Reactivated and Latent Varicella-Zoster Virus in Human Dorsal Root Ganglia

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 24; pp. 10980 - 10984
• Main Authors: Lungu, Octavian, Annunziato, Paula W., Gershon, Anne, Staugaitis, Susan M., Josefson, Deborah, LaRussa, Philip, Silverstein, Saul J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 21.11.1995; National Acad Sciences; National Academy of Sciences
• Subjects: Antigens, Viral - metabolism; Artificial satellites; Base Sequence; Cytoplasm; DNA Primers - chemistry; DNA, Viral - analysis; Ganglia; Ganglia, Spinal - microbiology; Herpes zoster; Herpes Zoster - microbiology; Herpesvirus 3, Human - growth & development; Humans; In Situ Hybridization; Infections; Molecular Sequence Data; Neurons; Polymerase chain reaction; Varicella zoster encephalitis; varicella-zoster virus; Viral Envelope Proteins - metabolism; Virus Latency; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.24.10980

Ganglia obtained at autopsy were examined by in situ hybridization from one patient with zoster (also called herpes zoster or shingles), two varicella-zoster virus (VZV)-seropositive patients without clinical evidence of zoster, one VZV-seronegative child, and one fetus. Ganglia positive for VZV had a hybridization signal in both neuronal and nonneuronal satellite cells. Ganglia obtained from the fetus and from the seronegative infant were consistently negative for VZV. Two striking observations were evident regarding the presence of VZV DNA in ganglia obtained from the individual with zoster at the time of death. First, ganglia innervating the sites of reactivation and ganglia innervating adjacent sites yielded strongly positive signals in neurons and satellite cells, whereas ganglia from distant sites were rarely positive. Second, VZV DNA was found in both the nuclei and the cytoplasm of neurons innervating areas of zoster. However, in neurons innervating zoster-free areas, VZV DNA was found only in the nucleus of neurons and their supporting satellite cells. Immunohistochemistry with a fluorescent monoclonal antibody to the VZV glycoprotein gpI, a late virus protein, revealed a positive signal in the cytoplasm of ganglia with clinical evidence of reactivation. These results illustrate that both neuronal and satellite cells become latently infected following primary VZV infection. The presence of VZV DNA and gpI in the cytoplasm of neurons demonstrates productive infection following reactivation at the site of latency.