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Journal of Virology, May 1999, p. 3764-3777, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Host-Specific Modulation of the Selective Constraints Driving Human Immunodeficiency Virus Type 1 env Gene Evolution

Patrizia Bagnarelli,1,* Francesca Mazzola,1 Stefano Menzo,1 Maria Montroni,2 Luca Butini,2 and Massimo Clementi3

Institute of Microbiology1 and Laboratory of Clinical Immunology, Institute of Internal Medicine,2 University of Ancona, Ancona, and Department of Biomedical Sciences, University of Trieste, Trieste,3 Italy

Received 17 September 1998/Accepted 19 January 1999

To address the evolution of human immunodeficiency virus type 1 (HIV-1) within a single host, we analyzed the HIV-1 C2-V5 env regions of both cell-free genomic-RNA- and proviral-DNA-derived clones. Sequential samples were collected over a period of 3 years from six untreated subjects (three typical progressors [TPs] and three slow progressors [SPs], all with a comparable length of infection except one. The evolutionary analysis of the C2-V5 env sequences performed on 506 molecular clones (253 RNA- and 253 DNA-derived sequences) highlighted a series of differences between TPs and SPs. In particular, (i) clonal sequences from SPs (DNA and RNA) showed lower nucleotide similarity than those from TPs (P = 0.0001), (ii) DNA clones from SPs showed higher intra- and intersample nucleotide divergence than those from TPs (P < 0.05), (iii) higher host-selective pressure was generally detectable in SPs (DNA and RNA sequences), and (iv) the increase in the genetic distance of DNA and RNA sequences over time was paralleled by an increase in both synonymous (Ks) and nonsynonymous (Ka) substitutions in TPs but only in nonsynonymous substitutions in SPs. Several individual peculiarities of the HIV-1 evolutionary dynamics emerged when the V3, V4, and V5 env regions of both TPs and SPs were evaluated separately. These peculiarities, probably reflecting host-specific features of selective constraints and their continuous modulation, are documented by the dynamics of Ka/Ks ratios of hypervariable env domains.

* Corresponding author. Mailing address: Institute of Microbiology, University of Ancona, Via Pietro Ranieri, I-60100 Ancona, Italy. Phone: 39-71-5964849. Fax: 39-71-5964852. E-mail: bagnarelli{at}popcsi.unian.it.

Journal of Virology, May 1999, p. 3764-3777, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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