Synonymous substitution rates predict HIV disease progression as a result of underlying replication dynamics. — Peter Medawar Building for Pathogen Research Cookies on this website We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings. Accept all cookies Reject all non-essential cookies Site Map Accessibility Contact Cookies Log in Home About us Sir Peter Medawar Find us Contact us Jobs and Vacancies Latest news and events Shared Cytometry Facility Research Dphil Studentships DPhil Project Funding Programs Medawar Courses Graduate Studies Seminars Our team Funding Bodies Intranet COVID and Returning to Work Weekly WiP Contacts Research checklist Resources Policies New to Oxford Search Publications Synonymous substitution rates predict HIV disease progression as a result of underlying replication dynamics. Synonymous substitution rates predict HIV disease progression as a result of underlying replication dynamics. Lemey P., Kosakovsky Pond SL., Drummond AJ., Pybus OG., Shapiro B., Barroso H., Taveira N., Rambaut A. Upon HIV transmission, some patients develop AIDS in only a few months, while others remain disease free for 20 or more years. This variation in the rate of disease progression is poorly understood and has been attributed to host genetics, host immune responses, co-infection, viral genetics, and adaptation. Here, we develop a new "relaxed-clock" phylogenetic method to estimate absolute rates of synonymous and nonsynonymous substitution through time. We identify an unexpected association between the synonymous substitution rate of HIV and disease progression parameters. Since immune activation is the major determinant of HIV disease progression, we propose that this process can also determine viral generation times, by creating favourable conditions for HIV replication. These conclusions may apply more generally to HIV evolution, since we also observed an overall low synonymous substitution rate for HIV-2, which is known to be less pathogenic than HIV-1 and capable of tempering the detrimental effects of immune activation. Humoral immune responses, on the other hand, are the major determinant of nonsynonymous rate changes through time in the envelope gene, and our relaxed-clock estimates support a decrease in selective pressure as a consequence of immune system collapse. Original publication DOI 10.1371/journal.pcbi.0030029 Type Journal article Journal PLoS Comput Biol Publication Date 16/02/2007 Volume 3 Keywords Amino Acid Sequence, Amino Acid Substitution, Codon, Computer Simulation, DNA Mutational Analysis, Disease Progression, Evolution, Molecular, Genetic Predisposition to Disease, Genetic Variation, HIV Infections, Humans, Models, Genetic, Molecular Sequence Data, Viral Envelope Proteins, Virus Activation, Virus Replication © 2022 The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, OX1 3SY, United Kingdom Freedom of Information Privacy Policy Data Collected on this Website Copyright Accessibility Statement Medical Sciences Division Oxford University Some images courtesy of NHGRIZ Site Map Accessibility Contact Cookies Log in Welcome About us Sir Peter Medawar Find us Jobs and Vacancies Latest news and events Shared Cytometry Facility Research Research Home COVID Research NDM Research Groups Barnes Group Dunachie Group Frater Group Goulder Group Klenerman Group Matthews Group Simmonds Group Wheeler Group Tropical Medicine Research Groups Ariana Group English Group Marsh (Kevin) Group Wills Group Dunachie Group Zoology Research Groups Faria Group Gupta Group Katzourakis Group Lourenço Group Maiden Group McLean Group Pybus Group Smith Group Dphil Studentships DPhil Project Funding Programs Medawar Courses Medawar Courses Graduate Studies Graduate Studies Seminars Seminars Our team Funding Bodies Funding Bodies Intranet COVID and Returning to Work Weekly WiP Key contacts Research checklist Resources Policies University Policies Out of Hours Working Fire Safety Bomb Threat Information security - Data breach Confidential waste New to Oxford