Document Detail


Insertion mutations in herpes simplex virus 1 glycoprotein H reduce cell surface expression, slow the rate of cell fusion, or abrogate functions in cell fusion and viral entry.
MedLine Citation:
PMID:  20007280     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Of the four required herpes simplex virus (HSV) entry glycoproteins, the precise role of gH-gL in fusion remains the most elusive. The heterodimer gH-gL has been proposed to mediate hemifusion after the interaction of another required glycoprotein, gD, with a receptor. To identify functional domains of HSV-1 gH, we generated 22 randomized linker-insertion mutants. Analyses of 22 gH mutants revealed that gH is relatively tolerant of insertion mutations, as 15 of 22 mutants permitted normal processing and transport of gH-gL to the cell surface. gH mutants that were not expressed well at the cell surface did not function in fusion or viral entry. The screening of gH mutants for function revealed the following: (i) for wild-type gH and some gH mutants, fusion with nectin-1-expressing target cells occurred more rapidly than with herpesvirus entry mediator (HVEM)-expressing target cells; (ii) some gH mutants reduced the rate of cell fusion without abrogating fusion completely, indicating that gH may play a role in governing the kinetics of fusion and may be responsible for a rate-limiting first stage in HSV-1 fusion; and (iii) only one gH mutant, located within the short cytoplasmic tail, completely abrogated function, indicating that the gH cytoplasmic tail is crucial for cell fusion and viral infectivity.
Authors:
Julia O Jackson; Erick Lin; Patricia G Spear; Richard Longnecker
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-12-09
Journal Detail:
Title:  Journal of virology     Volume:  84     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-25     Completed Date:  2010-02-18     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2038-46     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, the Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Ward 6-231, Chicago, IL 60611, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
COS Cells
Cercopithecus aethiops
Genetic Complementation Test
Herpesvirus 1, Human / genetics*,  pathogenicity,  physiology*
Humans
Kinetics
Mutagenesis, Insertional
Protein Structure, Tertiary
Receptors, Tumor Necrosis Factor, Member 14 / genetics,  physiology
Recombinant Proteins / chemistry,  genetics,  metabolism
Vero Cells
Viral Envelope Proteins / chemistry,  genetics*,  physiology*
Virus Internalization*
Grant Support
ID/Acronym/Agency:
CA021776/CA/NCI NIH HHS; CA117794/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Tumor Necrosis Factor, Member 14; 0/Recombinant Proteins; 0/TNFRSF14 protein, human; 0/Viral Envelope Proteins; 0/glycoprotein H, herpes simplex virus type 1
Comments/Corrections

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