Establishing the HIV reservoir: HIV-susceptible cells and the signals that recruit them
| Autor: | Thomas Alexander Packard, Eytan Herzig, Nadia R Roan, Warner C Greene |
|---|---|
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 198:125.1-125.1 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.198.supp.125.1 |
| Popis: | HIV-1 infected individuals require lifelong antiretroviral therapy (ART). If ART is discontinued, HIV rebounds from a reservoir of cells containing latent provirus—persistence of this reservoir is the most significant roadblock to curing people infected with HIV. The HIV reservoir is formed rapidly following infection and remains relatively stable throughout the lifetime of an infected individual on ART: this reservoir persistence likely stems from a central memory phenotype of host T cells. Transmitted HIV binds and enters cellular targets via the co-receptor, CCR5, which is primarily expressed on effector memory CD4 T cells. How does HIV rapidly establish a central memory reservoir? Abortive HIV infection of lymphoid CD4 T cells activates IFI16, which can form inflammasomes, triggering pyroptosis. IFI16 also can activate STING to produce type 1 interferon and the CCL2 chemokine. Thus, an early innate immune response to HIV sets up a zone of inflammation. CCL2 attracts cells expressing the receptor CCR2. Strikingly, CCR2 delineates a population of lymphoid CD4 T which co-express CCR5 and markers of central memory (CCR7 & CD62L)—precisely the same type of cells that make up the viral reservoir. We found that these lymphoid CCR2+ T cells migrate in response to CCL2 and are susceptible to infection with R5- or X4-tropic strains of HIV. We propose that CCL2 produced early in HIV infection lures CCR2+ central memory T cells to the site of inflammation. Here these cells can become productively infected and produce virus, or become latently infected and contribute to the stable reservoir. These findings raise the possibility that inflammation contributes to seeding of the latent reservoir, and might be reduced by antagonists of CCL2/CCR2. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|