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ECOLOGY SEMINAR: Dissecting host and viral contributions to set point viral load in HIV

Sebastian Bonhoeffer, Professor of Environmental System Science, Institute of Integrative Biology, ETH Zürich
Oct
31
Fall 2017
Oct. 31, 3:30 pm - 4:30 pm
Ecology Auditorium

Reception follows seminar in lobby at 4:30 p.m. Host: John Drake. Co-sponsored by the UGA Center for the Ecology of Infectious Diseases.

Abstract:
Set point viral load (spVL) is a key determinant of disease progression in HIV infection.  In this talk I will discuss to what extent spVL is under the genetic control of the virus or the host. I will give a personal view on the applicability and limitations of the various methods that have been employed to dissect the host versus viral contributions. Genome wide association studies (GWAS) are typically used to estimate the host genetic contribution. Due to their multiple testing burden they are limited to common genetic polymorphisms with strong effect, and thus tend to underestimate the host genetic contribution. Donor-recipient regression (DR) and phylogenetic methods (PMs) are used to quantify the viral genetic contribution. DR is often limited by the availability of donor-recipient pairs, but is robust to effects of selection. PMs can be used on large patient populations for which viral sequence data is available. PMs typically assume that genetic variance accumulates by neutral drift. However, in the presence of selection their accuracy can be severely compromised. I will conclude by discussing possible options to improve both PM and DR based methods and summarise our current knowledge of the respective contributions of host and virus to spVL.