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Journal of Virology, May 2000, p. 4839-4852, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Rev-Independent Human Immunodeficiency Virus Type 1 (HIV-1)-Based Vector That Exploits a Codon-Optimized HIV-1 gag-pol Gene

Ekaterini Kotsopoulou,1 V. Narry Kim,1 Alan J. Kingsman,1,2 Susan M. Kingsman,1,2,* and Kyriacos A. Mitrophanous2

Retrovirus Molecular Biology Group, Department of Biochemistry, University of Oxford, Oxford OX1 3QU,1 and Oxford BioMedica (UK) Ltd., Oxford OX4 4GA,2 United Kingdom

Received 29 July 1999/Accepted 15 February 2000

The human immunodeficiency virus (HIV) genome is AU rich, and this imparts a codon bias that is quite different from the one used by human genes. The codon usage is particularly marked for the gag, pol, and env genes. Interestingly, the expression of these genes is dependent on the presence of the Rev/Rev-responsive element (RRE) regulatory system, even in contexts other than the HIV genome. The Rev dependency has been explained in part by the presence of RNA instability sequences residing in these coding regions. The requirement for Rev also places a limitation on the development of HIV-based vectors, because of the requirement to provide an accessory factor. We have now synthesized a complete codon-optimized HIV-1 gag-pol gene. We show that expression levels are high and that expression is Rev independent. This effect is due to an increase in the amount of gag-pol mRNA. Provision of the RRE in cis did not lower protein or RNA levels or stimulate a Rev response. Furthermore we have used this synthetic gag-pol gene to produce HIV vectors that now lack all of the accessory proteins. These vectors should now be safer than murine leukemia virus-based vectors.

* Corresponding author. Mailing address: Oxford BioMedica (UK) Ltd., Medawar Center, Oxford Science Park, Oxford OX4 4GA, United Kingdom. Phone: (0) 1865-783000. Fax: (0) 1865-783001. E-mail: s.kingsman{at}oxfordbiomedica.co.uk.

Journal of Virology, May 2000, p. 4839-4852, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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