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New Simulation Method Sheds Light on the Evolution of HIV

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Until recently, it was a commonly held belief among HIV-1 researchers that the virus evolves at a relatively slow pace during early infection. But a new computer simulation that reconstructs the speed of HIV-1 protein region evolution from a single virus has challenged that notion. The University of Adelaide's Jack Da Silva published a paper in the March issue of Genetics that described this new computational method. It simulates population changes due to the killing of infected cells by the immune system, together with recombination and random genetic changes. Da Silva's simulation demonstrated that even with low population levels, HIV evolves rapidly.

"This work shows that the previously reported extremely rapid evolution of the virus in early infection is consistent with reports of the virus undergoing a drastic population bottleneck of a single genome during sexual transmission between hosts," Da Silva says. "It also shows that this requires that a strong immune response from HIV-1-specific CD8+ T-cells weakens over the duration of early infection, roughly 200 days."

To mitigate errors due to stochastic factors, Da Silva's technique replicates the evolution 1,000 times to calculate average outcomes. The simulation is implemented by tracking the frequencies of viral haplotypes across viral generations within the host. Further, the most challenging aspect of developing this method was simulating recombination among several loci or protein-coding regions.

While he is still refining the technique, Da Silva says given these early results, he is hopeful that the data on the dynamics of adaptation of HIV-1 generated by this new simulation method will be applied to drug development.

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