Varicella-zoster virus infection of human neural cells in vivo.
Varicella-zoster virus (VZV) establishes latency in sensory ganglia and causes herpes zoster upon reactivation. These investigations in a nonobese diabetic severe combined immunodeficient mouse-human neural cell model showed that VZV infected both neurons and glial cells and spread efficiently from cell to cell in vivo. Neural cell morphology and protein synthesis were preserved, in contrast to destruction of epithelial cells by VZV. Expression of VZV genes in neural cells was characterized by nuclear retention of the major viral transactivating protein and a block in synthesis of the predominant envelope glycoprotein. The attenuated VZV vaccine strain retained infectivity for neurons and glial cells in vivo. VZV gene expression in differentiated human neural cells in vivo differs from neural infection by herpes simplex virus, which is characterized by latency-associated transcripts, and from lytic VZV replication in skin. The chimeric nonobese diabetic severe combined immunodeficient mouse model may be useful for investigating other neurotropic human viruses.
Baiker
Armin
A
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Fabel
Klaus
K
Cozzio
Antonio
A
Zerboni
Leigh
L
Fabel
Konstanze
K
Sommer
Marvin
M
Uchida
Nobuko
N
He
Dongping
D
Weissman
Irving
I
Arvin
Ann M
AM
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D006562:Herpes Zoster / Q000378:metabolism*; D014645:Herpesvirus 3, Human / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000821:virology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D014183:Transplantation, Heterologous; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D014764:Viral Proteins