Document Detail


Retroviral mutation rates and A-to-G hypermutations during different stages of retroviral replication.
MedLine Citation:
PMID:  8892879     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Retroviruses mutate at a high rate in vivo during viral replication. Mutations may occur during proviral transcription by RNA polymerase II, during minus-strand DNA synthesis (RNA template) by viral reverse transcriptase, or during plus-strand DNA synthesis (DNA template) by reverse transcriptase. To determine the contributions of different stages of replication to the retroviral mutation rates, we developed a spleen necrosis virus-based in vivo system to selectively identify mutations occurring during the early stage (RNA transcription plus minus-strand synthesis) and the late stage (plus-strand synthesis plus DNA repair). A lacZalpha reporter gene was inserted into the long terminal repeat (LTR) of a spleen necrosis virus shuttle vector, and proviruses were recovered from infected cells as plasmids containing either one or both LTRs. Plasmids containing both LTRs generated a mutant phenotype only if the lacZalpha genes in both LTRs were mutated, which is most likely to occur during the early stage. Mutant phenotypes were identified from plasmids containing one LTR regardless of the stage at which the mutations occurred. Thus, mutant frequencies obtained after recovery of plasmids containing both LTRs or one LTR provided early-stage and total mutation rates, respectively. Analysis of 56,409 proviruses suggested that the retroviral mutation rates during the early and late stages of replication were equal or within twofold of each other. In addition, two mutants with A-to-G hypermutations were discovered, suggesting a role for mammalian double-stranded RNA adenosine deaminase enzyme in retroviral mutations. These experiments provide a system to selectively identify mutations in the early stage of retroviral replication and to provide upper and lower limits to the in vivo mutation rates during minus-strand and plus-strand synthesis, respectively.
Authors:
T Kim; R A Mudry; C A Rexrode; V K Pathak
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  70     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1996-12-30     Completed Date:  1996-12-30     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7594-602     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Mary Babb Randolph Cancer Center, West Virginia University, Morgantown 26506, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
DNA, Viral
Deoxyribonuclease BamHI / metabolism
Deoxyribonuclease HindIII / metabolism
Dogs
Gammaretrovirus / genetics*,  physiology
Gene Deletion
Lac Operon*
Molecular Sequence Data
Multigene Family
Mutagenesis, Insertional
Mutation
Proviruses / genetics
Tumor Cells, Cultured
Virus Replication
Grant Support
ID/Acronym/Agency:
CA58875/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Viral; EC 3.1.21.-/Deoxyribonuclease BamHI; EC 3.1.21.-/Deoxyribonuclease HindIII
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