|Title / Titel||Measuring the heritability of set-point viral load in HIV-1 infections|
|Abstract (PDF, 14 KB)|
|Summary / Zusammenfassung||2.1 Background
HIV evolves rapidly and many studies have focused on the evolution of HIV virulence, i.e. the host mortality rate due to the infection (Müller et al. 2006, Ariën et al. 2007, Fraser et al. 2007). Surprisingly, studies tend to show that the level of virulence (estimated through the set-point viral load) is stable over the last two decades (Müller et al. 2006, Herbeck et al. 2008). This could mean that HIV virulence does not evolve or that it has reached an evolutionary equilibrium early in the pandemic.
Generally speaking, natural selection can act on a trait if it is variable among organisms, if it is heritable and if its value affects the fitness of the organism (Lewontin 1970). In the case of HIV, there currently is no satisfying estimate of virulence heritability, because any such estimate requires information on the transmission chain (i.e. who infected whom), which is difficult to obtain.
2.2 Study Aims
We want to estimate the heritability of HIV-1 virulence from a donor to a recipient infection. Our idea is to use phylogenetic methods to utilise the large amount of genetic information that is available and thereby to overcome the lack of data on the donor-recipient pairs.
This study has implications for the understanding of HIV virulence. 15% of the variance observed in set-point viral load can be explained by host alleles (Fellay et al. 2007). Estimating virulence heritability would allow us to obtain a similar estimate for the virus genotype. More generally, this study is one of the first to combine phylogenetic methods and clinical data to study heritability of viral traits on a larger scale.
2.3 Study Design
We will first build a phylogeny of HIV-1 infected patients based on nucleotide sequences obtained from genotypic drug resistance tests performed while still drug naive and for whom at least three HIV RNA measurements are available before any treatment was started to calculate the set-point viral load. This will allow us to reconstruct an approximate transmission chain.
We will then measure the heritability of the trait (i.e. set-point viral load) in this phylogeny using classical phylogenetic methods (Blomberg et al. 2003).
|Publications / Publikationen||Alizon S, von Wyl V, Stadler T, Kouyos RD, Yerly S, et al. 2010 Phylogenetic Approach Reveals That Virus Genotype Largely Determines HIV Set-Point Viral Load. PLoS Pathog 6(9): e1001123. doi:10.1371/journal.ppat.1001123Weitere Informationen|
|Keywords / Suchbegriffe||HIV, trait heritability, virulence, evolution, transmission, viral setpoint, resistance database, hiv pol gene, nucleotide sequences, swiss hiv cohort study, phylogeny|
|Project leadership and contacts /
Projektleitung und Kontakte
|Funding source(s) /
|SNF (Personen- und Projektförderung)
Swiss HIV Cohort Study
|Duration of Project / Projektdauer||Apr 2009 to Apr 2011|