Sometimes it pays to be recognized

Model HIV may not always want to go unnoticed. It is known that HIV replicates more efficiently in TH cells that have been activated, and this presents the virus with a bit of a dilemma – it certainly doesn’t pay to be recognized by CTLs, the hired assassins of the immune system. But there’s also a possible benefit in triggering the activation of the TH cells that they’ve infected. Where does the balance lie? Is it conceivable that there are some conditions where it is better for HIV epitopes to be recognized than to be ignored?

To answer this question, scientists have built a complex mathematical model of interactions between TH cells, CTLs, antigen-presenting cells and viruses. They set up two different versions of the model – one with a virus that infects non-immune cells (like HCV infecting hepatocytes), and one with a virus that infects T cells (like HIV). The results are quite striking – in the case of HCV, evasion always pays off. But in the case of HIV, the dependence on TH activation seems to sometimes favor virus epitopes that are strongly recognized by cellular immune system. The authors propose that recognition of HIV epitopes by TH cells can be beneficial for the long-term survival of the virus within the body. Another key variable is how many TH cells are activated in the body by pathogens other than HIV. If this “background activation” is strong, HIV obtains no payoffs from being recognized. Studying the sequence data confirms that in the capsid genes (Gag) it is TH epitopes, rather than CTL epitopes, that are constrained and that epitopes stay the same within patient viral populations rather than between patients, again implicating chronic internal transmission between cells.

There is an important practical implication of these findings. If this model is correct, then HIV vaccines based on TH epitopes might prove counterproductive, playing into the hands of the virus. Instead, vaccines should target only CTL-specific viral epitopes.

 

HIV Plays (and Wins) a Game of T Cell Brinkmanship. (2013) PLoS Biol 11(4): e1001521. doi:10.1371/journal.pbio.1001521

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