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Journal of Virology, October 1999, p. 8549-8558, Vol. 73, No. 10
Gene Therapy Center1 and
Departments of Pediatrics2 and
Molecular Genetics and Microbiology,3
University of Florida College of Medicine, Gainesville, Florida
32610, and Department of Pediatrics, Johns Hopkins
University School of Medicine, Baltimore, Maryland
212874
Received 6 April 1999/Accepted 18 June 1999
Latent infection with wild-type (wt) adeno-associated virus (AAV)
was studied in rhesus macaques, a species that is a natural host for
AAV and that has some homology to humans with respect to the preferred
locus for wt AAV integration. Each of eight animals was infected with
an inoculum of 1010 IU of wt AAV, administered by either
the intranasal, intramuscular, or intravenous route. Two additional
animals were infected intranasally with wt AAV and a helper adenovirus
(Ad), while one additional animal was inoculated with saline
intranasally as a control. There were no detectable clinical or
histopathologic responses to wt AAV administration. Molecular analyses,
including Southern blot, PCR, and fluorescence in situ hybridization,
were performed 21 days after infection. These studies indicated that
AAV DNA sequences persisted at the sites of administration, albeit at
low copy number, and in peripheral blood mononuclear cells.
Site-specific integration into the AAVS1-like locus was observed in a
subset of animals. All animals, except those infected by the intranasal
route with wt AAV alone, developed a humoral immune response to wt AAV
capsid proteins, as evidenced by a
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Latent Adeno-Associated Virus Infection Elicits
Humoral but Not Cell-Mediated Immune Responses in a Nonhuman
Primate Model
fourfold rise in anti-AAV
neutralizing titers. However, only animals infected with both wt AAV
and Ad developed cell-mediated immune responses to AAV capsid proteins. These findings provide some insights into the nature of anti-AAV immune
responses that may be useful in interpreting results of future
AAV-based gene transfer studies.
*
Corresponding author. Mailing address: University of
Florida Gene Therapy Center, Academic Research Bldg. Rm. R1-191, 1600 SW Archer Rd. (JHMHSC Box 100266), Gainesville, FL 32610-0266. Phone:
(352) 846-2739. Fax: (352) 846-2738. E-mail:
flotttr{at}peds.ufl.edu.
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