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.
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.
Berarducci
Barbara
B
Department of Pediatrics and Microbiology, Stanford University School of Medicine, 300 Pasteur Dr., Rm G312, Stanford, CA 94305-5208, USA. bbarbara@stanford.edu
Ikoma
Minako
M
Stamatis
Shaye
S
Sommer
Marvin
M
Grose
Charles
C
Arvin
Ann M
AM
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D014645:Herpesvirus 3, Human / Q000472:pathogenicity* / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D007700:Kinetics; D051379:Mice; D016513:Mice, SCID; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016415:Sequence Alignment; D012874:Skin Diseases, Infectious / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
D006023:Glycoproteins; D014764:Viral Proteins