Document Detail


Bovine leukemia virus structural gene vectors are immunogenic and lack pathogenicity in a rabbit model.
MedLine Citation:
PMID:  10482566     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Infection with a replication-competent bovine leukemia virus structural gene vector (BLV SGV) is an innovative vaccination approach to prevent disease by complex retroviruses. Previously we developed BLV SGV that constitutively expresses BLV gag, pol, and env and related cis-acting sequences but lacks tax, rex, RIII, and GIV and most of the BLV long terminal repeat sequences, including the cis-acting Tax and Rex response elements. The novel SGV virus is replication competent and replicates a selectable vector to a titer similar to that of the parental BLV in cell culture. The overall goal of this study was to test the hypothesis that infection with BLV SGV is nonpathogenic in rabbits. BLV infection of rabbits by inoculation of cell-free BLV or cell-associated BLV typically causes an immunodeficiency-like syndrome and death by 1 year postinfection. We sought to evaluate whether in vivo transfection of BLV provirus recapitulates pathogenic BLV infection and to compare BLV and BLV SGV with respect to infection, immunogenicity, and clinical outcome. Three groups of rabbits were subjected to in vivo transfection with BLV, BLV SGV, or negative control DNA. The results of our 20-month study indicate that in vivo transfection of rabbits with BLV recapitulates the fatal BLV infection produced by cell-free or cell-associated BLV. The BLV-infected rabbits exhibited sudden onset of clinical decline and immunodeficiency-like symptoms that culminated in death. BLV and BLV SGV infected peripheral blood mononuclear cells and induced similar levels of seroconversion to BLV structural proteins. However, BLV SGV exhibited a reduced proviral load and did not trigger the immunodeficiency-like syndrome. These results are consistent with the hypothesis that BLV SGV is infectious and immunogenic and lacks BLV pathogenicity in rabbits, and they support the use of this modified proviral vector delivery system for vaccines against complex retroviruses like BLV.
Authors:
L Kucerova; V Altanerova; C Altaner; K Boris-Lawrie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  73     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-10-12     Completed Date:  1999-10-12     Revised Date:  2013-09-23    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  8160-6     Citation Subset:  IM; X    
Affiliation:
Cancer Research Institute, Slovak Academy of Sciences, SK-833 91 Bratislava, Slovakia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cattle
Enzootic Bovine Leukosis / immunology,  prevention & control*
Genes, Viral*
Leukemia Virus, Bovine / genetics*,  immunology*
Rabbits
Viral Structural Proteins / genetics*,  immunology*
Viral Vaccines* / genetics,  immunology
Grant Support
ID/Acronym/Agency:
AI40851/AI/NIAID NIH HHS; P30CA16058/CA/NCI NIH HHS; R03 TW001217/TW/FIC NIH HHS
Chemical
Reg. No./Substance:
0/Viral Structural Proteins; 0/Viral Vaccines
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