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closePredicting limited evolution of "drug resistance" against activation inhibitors
Posted by ViktorMüller on 28 Jul 2012 at 04:18 GMT
reduce the activation status/potential
http://plosone.org/article/info:doi/10.1371/journal.pone.0041832#article1.body1.sec4.p4
A further advantage of drugs that, like SIL, act by downregulating the activation (and thereby the susceptibility) of target cells, might be that the selection pressure on the virus to evolve compensatory changes against these drugs is likely to be much lower than the pressure towards drug resistance exerted by classic antiretrovirals. A potential compensatory change would involve mutations that increase the ability of the virus to induce immune activation: however, unlike restoring enzyme function and replication capacity in the face of enzyme inhibitors, this is an indirect effect, the benefits of which are shared by the wt viruses in the same individual -- which weakens selection and slows down adaptive evolution. These arguments have emerged from a mathematical/simulation model presented here:
Bartha, I., Simon, P. & V. Müller (2008) Has HIV evolved to induce immune pathogenesis? Trends Immunol 29, 322-328.
http://www.sciencedirect.com/science/article/pii/S1471490608001269