The Cost of Escape

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Science  19 Nov 2004:
Vol. 306, Issue 5700, pp. 1261
DOI: 10.1126/science.306.5700.1261c

Cytotoxic CD8 T cells (CTLs) begin their assault on the HIV pathogen soon after infection occurs, and the efficiency with which they achieve early control is a deciding factor in the course infection takes. Conversely, the virus defends itself by mutating the epitopes targeted by the CTLs in an attempt to escape recognition. Jones et al. explored which characteristics of early CTL responses to HIV corresponded with the subsequent ability to control the viral load.

In an individual showing good viral control, the number and breadth of epitopes recognized by CTLs were relatively large, in contrast to the strong focus of CTLs on a handful of immuno-dominant epitopes in two individuals exhibiting poor viral control. In these two people, new viruses with numerous CTL epitope mutations appeared soon after infection, suggesting that early selective pressure from CTLs had been countered successfully by the virus. On the other hand, the individual with good viral control carried viruses with far fewer mutations, consistent with the relatively slow emergence of new escape mutants in the months after the acute phase of infection. Early control thus appears to be determined by broad recognition of multiple viral epitopes, increasing both the opportunity for viral detection by CTLs and the potential cost of escape mutations to intrinsic viral fitness. — SJS

J. Exp. Med., 200, 1243 (2004).

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