Cellular HIV Reservoirs and Viral Rebound from the Lymphoid Compartments of 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine (EFdA)-Suppressed Humanized Mice
| Autor: | Mary E. Moreno, Pheroze Joshi, Sofiya A. Galkina, Ma Somsouk, Ekaterina Maidji, Jose M. Rivera, Cheryl A. Stoddart, Galina Kosikova |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lymphoid Tissue 030106 microbiology antiretroviral therapy lcsh:QR1-502 Mice Transgenic HIV Infections In situ hybridization macrophage Virus Replication DC-SIGN Microbiology Article lcsh:Microbiology Virus Transgenic 03 medical and health sciences chemistry.chemical_compound Mice Deoxyadenosine cellular reservoir In vivo Virology Animals Humans RNAscope Disease Reservoirs biology Deoxyadenosines Animal virus diseases HIV Reverse transcriptase infection Disease Models Animal 030104 developmental biology Infectious Diseases Viral replication chemistry Disease Models biology.protein HIV-1 HIV/AIDS Immunohistochemistry Reverse Transcriptase Inhibitors Female |
| Zdroj: | Viruses, vol 11, iss 3 Viruses Volume 11 Issue 3 Viruses, Vol 11, Iss 3, p 256 (2019) |
| Popis: | Although antiretroviral therapy (ART) greatly suppresses HIV replication, lymphoid tissues remain a sanctuary site where the virus may replicate. Tracking the earliest steps of HIV spread from these cellular reservoirs after drug cessation is pivotal for elucidating how infection can be prevented. In this study, we developed an in vivo model of HIV persistence in which viral replication in the lymphoid compartments of humanized mice was inhibited by the HIV reverse transcriptase inhibitor 4&prime ethynyl-2-fluoro-2&prime deoxyadenosine (EFdA) to very low levels, which recapitulated ART-suppression in HIV-infected individuals. Using a combination of RNAscope in situ hybridization (ISH) and immunohistochemistry (IHC), we quantitatively investigated the distribution of HIV in the lymphoid tissues of humanized mice during active infection, EFdA suppression, and after drug cessation. The lymphoid compartments of EFdA-suppressed humanized mice harbored very rare transcription/translation-competent HIV reservoirs that enable viral rebound. Our data provided the visualization and direct measurement of the early steps of HIV reservoir expansion within anatomically intact lymphoid tissues soon after EFdA cessation and suggest a strategy to enhance therapeutic approaches aimed at eliminating the HIV reservoir. |
| Databáze: | OpenAIRE |
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