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Journal of Virology, May 2005, p. 6459-6471, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6459-6471.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Functional Chimeras of Human Immunodeficiency Virus Type 1 gp120 and Influenza A Virus (H3) Hemagglutinin

K. M. Copeland, A. J. Elliot,{dagger} and R. S. Daniels*

Division of Virology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom

Received 2 September 2004/ Accepted 4 October 2004

In an attempt to produce a protein that will allow determination of the native human immunodeficiency virus type 1 (HIV-1) gp120 (Env) structure in its trimeric state, we fused the globular head of gp120 to the stalk region of influenza virus A (X31) hemagglutinin (HA). The chimeric protein (EnvHA) has been expressed by using a recombinant vaccinia virus system, and its functional characteristics were determined. EnvHA is expressed as a 120- to 150-kDa protein that can oligomerize to form dimers and trimers. It retains the low-pH (5.2 to 5.4) requirement of X31-HA to trigger membrane fusion but, unlike X31-HA, it is not absolutely dependent on exogenously added trypsin for protein processing to release the HA2 fusion peptide. In terms of receptor binding the chimeric protein retains specificity for human CD4 but, in relation to the membrane fusion event, it appears to lose the Env coreceptor specificity of the parental HIV-1 strains: NL43 for CXCR4 and JRFL for CCR5. These properties suggest that stable, functional EnvHAs are being produced and that they may be exploited in terms of structural studies. Further, the potential of introducing the envHA genes into influenza viruses, by use of reverse genetics, and their use as a therapeutic vaccine for HIV are discussed.


* Corresponding author. Mailing address: Division of Virology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44 (0) 20-8816-2139. Fax: 44 (0) 20-8906-4477. E-mail: rdaniel{at}nimr.mrc.ac.uk.

{dagger} Present address: Birmingham Research Unit of the Royal College of General Practitioners, Lordswood House, 54 Lordswood Rd., Harborne, Birmingham B17 9DB, United Kingdom.


Journal of Virology, May 2005, p. 6459-6471, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6459-6471.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.