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Journal of Virology, June 2008, p. 5981-5985, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.00367-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Replication in a Superficial Epithelial Cell Niche Explains the Lack of Pathogenicity of Primate Foamy Virus Infections{triangledown}

Shannon M. Murray,1,2,{dagger} Louis J. Picker,3 Michael K. Axthelm,3 Kelly Hudkins,4 Charles E. Alpers,4 and Maxine L. Linial1,2*

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,1 Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington 98195,2 Oregon National Primate Research Center and Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, Oregon 97006,3 Department of Pathology, University of Washington, Seattle, Washington 981954

Received 19 February 2008/ Accepted 31 March 2008

Foamy viruses (FVs) are ancient retroviruses that are ubiquitous in nonhuman primates (NHPs). While FVs share many features with pathogenic retroviruses, such as human immunodeficiency virus, FV infections of their primate hosts have no apparent pathological consequences. Paradoxically, FV infections of many cell types in vitro are rapidly cytopathic. Previous work has shown that low levels of proviral DNA are found in most tissues of naturally infected rhesus macaques, but these proviruses are primarily latent. In contrast, viral RNA, indicative of viral replication, is restricted to tissues of the oral mucosa, where it is abundant. Here, we perform in situ hybridization on tissues from rhesus macaques naturally infected with simian FV (SFV). We show that superficial differentiated epithelial cells of the oral mucosa, many of which appear to be shedding from the tissue, are the major cell type in which SFV replicates. Thus, the innocuous nature of SFV infection can be explained by replication that is limited to differentiated superficial cells that are short-lived and shed into saliva. This finding can also explain the highly efficient transmission of FVs among NHPs.

* Corresponding author. Mailing address: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109. Phone: (206) 667-4442. Fax: (206) 667-5939. E-mail: mlinial{at}fhcrc.org

{triangledown} Published ahead of print on 9 April 2008.

{dagger} Present address: National Institutes of Health, Bethesda, MD 20892.

Journal of Virology, June 2008, p. 5981-5985, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.00367-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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