Establishing the HIV reservoir: HIV-susceptible cells and the signals that recruit them
| Autor: | Thomas Alexander Packard, Xiaoyu Luo, Zachary W. Grimmett, Eytan Herzig, Nadia R. Roan, Warner C. Greene |
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| Rok vydání: | 2018 |
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| Zdroj: | The Journal of Immunology. 200:182.4-182.4 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.200.supp.182.4 |
| Popis: | HIV infection rapidly causes localized inflammation, which contributes to viral pathogenesis by recruiting cells to become infected. At the same time, the stable HIV reservoir forms swiftly and persists over the life of the individual, likely due to infection of long-lived central memory CD4 T cells. The elimination/control of the reservoir is critical to an HIV cure. We sought to understand how host inflammatory responses to HIV drive the formation of the viral reservoir. Our early studies found that CD4 T cells rapidly produce the chemoattractant CCL2 following HIV infection, and this host response is dependent on HIV reverse transcription but not integration of viral DNA. We proposed that CCL2 produced early in response to HIV lures cells bearing the receptor—CCR2—to the zone of infection. Using mass cytometry, we identified a novel population of human lymphoid CCR2+ CD4 T cells that co-express CCR5 and have a central memory phenotype, along with markers associated with the HIV reservoir. We found that CCR2/5+ cells migrate in response to CCL2, fuse to R5 and X4-tropic HIV and support productive and latent infection. To measure the HIV reservoir in vivo, we sorted CCR2/5+ cells from PBMCs of HIV-infected ART-suppressed individuals and measured integrated HIV proviral DNA. Our preliminary findings show that CCR2/5+ cells have significantly higher levels of integrated HIV than CCR-negative memory (12-fold, p = 0.046) or naïve cells (28-fold, p = 0.012). We propose that HIV hijacks the host response to the virus to recruit CCR2+ cells, which may become latently infected to form the long-lived reservoir, providing a link between inflammation and reservoir seeding. We are now testing if blockade of CCL2 disrupts formation of the HIV reservoir. |
| Databáze: | OpenAIRE |
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