J. Virol., 12 1996, 8879-8887, Vol 70, No. 12
Copyright © 1996, American Society for Microbiology

Intrapatient sequence variation of the gag gene of human immunodeficiency virus type 1 plasma virions

FK Yoshimura, K Diem, GH Learn Jr, S Riddell and L Corey
Department of Biological Structure, University of Washington, Seattle 98195, USA. fyoshi@med.wayne.edu

Because certain regions of the gag gene, such as p24, are highly conserved among human immunodeficiency virus (HIV) isolates, many therapeutic strategies have been directed at gag gene targets. Although intrapatient variation of segments of gag have been determined, little is known about the variability of the full-length gag gene for HIV isolated from a single individual. To evaluate intrapatient full-length gag variability, we derived the nucleotide sequences of at least 10 cDNA gag clones of virion RNA isolated from plasma for each of four asymptomatic HIV type 1-infected patients with relatively high CD4+ T- cell counts (300 to 450 cells per mm3). Mean values of intrapatient gag nucleotide variation obtained by pairwise comparisons ranged from 0.55 to 2.86%. For three subjects, this value was equivalent to that reported for intrapatient full-length env variation. The greatest range of intrapatient mean nucleotide variation for individual protein-coding regions was observed for p7. We did not detect any G-to-A hypermutation, as A-to-G and G-to-A transitions occurred at similar frequencies, accounting for 29 and 25%, respectively, of the changes. Mean variation values and phylogenetic analysis suggested that the extent of nucleotide variation correlated with the length of viral infection. Furthermore, no distinct subpopulations of quasispecies were detectable within an individual. The predicted amino acid sequences indicated that there were no regions within a gag protein that were comprised of clustered changes.

This article has been cited by other articles:

• del Alamo, M., Rivas, G., Mateu, M. G. (2005). Effect of Macromolecular Crowding Agents on Human Immunodeficiency Virus Type 1 Capsid Protein Assembly In Vitro. J. Virol. 79: 14271-14281 [Abstract] [Full Text]  
• Learn, G. H., Muthui, D., Brodie, S. J., Zhu, T., Diem, K., Mullins, J. I., Corey, L. (2002). Virus Population Homogenization following Acute Human Immunodeficiency Virus Type 1 Infection. J. Virol. 76: 11953-11959 [Abstract] [Full Text]  
• Peters, S., Munoz, M., Yerly, S., Sanchez-Merino, V., Lopez-Galindez, C., Perrin, L., Larder, B., Cmarko, D., Fakan, S., Meylan, P., Telenti, A. (2001). Resistance to Nucleoside Analog Reverse Transcriptase Inhibitors Mediated by Human Immunodeficiency Virus Type 1 p6 Protein. J. Virol. 75: 9644-9653 [Abstract] [Full Text]  
• Rouzine, I. M., Rodrigo, A., Coffin, J. M. (2001). Transition between Stochastic Evolution and Deterministic Evolution in the Presence of Selection: General Theory and Application to Virology. Microbiol. Mol. Biol. Rev. 65: 151-185 [Abstract] [Full Text]  
• Valentine, M. R., Termini, J. (2001). Kinetics of formation of hypoxanthine containing base pairs by HIV-RT: RNA template effects on the base substitution frequencies. Nucleic Acids Res 29: 1191-1199 [Abstract] [Full Text]  
• Rouzine, I. M., Coffin, J. M. (1999). Search for the Mechanism of Genetic Variation in the pro Gene of Human Immunodeficiency Virus. J. Virol. 73: 8167-8178 [Abstract] [Full Text]  
• Srivastava, M., Cartas, M., Rizvi, T. A., Singh, S. P., Serio, D., Kalyanaraman, V. S., Pollard, H. B., Srinivasan, A. (1999). HIV-1 Gag shares a signature motif with annexin (Anx7), which is required for virus replication. Proc. Natl. Acad. Sci. USA 96: 2704-2709 [Abstract] [Full Text]  
• Wei, Q., Fultz, P. N. (1998). Extensive Diversification of Human Immunodeficiency Virus Type 1 Subtype B Strains during Dual Infection of a Chimpanzee That Progressed to AIDS. J. Virol. 72: 3005-3017 [Abstract] [Full Text]