Research ArticleHIV

Rapid Evolution of HIV-1 to Functional CD8+ T Cell Responses in Humanized BLT Mice

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Science Translational Medicine  18 Jul 2012:
Vol. 4, Issue 143, pp. 143ra98
DOI: 10.1126/scitranslmed.3003984

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Mirror, Mirror

One limitation of using animal models of disease is that there’s no magic mirror to tell you which one best reflects human disease. Instead, most animal disease models mimic some aspects of the human condition, but may not recapitulate the disease in its entirety. This limitation is especially true for HIV infection because the virus does not naturally infect mice—the model of choice for biomedical research. Attempts to “humanize” immunodeficient mice through grafting of human immune cells may reconfigure the mouse from a distorting funhouse mirror into a well-lit vanity one. Now, Dudek et al. use humanized BLT (brain, liver, thymus) mice to study human immune responses to HIV.

The authors found that HIV-1–specific immune responses in BLT mice mimicked those in humans in terms of specificity, kinetics, and dominant target. Importantly, HIV adapted to the immune responses in these mice just as it does in humans, evolving rapidly to escape from the selective pressure. Indeed, an HLA allele that is protective in humans induced similar protective immune responses in these mice. Although no animal model may perfectly reflect human disease, for HIV infection, humanized BLT mice may be one of the fairest of them all.