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Rapid evolution of HIV-1 to functional CD8⁺ T cell responses in humanized BLT mice.

Dudek, Timothy E and No, Daniel C and Seung, Edward and Vrbanac, Vladimir D and Fadda, Lena and Bhoumik, Priyasma and Boutwell, Christian L and Power, Karen A and Gladden, Adrianne D and Battis, Laura and Mellors, Elizabeth F and Tivey, Trevor R and Gao, Xiaojiang and Altfeld, Marcus and Luster, Andrew D and Tager, Andrew M and Allen, Todd M (2012) Rapid evolution of HIV-1 to functional CD8⁺ T cell responses in humanized BLT mice. Science translational medicine, 4 (143). 143ra98. ISSN 1946-6242

Abstract

The development of mouse/human chimeras through the engraftment of human immune cells and tissues into immunodeficient mice, including the recently described humanized BLT (bone marrow, liver, thymus) mouse model, holds great promise to facilitate the in vivo study of human immune responses. However, little data exist regarding the extent to which cellular immune responses in humanized mice accurately reflect those seen in humans. We infected humanized BLT mice with HIV-1 as a model pathogen and characterized HIV-1-specific immune responses and viral evolution during the acute phase of infection. HIV-1-specific CD8(+) T cell responses in these mice were found to closely resemble those in humans in terms of their specificity, kinetics, and immunodominance. Viral sequence evolution also revealed rapid and highly reproducible escape from these responses, mirroring the adaptations to host immune pressures observed during natural HIV-1 infection. Moreover, mice expressing the protective HLA-B*57 allele exhibited enhanced control of viral replication and restricted the same CD8(+) T cell responses to conserved regions of HIV-1 Gag that are critical to its control of HIV-1 in humans. These data reveal that the humanized BLT mouse model appears to accurately recapitulate human pathogen-specific cellular immunity and the fundamental immunological mechanisms required to control a model human pathogen, aspects critical to the use of a small-animal model for human pathogens.

Item Type: Article
Date Deposited: 15 Jul 2016 00:45
Last Modified: 15 Jul 2016 00:45
URI: https://oak.novartis.com/id/eprint/30289

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