Essential functions of the unique N-terminal region of the varicella-zoster virus glycoprotein E ectodomain in viral replication and in the pathogenesis of skin infection

Barbara Berarducci; Minako Ikoma; Shaye Stamatis; Marvin Sommer; Charles Grose; Ann M Arvin

doi:10.1128/JVI.00533-06

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Essential functions of the unique N-terminal region of the varicella-zoster virus glycoprotein E ectodomain in viral replication and in the pathogenesis of skin infection

Journal article

Open access

Peer reviewed

Essential functions of the unique N-terminal region of the varicella-zoster virus glycoprotein E ectodomain in viral replication and in the pathogenesis of skin infection

Barbara Berarducci, Minako Ikoma, Shaye Stamatis, Marvin Sommer, Charles Grose and Ann M Arvin

Journal of virology, Vol.80(19), pp.9481-9496

10/2006

DOI: 10.1128/JVI.00533-06

PMCID: PMC1617235

PMID: 16973553

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Abstract

Varicella-zoster virus (VZV) glycoprotein E (gE) is a multifunctional protein important for cell-cell spread, envelopment, and possibly entry. In contrast to other alphaherpesviruses, gE is essential for VZV replication. Interestingly, the N-terminal region of gE, comprised of amino acids 1 to 188, was shown not to be conserved in the other alphaherpesviruses by bioinformatics analysis. Mutational analysis was performed to investigate the functions associated with this unique gE N-terminal region. Linker insertions, serine-to-alanine mutations, and deletions were introduced in the gE N-terminal region in the VZV genome, and the effects of these mutations on virus replication and cell-cell spread, gE trafficking and localization, virion formation, and replication in vivo in the skin were analyzed. In summary, mutagenesis of the gE N-terminal region identified a new functional region in the VZV gE ectodomain essential for cell-cell spread and the pathogenesis of VZV skin tropism and demonstrated that different subdomains of the unique N-terminal region had specific roles in viral replication, cell-cell spread, and secondary envelopment.

Humans

Glycoproteins - metabolism

Molecular Sequence Data

Herpesvirus 3, Human - ultrastructure

Viral Proteins - metabolism

Skin Diseases, Infectious - metabolism

Glycoproteins - chemistry

Skin Diseases, Infectious - virology

Herpesvirus 3, Human - physiology

Glycoproteins - genetics

Amino Acid Sequence

Skin Diseases, Infectious - pathology

Viral Proteins - chemistry

Viral Proteins - genetics

Viral Proteins - ultrastructure

Mice, SCID

Microscopy, Electron

Mutation - genetics

Xenograft Model Antitumor Assays

Sequence Alignment

Animals

Virus Replication

Cell Line, Tumor

Herpesvirus 3, Human - pathogenicity

Mice

Kinetics

Glycoproteins - ultrastructure

Details

Title: Subtitle: Essential functions of the unique N-terminal region of the varicella-zoster virus glycoprotein E ectodomain in viral replication and in the pathogenesis of skin infection
Creators: Barbara Berarducci - Department of Pediatrics and Microbiology, Stanford University School of Medicine, 300 Pasteur Dr., Rm G312, Stanford, CA 94305-5208, USA. bbarbara@stanford.edu
Minako Ikoma
Shaye Stamatis
Marvin Sommer
Charles Grose
Ann M Arvin
Resource Type: Journal article
Publication Details: Journal of virology, Vol.80(19), pp.9481-9496
DOI: 10.1128/JVI.00533-06
PMID: 16973553
PMCID: PMC1617235
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Grant note: AI 22795 / NIAID NIH HHS R01 AI020459 / NIAID NIH HHS CA49605 / NCI NIH HHS R01 AI053846 / NIAID NIH HHS AI053846 / NIAID NIH HHS P01 CA049605 / NCI NIH HHS R01 AI022795 / NIAID NIH HHS AI20459 / NIAID NIH HHS
Language: English
Date published: 10/2006
Academic Unit: Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984093354902771

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