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Journal of Virology, November 2001, p. 10446-10454, Vol. 75, No. 21
Department of Microbiology and Immunology,
Center for Gene Therapy and Comprehensive Cancer Center, University
of Michigan Medical School, Ann Arbor, Michigan 48109-0942
Received 21 June 2001/Accepted 6 August 2001
Although it has been demonstrated that the adenovirus IVa2 protein
binds to the packaging domains on the viral chromosome and interacts
with the viral L1 52/55-kDa protein, which is required for viral DNA
packaging, there has been no direct evidence demonstrating that the
IVa2 protein is involved in DNA packaging. To understand in greater
detail the DNA packaging mechanisms of adenovirus, we have asked
whether DNA packaging is serotype or subgroup specific. We found that
Ad7 (subgroup B), Ad12 (subgroup A), and Ad17 (subgroup D) cannot
complement the defect of an Ad5 (subgroup C) mutant, pm8001, which does not package its DNA due to a mutation
in the L1 52/55-kDa gene. This indicates that the DNA packaging systems of different serotypes cannot interact productively with Ad5 DNA. Based
on this, a chimeric virus containing the Ad7 genome except for the
inverted terminal repeats and packaging sequence from Ad5 was
constructed. This chimeric virus replicates its DNA and synthesizes Ad7
proteins, but it cannot package its DNA in 293 cells or 293 cells
expressing the Ad5 L1 52/55-kDa protein. However, this chimeric virus
packages its DNA in 293 cells expressing the Ad5 IVa2 protein. These
results indicate that the IVa2 protein plays a role in viral DNA
packaging and that its function is serotype specific. Since this
chimeric virus cannot package its own DNA, but produces all the
components for packaging Ad7 DNA, it may be a more suitable helper
virus for the growth of Ad7 gutted vectors for gene transfer.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.21.10446-10454.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Role for the Adenovirus IVa2 Protein in Packaging of Viral
DNA
*
Corresponding author. Mailing address: University of
Michigan Medical School, 1500 E. Medical Center Dr., 6310 Cancer
Center, Ann Arbor, MI 48109-0942. Phone: (734) 763-9162. Fax: (734)
615-6560. E-mail: imperial{at}umich.edu.
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