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Journal of Virology, March 2007, p. 2485-2496, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.01594-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Fitness Landscape of Human Immunodeficiency Virus Type 1 Protease Quasispecies{triangledown}

Guerau Fernàndez, Bonaventura Clotet, and Miguel Angel Martínez*

Fundacio irsiCaixa, Universitat Autònoma de Barcelona, Barcelona, Spain

Received 26 July 2006/ Accepted 29 November 2006

Here we show, at a high resolution (1%), the human immunodeficiency virus type 1 (HIV-1) protease gene quasispecies landscape from three infected naïve individuals. A huge range of genetic configurations was found (67%, 71%, and 80% of the nucleotide clones from the three individuals, respectively, were different), and these configurations created a dense net that linked different parts of the viral population. Similarly, a vast diversity of different protease activities was also found. Importantly, 65% of the analyzed enzymes had detectable protease activity, and 11% of the minority individual variants showed similar or better fitness than the master (most abundant) enzyme, suggesting that the viral complexity in this genomic region does not exclusively depend on the enzyme's catalytic efficiency. Several high-fitness minority variants had only one substitution compared to the master sequence, supporting the possibility that the rugged HIV-1 protease quasispecies fitness landscape may be formed by a continuous network that can be traversed by single mutational steps without passing through defective or less-adapted proteins.

* Correspondingauthor. Mailing address: Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain. Phone: 34-934656374. Fax: 34-934653968. E-mail: mmartinez{at}irsicaixa.es.

{triangledown} Published ahead of print on 6 December 2006.

Journal of Virology, March 2007, p. 2485-2496, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.01594-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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