Intra-patient evolution of HIV

HIV is often called the ultimate evolver, since it has an extraordinarily high mutation rate and different virus genomes within a patient recombine their genetic material frequently. As a result, the diversity of the viral population within a patient can reach a few percent in certain parts of the HIV genome, which exceeds the divergence between human and chimp. Since time series data on HIV evolution is available and its biology is exceptionally well understood, HIV provides an ideal model system in which fundamental questions of evolution can be addressed.


Observing evolution in action: the continual adaptation of HIV during chronic infection

In collaboration with the group of Prof. Jan Albert at the Karolinska Institute in Stockholm, we sequence HIV populations from frozen blood samples taken from individual patients every couple of months. Using this data, we can follow the evolution of viral proteins through time and study how the viral population responds to drug treatment. This data gives us the unique opportunity to observe evolution while it is happening, rather than having to infer the dynamics from a static snapshot.

Opens external link in new windowRecombination Rate and Selection Strength in HIV Intra-patient Evolution. Neher and Leitner, PLoS Comput Biol (2010) vol. 6 (1) pp. e1000660


Modeling CTL escape and evolution during acute infection

During the months following infection, the HIV population undergoes a few (~8) rapid selective sweeps, i.e., substitutions of amino-acids. These substitutions confer an advantage somewhere from a few percent to 50 percent or more to the mutant virus and rapidly replace the founding virus. These rapid escapes inform us about how strongly the immune system targets specific epitopes in the viral proteome.

Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses.  V.V. Ganusov*, R.A. Neher* and Alan S.  Perelson.