Fowl Adenovirus 4 (FAdV-4)-Based Infectious Clone for Vaccine Vector Development and Viral Gene Function Studies
Fowl adenovirus 4 (FAdV-4) is associated with economically important poultry diseases. Recent studies of fully sequenced genomes of FAdV-4 isolates suggest potential genomic regions associated with virulence and amenable for manipulation and vector development. Direct manipulation of viral genomes i...
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doaj-c218a0265092449d8a48280b6b33a09c2020-11-24T23:00:51ZengMDPI AGViruses1999-49152018-02-011029710.3390/v10020097v10020097Fowl Adenovirus 4 (FAdV-4)-Based Infectious Clone for Vaccine Vector Development and Viral Gene Function StudiesYanlong Pei0Juan C. Corredor1Bryan D. Griffin2Peter J. Krell3Éva Nagy4Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaFowl adenovirus 4 (FAdV-4) is associated with economically important poultry diseases. Recent studies of fully sequenced genomes of FAdV-4 isolates suggest potential genomic regions associated with virulence and amenable for manipulation and vector development. Direct manipulation of viral genomes is cumbersome, as opposed to that of infectious clones—viral genomes cloned into plasmid or cosmid vectors. In this work, we generated an infectious clone, pFAdV-4 ON1, containing the entire viral genome of a nonpathogenic FAdV-4 (ON1 isolate). pFAdV-4 ON1 was used for targeted deletion of open reading frames (ORFs) 16 and 17 and replacement with the enhanced green fluorescence protein (EGFP) expression cassette to generate recombinant viruses. These viruses were viable, and EGFP was expressed in infected cells. Their replication, however, was significantly reduced with respect to that of the wild-type virus. These observations suggest the potential utility of FAdV-4 as a vaccine vector and the importance of ORFs 16 and 17 for virus replication at wild-type levels. To our knowledge, this is the first report of an infectious clone based on the FAdV-4 genome, and our results demonstrate its utility for studies of virulence determinants and as a platform for either vaccine or gene delivery vectors.http://www.mdpi.com/1999-4915/10/2/97fowl adenovirus 4 ON1infectious cloneORF16 and ORF17enhanced green fluorescence proteinrecombinant vaccine vectorFAdmid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yanlong Pei Juan C. Corredor Bryan D. Griffin Peter J. Krell Éva Nagy |
spellingShingle |
Yanlong Pei Juan C. Corredor Bryan D. Griffin Peter J. Krell Éva Nagy Fowl Adenovirus 4 (FAdV-4)-Based Infectious Clone for Vaccine Vector Development and Viral Gene Function Studies Viruses fowl adenovirus 4 ON1 infectious clone ORF16 and ORF17 enhanced green fluorescence protein recombinant vaccine vector FAdmid |
author_facet |
Yanlong Pei Juan C. Corredor Bryan D. Griffin Peter J. Krell Éva Nagy |
author_sort |
Yanlong Pei |
title |
Fowl Adenovirus 4 (FAdV-4)-Based Infectious Clone for Vaccine Vector Development and Viral Gene Function Studies |
title_short |
Fowl Adenovirus 4 (FAdV-4)-Based Infectious Clone for Vaccine Vector Development and Viral Gene Function Studies |
title_full |
Fowl Adenovirus 4 (FAdV-4)-Based Infectious Clone for Vaccine Vector Development and Viral Gene Function Studies |
title_fullStr |
Fowl Adenovirus 4 (FAdV-4)-Based Infectious Clone for Vaccine Vector Development and Viral Gene Function Studies |
title_full_unstemmed |
Fowl Adenovirus 4 (FAdV-4)-Based Infectious Clone for Vaccine Vector Development and Viral Gene Function Studies |
title_sort |
fowl adenovirus 4 (fadv-4)-based infectious clone for vaccine vector development and viral gene function studies |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2018-02-01 |
description |
Fowl adenovirus 4 (FAdV-4) is associated with economically important poultry diseases. Recent studies of fully sequenced genomes of FAdV-4 isolates suggest potential genomic regions associated with virulence and amenable for manipulation and vector development. Direct manipulation of viral genomes is cumbersome, as opposed to that of infectious clones—viral genomes cloned into plasmid or cosmid vectors. In this work, we generated an infectious clone, pFAdV-4 ON1, containing the entire viral genome of a nonpathogenic FAdV-4 (ON1 isolate). pFAdV-4 ON1 was used for targeted deletion of open reading frames (ORFs) 16 and 17 and replacement with the enhanced green fluorescence protein (EGFP) expression cassette to generate recombinant viruses. These viruses were viable, and EGFP was expressed in infected cells. Their replication, however, was significantly reduced with respect to that of the wild-type virus. These observations suggest the potential utility of FAdV-4 as a vaccine vector and the importance of ORFs 16 and 17 for virus replication at wild-type levels. To our knowledge, this is the first report of an infectious clone based on the FAdV-4 genome, and our results demonstrate its utility for studies of virulence determinants and as a platform for either vaccine or gene delivery vectors. |
topic |
fowl adenovirus 4 ON1 infectious clone ORF16 and ORF17 enhanced green fluorescence protein recombinant vaccine vector FAdmid |
url |
http://www.mdpi.com/1999-4915/10/2/97 |
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