Adeno-associated Viruses Undergo Substantial Evolution in Primates During Natural Infections

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Apr 30

PMID 12716974

Citations 165

Authors

Guangping Gao

Mauricio R Alvira

Suryanarayan Somanathan

You Lu

Luk H Vandenberghe

John J Rux

Roberto Calcedo

Julio Sanmiguel

Zahra Abbas

James M Wilson

Affiliations

Soon will be listed here.

Abstract

Adeno-associated viruses (AAVs) are single-stranded DNA viruses that are endemic in human populations without known clinical sequelae and are being evaluated as vectors for human gene therapy. To better understand the biology of this virus, we examined a number of nonhuman primate species for the presence of previously uncharacterized AAVs and characterized their structure and distribution. AAV genomes were widely disseminated throughout multiple tissues of a variety of nonhuman primate species. Surprising diversity of sequence, primarily localized to hypervariable regions of the capsid protein, was detected. This diversity of sequence is caused, in part, by homologous recombination of co-infecting parental viruses that modify the serologic reactivity and tropism of the virus. This is an example of rapid molecular evolution of a DNA virus in a way that was formerly thought to be restricted to RNA viruses.

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