Estimating selection pressures on HIV-1 using phylogenetic likelihood models

• Published in: Statistics in medicine Vol. 27; no. 23; pp. 4779 - 4789
• Main Authors: Kosakovsky Pond, S. L., Poon, A. F. Y., Zárate, S., Smith, D. M., Little, S. J., Pillai, S. K., Ellis, R. J., Wong, J. K., Leigh Brown, A. J., Richman, D. D., Frost, S. D. W.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15.10.2008; Wiley Subscription Services, Inc
• Subjects: Amino acids; gag Gene Products, Human Immunodeficiency Virus - genetics; Genes; Genetics; HIV; HIV-1 - metabolism; HIV-1 - pathogenicity; Human immunodeficiency virus; Humans; Likelihood Functions; Medical statistics; Models, Statistical; Phylogeny; Selection, Genetic
• ISSN: 0277-6715; 1097-0258
• DOI: 10.1002/sim.3192

Human immunodeficiency virus (HIV‐1) can rapidly evolve due to selection pressures exerted by HIV‐specific immune responses, antiviral agents, and to allow the virus to establish infection in different compartments in the body. Statistical models applied to HIV‐1 sequence data can help to elucidate the nature of these selection pressures through comparisons of non‐synonymous (or amino acid changing) and synonymous (or amino acid preserving) substitution rates. These models also need to take into account the non‐independence of sequences due to their shared evolutionary history. We review how we have developed these methods and have applied them to characterize the evolution of HIV‐1 in vivo. To illustrate our methods, we present an analysis of compartment‐specific evolution of HIV‐1 env in blood and cerebrospinal fluid and of site‐to‐site variation in the gag gene of subtype C HIV‐1. Copyright © 2008 John Wiley & Sons, Ltd.