Document Detail


Characterization of the expression and immunogenicity of poliovirus replicons that encode simian immunodeficiency virus SIVmac239 Gag or envelope SU proteins.
MedLine Citation:
PMID:  8989427     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effectiveness of the poliovirus vaccines to induce both systemic and mucosal immunity has prompted the development of this virus as a vector in which to express foreign proteins. Our laboratory has previously reported on the construction and characterization of poliovirus genomes that encode HIV-1 proteins (Porter DC, et al.: J Virol 1996;70:2643-2649). To develop this system further, we have constructed poliovirus genomes, referred to as replicons, which encode the SIVmac239 Gag or Env SU in place of the poliovirus capsid gene (P1). Since the replicons do not encode capsid proteins, they are encapsidated into poliovirus by passage with a recombinant vaccinia virus, VVP1, which provides the poliovirus capsid proteins in trans. Using this system, we have derived stocks of the encapsidated replicons which encode the SIVmac239 or Env SU protein. Infection of cells with the replicon that encodes SIVmac239 Gag resulted in the expression of a 55-kDa protein that was released from the infected cells. Analysis of the sedimentation of the released proteins by sucrose density gradient centrifugation revealed that the protein was released from the cell in the form of a virus-like particle. Infection of cells with the replicons encoding the SIVmac239 Env SU resulted in the expression of a 63-kDa protein, corresponding to the molecular mass predicted for the nonglycosylated SIVmac239 SU protein. A second protein with a molecular mass greater than 160 kDa was also immunoprecipitated. After enzymatic deglycosylation, this protein migrated at a molecular mass consistent with that for an Env SU dimer. Analysis of the medium from cells infected with the replicon encoding SIVmac239 Env SU revealed the presence of a protein of molecular mass 85-90 kDa, possibly representing a fragment of the SIVmac239 or Env SU protein. To determine the immunogenicity of the replicons encoding SIVmac239 Gag or Env SU, transgenic mice that express the human receptor for poliovirus, and are thus susceptible to poliovirus, were immunized via the intramuscular route. A serum antibody response to SIV envelope was detected following booster immunization, establishing that the encapsidated replicon was immunogenic. Finally, we demonstrate that the replicons have the capacity to infect peripheral blood mononuclear monocytes/macrophages, suggesting that this cell is a possible target for in vivo infection. The results of our studies, then, lend further support for the development and application of recombinant poliovirus replicons in a vaccine strategy.
Authors:
M J Anderson; D C Porter; Z Moldoveanu; T M Fletcher; S McPherson; C D Morrow
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  13     ISSN:  0889-2229     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-03-19     Completed Date:  1997-03-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  53-62     Citation Subset:  IM; X    
Affiliation:
Department of Microbiology, University of Alabama at Birmingham 35294, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Gene Expression
Gene Products, env / chemistry,  genetics,  immunology*
Gene Products, gag / chemistry,  genetics,  immunology*
Genes, env
Genes, gag
Humans
Macaca nemestrina
Macrophages, Peritoneal / virology
Membrane Proteins*
Mice
Mice, Transgenic
Molecular Weight
Poliovirus / genetics*
Receptors, Virus
Replicon / genetics
Simian immunodeficiency virus / genetics,  immunology*
Vaccination
Vaccinia virus / genetics
Viral Vaccines / genetics,  immunology*
Virion
Grant Support
ID/Acronym/Agency:
AI27767/AI/NIAID NIH HHS; AI28147/AI/NIAID NIH HHS; T32-AI 07150/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Gene Products, env; 0/Gene Products, gag; 0/Membrane Proteins; 0/Receptors, Virus; 0/Viral Vaccines; 0/poliovirus receptor

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