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Journal of Virology, June 2008, p. 5429-5439, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02462-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Restriction of Foamy Viruses by Primate Trim5{alpha}{triangledown}

Melvyn W. Yap,1,{dagger} Dirk Lindemann,2,{dagger} Nicole Stanke,2 Juliane Reh,2 Dana Westphal,2 Helmut Hanenberg,3,4 Sadayuki Ohkura,1 and Jonathan P. Stoye1*

Division of Virology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom,1 Institute of Virology, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany,2 Department of Pediatric Oncology, Hematology & Clinical Immunology, Children's Hospital, Heinrich Heine University, Moorenstr. 5, 40225 Düsseldorf, Germany,3 Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Riley Hospital for Children, Indiana University School of Medicine, 1044 W. Walnut Street, Indianapolis, Indiana 462024

Received 15 November 2007/ Accepted 19 March 2008

Foamy viruses (FVs) are unconventional retroviruses with a replication strategy that is significantly different from orthoretroviruses and bears some homology to that of hepadnaviruses. Although some cellular proteins, such as APOBEC3, have been reported to block FVs, no restriction by Trim5{alpha} has been described to date. The sensitivity of three FV isolates of human-chimpanzee or prototypic (PFV), macaque (SFVmac), and feline (FFV) origin to a variety of primate Trim5{alpha}s was therefore tested. PFV and SFVmac were restricted by Trim5{alpha}s from most New World monkeys, but not from other primates, whereas FFV-based vectors were restricted by Trim5{alpha}s from the great apes gorilla and orangutan. Trim5{alpha}s from Old World monkeys did not restrict any FV isolate tested. Capuchin Trim5{alpha} was unique, as it restricted SFVmac and FFV but not PFV. Trim5{alpha} specificity for FVs was determined by the B30.2 domain, interestingly involving, in some instances, the same residues of the variable regions previously implicated as major determinants for human immunodeficiency virus type 1 restriction. FVs with chimeric Gags were made to map the viral determinants of sensitivity to restriction. The N-terminal half of the Gag molecule was found to contain the regions that control susceptibility. This region most likely corresponds to the capsid of conventional retroviruses. Due to their unique replication strategy, FVs should provide a valuable new system to examine the mechanism of retroviral restriction by Trim5{alpha}.

* Corresponding author. Mailing address: Medical Research Council, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44 20 88162140. Fax: 44 20 89064477. E-mail: jstoye{at}nimr.mrc.ac.uk

{triangledown} Published ahead of print on 26 March 2008.

{dagger} M.W.Y. and D.L. contributed equally to this study.

Journal of Virology, June 2008, p. 5429-5439, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02462-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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