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Journal of Virology, March 2009, p. 2623-2631, Vol. 83, No. 6
0022-538X/09/$08.00+0     doi:10.1128/JVI.02160-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Host Immune Responses to Chronic Adenovirus Infections in Human and Nonhuman Primates {triangledown} ,{dagger}

Roberto Calcedo, Luk H. Vandenberghe, Soumitra Roy, Suryanarayan Somanathan, Lili Wang, and James M. Wilson*

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Received 13 October 2008/ Accepted 22 December 2008

Recent studies indicate that great apes and macaques chronically shed adenoviruses in the stool. Shedding of adenovirus in the stool of humans is less prevalent, although virus genomes persist in gut-associated lymphoid tissue in the majority of individual samples. Chimpanzees have high levels of broadly reactive neutralizing antibodies to adenoviruses in serum, with very low frequencies of adenovirus-specific T cells in peripheral blood. A similar situation exists in macaques; sampling of guts from macaques demonstrated adenovirus-specific T cells in lamina propria. Humans show intermediate levels of serum neutralizing antibodies, with adenovirus-specific T cells in peripheral blood of all individuals sampled and about 20% of samples from the gut, suggesting a potential role of T cells in better controlling virus replication in the gut. The overall structure of the E3 locus, which is involved in modulating the host's response to infection, is degenerate in humans compared to that in apes, which may contribute to diminished evasion of host immunity. The impact of adenovirus persistence and immune responses should be considered when using adenoviral vectors in gene therapy and genetic vaccines.

* Corresponding author. Mailing address: Gene Therapy Program, University of Pennsylvania, Suite 2000 TRL, 125 S. 31st Street, Philadelphia, PA 19104. Phone: (215) 898-0226. Fax: (215) 898-6588. E-mail: wilsonjm{at}mail.med.upenn.edu

{triangledown} Published ahead of print on 30 December 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, March 2009, p. 2623-2631, Vol. 83, No. 6
0022-538X/09/$08.00+0     doi:10.1128/JVI.02160-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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