Reactivation of latent HIV-1 in central memory CD4+T cells through TLR-1/2 stimulation
Public Deposited- Creator
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Novis, Camille L
- Other Affiliation: Division of Microbiology and Immunology, Department of Pathology, University Of Utah School of Medicine, Salt Lake City, USA
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Archin, Nancie M
- Affiliation: School of Medicine, Division of Infectious Diseases
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Buzon, Maria J
- Other Affiliation: Infectious Disease Division, Massachusetts General Hospital, Boston, USA; Ragon Institute of MGH, MIT and Harvard, Boston, USA
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Verdin, Eric
- Other Affiliation: Gladstone Institute of Virology and Immunology, San Francisco, USA
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Round, June L
- Other Affiliation: Division of Microbiology and Immunology, Department of Pathology, University Of Utah School of Medicine, Salt Lake City, USA
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Lichterfeld, Mathias
- Other Affiliation: Infectious Disease Division, Massachusetts General Hospital, Boston, USA
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Margolis, David
- Affiliation: School of Medicine, Division of Infectious Diseases
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Planelles, Vicente
- Other Affiliation: Division of Microbiology and Immunology, Department of Pathology, University Of Utah School of Medicine, Salt Lake City, USA
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Bosque, Alberto
- Other Affiliation: Division of Microbiology and Immunology, Department of Pathology, University Of Utah School of Medicine, Salt Lake City, USA
- Abstract
- Background Toll-like receptors (TLRs) are crucial for recognition of pathogen-associated molecular patterns by cells of the innate immune system. TLRs are present and functional in CD4+ T cells. Memory CD4+ T cells, predominantly central memory cells (TCM), constitute the main reservoir of latent HIV-1. However, how TLR ligands affect the quiescence of latent HIV within central memory CD4+ T cells has not been studied. Results We evaluated the ability of a broad panel of TLR agonists to reactivate latent HIV-1. The TLR-1/2 agonist Pam3CSK4 leads to viral reactivation of quiescent HIV in a model of latency based on cultured TCM and in resting CD4+ T cells isolated from aviremic patients. In addition, we investigated the signaling pathway associated with Pam3CSK4 involved in HIV-1 reactivation. We show that the transcription factors NFκB, NFAT and AP-1 cooperate to induce viral reactivation downstream of TLR-1/2 stimulation. Furthermore, increasing levels of cyclin T1 is not required for TLR-mediated viral reactivation, but induction of viral expression requires activated pTEFb. Finally, Pam3CSK4 reactivates latent HIV-1 in the absence of T cell activation or proliferation, in contrast to antigen stimulation. Conclusions Our findings suggest that the signaling through TLR-1/2 pathway via Pam3CSK4 or other reagents should be explored as an anti-latency strategy either alone or in combination with other anti-latency drugs.
- Date of publication
- October 24, 2013
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Novis et al.; licensee BioMed Central Ltd.
- Journal title
- Retrovirology
- Journal volume
- 10
- Journal issue
- 1
- Page start
- 119
- Language
- English
- Bibliographic citation
- Retrovirology. 2013 Oct 24;10(1):119
- Publisher
- BioMed Central
Relations
- Parents:
This work has no parents.
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