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Journal of Virology, September 2008, p. 9023-9034, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00648-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Enzootic Nasal Tumor Virus Envelope Requires a Very Acidic pH for Fusion Activation and Infection{triangledown}

Marceline Côté, Thomas J. Kucharski, and Shan-Lu Liu*

Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 2B4, Canada

Received 23 March 2008/ Accepted 7 July 2008

Enzootic nasal tumor virus (ENTV) is a close relative of jaagsiekte sheep retrovirus (JSRV), and the two viruses use the same receptor, hyaluronidase 2 (Hyal2), for cell entry. We report here that, unlike the JSRV envelope (Env) protein, the ENTV Env protein does not induce cell fusion at pHs of 5.0 and above but requires a much lower pH (4.0 to 4.5) for fusion to occur. The entry of ENTV Env pseudovirions was substantially inhibited by bafilomycin A1 (BafA1) but was surprisingly enhanced by lysosomotropic agents and lysosomal protease inhibitors following a 4- to 6-h treatment period; of note, prolonged treatment with BafA1 or ammonium chloride completely blocked ENTV entry. Unlike typical pH-dependent viruses, ENTV Env pseudovirions were virtually resistant to inactivation at a low pH (4.5 or 5.0). Using chimeras formed from ENTV and JSRV Env proteins, we demonstrated that the transmembrane (TM) subunit of ENTV Env is primarily responsible for its unusually low pH requirement for fusion but found that the surface (SU) subunit of ENTV Env also critically influences its relatively low and pH-dependent fusion activity. Furthermore, the poor infectivity of ENTV pseudovirions in human cells was significantly improved by either replacing the SU subunit of ENTV Env with that of JSRV Env or overexpressing the functional Hyal2 receptor in target cells, suggesting that ENTV SU-Hyal2 interaction is likely to be the limiting step for viral infectivity. Collectively, our data reveal that the fusogenicity of ENTV Env is intrinsically lower than that of JSRV Env and that ENTV requires a more acidic pH for fusion, which may occur in an intracellular compartment(s) distinct from that used by JSRV.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 2B4, Canada. Phone: (514) 398-4582. Fax: (514) 398-7052. E-mail: shan-lu.liu{at}mcgill.ca

{triangledown} Published ahead of print on 16 July 2008.

Journal of Virology, September 2008, p. 9023-9034, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00648-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cote, M., Zheng, Y.-M., Liu, S.-L. (2009). Receptor Binding and Low pH Coactivate Oncogenic Retrovirus Envelope-Mediated Fusion. J. Virol. 83: 11447-11455 [Abstract] [Full Text]  


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