Imperial College London
Alternate

ProfessorPeterO'Hare

Faculty of Medicine, Department of Infectious Disease

Chair in Virology
 
 
 
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Contact

 

+44 (0)20 7594 9517p.ohare Website

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Abaitua:2011,
author = {Abaitua, F and Daikoku, T and Crump, CM and Bolstad, M and O'Hare, P},
journal = {J Virol},
pages = {2024--2036},
title = {A single mutation responsible for temperature sensitive entry and assembly defects in the VP1-2 protein of HSV},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21177812},
volume = {85},
year = {2011}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Evidence for an essential role of the HSV-1 tegument protein VP1-2 originated from the analysis of the temperature-sensitive mutant tsB7. At the non-permissive temperature (NPT), tsB7 capsids accumulate at the nuclear pore with defective genome release and substantially reduced virus gene expression. We compare the UL36 gene of tsB7 with the parental strain HFEM or strain 17 and identify four amino acid substitutions, 1061D>G, 1453Y>H, 2273Y>H and 2558T>I. We transferred the UL36 gene from tsB7, HFEM or strain 17, into a KOS background. While KOS recombinants containing the HFEM or strain 17 UL36 genes exhibited no ts defect, recombinants containing the tsB7 UL36 VP1-2, exhibited a 5-log deficiency at the NPT. Incubation at the NPT resulted in little or no virus gene expression though limited expression could be detected in a highly delayed fashion. Using shift-down regimes, gene expression recovered and recapitulated the time course normally observed, indicating that the initial block was in a reversible pathway. Using temperature shift-up regimes, a second defect later in the replication cycle was also observed in the KOS.ts viruses. We constructed a further series of recombinants which contained subsets of the 4 substitutions. A virus containing the w/t residue at position 1453 with the other three residues being from tsB7 VP1-2, exhibited w/t plaquing efficiency. Conversely a virus containing the three w/t residues but the single residue Y>H at position 1453 from tsB7, exhibited a 4-5 log drop in plaquing efficiency and was defective in at both early and late stages of infection.
AU  - Abaitua,F
AU  - Daikoku,T
AU  - Crump,CM
AU  - Bolstad,M
AU  - O'Hare,P
EP  - 2036
PY  - 2011///
SP  - 2024
TI  - A single mutation responsible for temperature sensitive entry and assembly defects in the VP1-2 protein of HSV
T2  - J Virol
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21177812
UR  - http://hdl.handle.net/10044/1/21223
VL  - 85
ER  -
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