild inflammatory changes in ganglia during acute simian varicella infection contrast with the extensive hemorrhagic necrosis and intranuclear inclusion bodies seen in human ganglia after disseminated varicella or zoster. Nevertheless, these studies show that ganglia become infected with varicella virus during primary infection, although the route of primary ganglionic infection remains to be determined, and indicate the possible usefulness of the SVV model to study varicella pathogenesis in humans.

Acute Disease↗
PubMed1991

Type-specific identification of herpes simplex and varicella-zoster virus antigen in autopsy tissues.

To identify antigens of herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV) in human tissue, polyclonal antisera and an immunoperoxidase method were used to examine formalin-fixed, paraffin-embedded tissues from autopsy cases and experimentally infected animals. These antisera readily distinguished between HSV and VZV antigen, with no evident cross-reactivity. Antiser ato HSV-1 and HSV-2 were more strongly reactive with antigen of the homologous virus than with that of heterologous virus. This difference in immunoreactivity was used to discriminate between HSV-1 and HSV-2 antigens in experimentally infected animal tissues containing HSV antigens of known type and, by extrapolation, to distinguish between these antigens in human autopsy tissues. Thus, with appropriate antisera and tissue controls, HSV-1, HSV-2, and VZV can be identified in paraffin sections.

Adult↗
PubMed1991

Preherpetic neuralgia.

We have encountered six zoster patients whose pain preceded rash by 7 to more than 100 days. Pain was severe, burning, and radicular, and located both in dermatomes different from, as well as in, the area of eventual rash. Two patients ultimately developed disseminated zoster with neurologic complications, one of zoster paresis, and the other, a fatal zoster encephalitis; both had been taking long-term, low-dose steroids. A third case of preherpetic neuralgia developed in a patient with prior metastatic carcinoma, and another case in a patient with an earlier episode of brachial neuritis. The final two cases of preherpetic neuralgia developed in individuals with no underlying disease. An extended period of pain before the onset of zoster rash has gone largely unrecognized.

Antigens, Viral↗
PubMed1990

Trans-activation of viral tk promoters by proteins encoded by varicella zoster virus open reading frames 61 and 62.

Plasmids containing the varicella zoster virus (VZV) open reading frames (ORFs) 61 and 62 were used in a transient co-transfection assay to test for trans-activation of the VZV and herpes simplex virus type 1 (HSV-1) thymidine kinase (tk) promoters. The trans-activating potential of the polypeptides encoded by these VZV ORFs, designated p51 and p140, was compared to that of their HSV-1 homologs ICP0 and ICP4, respectively. VZV p51 was functionally inactive in this system while p140 appeared to be a much stronger transcriptional activator than ICP4. Co-transfection of plasmids encoding VZV p140 and HSV-1 ICP0 resulted in a synergistic activation of the reporter gene as has been shown for the combination of ICP4 and ICP0.

Herpesvirus 3, Human↗
PubMed1989

Persistence of varicella-zoster virus DNA in blood mononuclear cells of patients with varicella or zoster.

Varicella-zoster virus (VZV) DNA was detectable by in-situ hybridization in blood mononuclear cells (MNCs) of patients with varicella or zoster for 2-56 days after the onset of a rash. VZV DNA was present in many MNCs from one acute varicella patient 2 days after the onset of the rash and was rarely found in MNCs during acute zoster, convalescent zoster, and convalescent varicella. The morphology of MNCs containing VZV was heterogenous, although most viral-DNA-containing MNCs were large monocytoid cells. Serial examination of blood MNCs from one adult with varicella revealed VZV DNA up until 8 weeks, but not 16 weeks, after the appearance of the rash; parallel studies in four zoster patients showed VZV DNA up until 3 weeks, but not later than 7 weeks after the appearance of the rash. These results indicate that MNCs become infected with VZV during the primary encounter with VZV (varicella) and during reactivation (zoster) and that infection continues for weeks after the onset of the skin rash. Furthermore, the detection of VZV DNA in blood MNCs of uncomplicated zoster patients coincides with the period during which these patients experience pain.

Adult↗
PubMed1988

Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia.

Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia.

Adult↗
PubMed1988

Expression of varicella-zoster virus in blood mononuclear cells of patients with postherpetic neuralgia.

Postherpetic neuralgia (PHN), the most frequent complication of varicella-zoster virus (VZV) reactivation, is characterized by pain that persists for greater than 1 mo and often for years after zoster rash. To examine whether PHN might be related to reactivation of VZV, blood mononuclear cells of patients with PHN were tested for the presence of VZV DNA and proteins. VZV DNA was detected in the mononuclear cells of one PHN patient. VZV-specific proteins were detected in mononuclear cells of two acute-varicella patients, one acute zoster patient, and six elderly patients with PHN, but these VZV-specific proteins were not detected in three elderly zoster patients without PHN. Furthermore, pulse-chase experiments revealed further processing or degradation of VZV-specific proteins in the mononuclear cells. These findings strongly suggest that persistence, reactivation, and expression of VZV may result in PHN.

Chickenpox↗
PubMed1988

Detection of antibodies to varicella-zoster virus proteins in sera from the elderly.

Sera from 40 elderly individuals ranging in age from 60 to 94 years were tested for the presence of antibodies to varicella-zoster virus (VZV)-specific proteins. Sodium dodecylsulfate polyacrylamide gel electrophoresis analysis of lysates of VZV-infected BSC-1 cells labeled with either [35S]methionine or [3H]mannose and immunoprecipitated with human sera revealed the variable presence of VZV-specific antibodies to four VZV glycoproteins (gpI, gpII, gpIII, and gpIV), and three nonglycosylated proteins (155, 140, 32 kilodaltons, kDa). The predominant antibody response in the sera from the elderly was to VZV gpII and the 155-kDa species. In addition, some sera from elderly individuals without an identifiable history of varicella or zoster contained antibodies to VZV proteins, suggesting a possible subclinical infection in these patients. Finally a history of zoster in the elderly was significantly correlated (p = 0.02) with the presence of antibody to gpIV.

Aged↗
PubMed1988

Chronic progressive varicella-zoster virus encephalitis in an AIDS patient.

A patient with AIDS developed chronic, progressive encephalitis. Pathologic changes indicated that the encephalitis was produced primarily by a human herpesvirus. Hybridization of radiolabeled RNA probes transcribed from cloned DNA fragments of varicella-zoster virus (VZV), herpes simplex virus, cytomegalovirus, and the human immunodeficiency virus to DNA extracted from the patient's brain identified VZV as the causative agent. The results suggest that VZV should be considered in the differential diagnosis of chronic encephalitis of unknown etiology, particularly in immunosuppressed patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Detection of varicella-zoster virus nucleic acid in neurons of normal human thoracic ganglia.

Tissue sections from four normal human thoracic ganglia were hybridized in situ with a varicella-zoster virus-RNA probe. Varicella-zoster virus was detected in two of four ganglia, localized exclusively in neurons. The detection of latent varicella-zoster virus genetic material in thoracic ganglia provides further evidence of varicella-zoster virus latency at multiple levels of the human neuraxis and supports the notion that the neuron is the primary site of herpesvirus latency.

DNA, Viral↗
PubMed1987

Varicella-zoster virus infection of human mononuclear cells.

Varicella-zoster virus (VZV) DNA was detected in mononuclear cells (MNC) of 7 humans with acute zoster 1-23 days after the onset of skin lesions. To further study the interaction of VZV with human MNC, cells obtained from seropositive normal donors were infected with VZV and analyzed for the presence of viral DNA and proteins. VZV-DNA was detected in T, B, and OKM 1 (monocyte-macrophage) positive cells, and virus-specific proteins were demonstrated by indirect immunofluorescence and immunoprecipitation. Hybridization studies revealed that VZV-DNA did not replicate in human MNC.

Adult↗