|Title / Titel||The rate paradox in HIV evolution:
Resolving the discrepancy between the within and between patients rates of evolution of HIV-1
|Abstract (PDF, 14 KB)|
|Summary / Zusammenfassung||Background: One key empirical paradox challenging our understanding of HIV evolutionary biology is the vast difference in the estimated rates of HIV evolution when computed within and between patients. At the level of within-patient evolution, the estimated rate of evolution for the variable regions of the envelope gene often lie around 1% per year (DRUMMOND et al. 2002; JOOS et al. 2008; SHANKARAPPA et al. 1999). At the between-patient level, the estimated rate of evolution is often much lower, around 0.2% per year (KORBER et al. 2000; LEMEY et al. 2006). However, these estimates were obtained from different data and are therefore hard to compare.
Study Aims: Using data from the Swiss HIV Cohort Study (SHCS), we will quantify the rate of evolution within patients and the rate of evolution between patients. We will estimate an overall rate of within-patient and between-patient evolution and additionally estimate individual rates for the different transmission groups (MSMs, HETs, IDUs).
Quantifying the evolutionary rate difference within a patient and between a patient and assessing weather there is a significant difference between transmission groups allows to disentangle different scenarios that might be responsible for certain particularities in the HIV tree. Such scenarios might be:
1) Selective transmission from compartments or sites with low turnover rate.
2) Only archived viruses are transmitted.
3) Only transmission in the acute phase of an HIV infection.
4) Predominant transmission from super-spreaders.
5) Infection by multiple versus single strains
Study Design: BEAST (DRUMMOND and RAMBAUT 2007) is one of the most widely used phylogenetic software packages to infer molecular and epidemiological parameters in viral epidemics. Coapplicant Alexei Drummond is the main developer of BEAST. We extend BEAST such that we can accurately estimate both the within- and between-patient evolutionary rate on the same dataset, the Swiss Cohort. Specifically, we will modify our method such that we can estimate individual rates for the different transmission groups (MSMs, HETs, IDUs).
Based on these rate estimates, we will be able to investigate the plausibility of different models trying to explain the special structure of HIV phylogenies.
|Keywords / Suchbegriffe||HIV, evolution, viral sequences|
|Project leadership and contacts /
Projektleitung und Kontakte
|Funding source(s) /
|SNF (Personen- und Projektförderung), Others
Swiss HIV Cohort Study
|In collaboration with /
In Zusammenarbeit mit
|Duration of Project / Projektdauer||Jan 2010 to Jan 2012|