the role of recombination for the coevolutionary dynamics of hiv and the immune response重组的作用共同进化动力学的艾滋病毒和免疫应答.pdfVIP

The Role of Recombination for the Coevolutionary Dynamics of HIV and the Immune Response 1 1 2 1 Rafal Mostowy *, Roger D. Kouyos , David Fouchet , Sebastian Bonhoeffer ´ ´ ´ 1 Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland, 2 Biometrie et Biologie Evolutive, Universite de Lyon, Villeurbanne, France Abstract The evolutionary implications of recombination in HIV remain not fully understood. A plausible effect could be an enhancement of immune escape from cytotoxic T lymphocytes (CTLs). In order to test this hypothesis, we constructed a population dynamic model of immune escape in HIV and examined the viral-immune dynamics with and without recombination. Our model shows that recombination (i) increases the genetic diversity of the viral population, (ii) accelerates the emergence of escape mutations with and without compensatory mutations, and (iii) accelerates the acquisition of immune escape mutations in the early stage of viral infection. We see a particularly strong impact of recombination in systems with broad, non-immunodominant CTL responses. Overall, our study argues for the importance of recombination in HIV in allowing the virus to adapt to changing selective pressures as imposed by the immune system and shows that the effect of recombination depends on the immunodominance pattern of effector T cell responses. Citation: Mostowy R, Kouyos RD, Fouchet D, Bonhoeffer S (201