Population genetic modeling of viruses

Population genetic models provide a powerful approach to the study of the evolutionary dynamics of viruses. The application of population genetic approaches to viruses has grown in recent years and has been facilitated by advances in sequencing technologies that make it feasible to obtain multiple 'genetic' snapshots of evolving viral populations through time. Populations of viruses are often shaped by a combination of high mutation rates, strong selection, large population sizes, and recurrent bottlenecks, and thus inhabit a different region of population genetic "parameter space" to cellular organisms. In this chapter, we discuss how traditional and novel population genetic models have provided insights into virus evolutionary processes and the means by which pathogenic viruses may be combatted. In particular, we illustrate how population genetics can be used to understand adaptive evolution in viruses and review recent work on whether viral evolution can be predicted

Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape

Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in “shock-and-kill” cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to “corner” the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection