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Journal of Virology, July 2009, p. 6706-6716, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.02317-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Identification of a Feline Leukemia Virus Variant That Can Use THTR1, FLVCR1, and FLVCR2 for Infection{triangledown}

Zvi Shalev,1,2,{dagger} Simon P. Duffy,1,2,{dagger} Karen W. Adema,3 Rati Prasad,1,2 Naveen Hussain,1,2 Brian J. Willett,3 and Chetankumar S. Tailor1,2*

Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada,1 Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5G, Canada,2 Retrovirus Research Laboratory, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, United Kingdom3

Received 5 November 2008/ Accepted 3 April 2009

The pathogenic subgroup C feline leukemia virus (FeLV-C) arises in infected cats as a result of mutations in the envelope (Env) of the subgroup A FeLV (FeLV-A). To better understand emergence of FeLV-C and potential FeLV intermediates that may arise, we characterized FeLV Env sequences from the primary FY981 FeLV isolate previously derived from an anemic cat. Here, we report the characterization of the novel FY981 FeLV Env that is highly related to FeLV-A Env but whose variable region A (VRA) receptor recognition sequence partially resembles the VRA sequence from the prototypical FeLV-C/Sarma Env. Pseudotype viruses bearing FY981 Env were capable of infecting feline, human, and guinea pig cells, suggestive of a subgroup C phenotype, but also infected porcine ST-IOWA cells that are normally resistant to FeLV-C and to FeLV-A. Analysis of the host receptor used by FY981 suggests that FY981 can use both the FeLV-C receptor FLVCR1 and the feline FeLV-A receptor THTR1 for infection. However, our results suggest that FY981 infection of ST-IOWA cells is not mediated by the porcine homologue of FLVCR1 and THTR1 but by an alternative receptor, which we have now identified as the FLVCR1-related protein FLVCR2. Together, our results suggest that FY981 FeLV uses FLVCR1, FLVCR2, and THTR1 as receptors. Our findings suggest the possibility that pathogenic FeLV-C arises in FeLV-infected cats through intermediates that are multitropic in their receptor use.

* Corresponding author. Mailing address: The Hospital for Sick Children, Program in Cell Biology, Room 7129 Elm Wing, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Phone: (416) 813 6429. Fax: (416) 813 5993. E-mail: chetankumar.tailor{at}sickkids.ca

{triangledown} Published ahead of print on 15 April 2009.

{dagger} These authors contributed equally to the work.

Journal of Virology, July 2009, p. 6706-6716, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.02317-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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