Evolution of information in HIV-1 protease

EVENT : C3BI Seminars

Main speaker : Chris Adami, from Michigan State University Date : 06-06-2019 at 02:00 pm Location : Auditorium Francois Jacob – BIME (26) ,Institut Pasteur, Paris

Highly-active anti-retroviral therapy has been extremely effective at maintaining low levels of viral load in HIV-infected individuals, but emerging drug resistance is threatening those gains. When therapy is interrupted even briefly, HIV can evolve resistance to one or multiple drugs. Understanding how to stop viral evolution is an important goal of current research. I use HIV-1 protease sequences from public databases to study the dynamics of evolution over a span of nearly ten years, to compare patterns of adaptation in populations that are drug-naive to those that have taken one or multiple protease inhibitors. Using information theory, I show that the amount of information stored in protease sequences of patients that are on drug therapy has been increasing over time, suggesting that they are adapting to the drugs. In comparison, there is no increase in information in the sequences of patients that are drug naive. However, for the virus the increase in information comes at a price: because most of the information is stored in correlations between residues, the sequences are evolving into a more rugged area of the fitness landscape, which could make further evolution more difficult. While the data up to 2006 do not suggest a slowing down of evolution, such a trend may exist in data from later years not analyzed here.

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