The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo
Open accessAbstract
HIV-1 persists in a latent reservoir despite antiretroviral therapy (ART). This reservoir is the major barrier to HIV-1 eradication. Current approaches to purging the latent reservoir involve pharmacologic induction of HIV-1 transcription and subsequent killing of infected cells by cytolytic T lymphocytes (CTLs) or viral cytopathic effects. Agents that reverse latency without activating T cells have been identified using in vitro models of latency. However, their effects on latently infected cells from infected individuals remain largely unknown. Using a new ex vivo assay, we demonstrate that none of the latency-reversing agents (LRAs) tested induced outgrowth of HIV-1 from the latent reservoir of patients on ART. Using a quantitative reverse transcription PCR assay specific for all HIV-1 mRNAs, we demonstrate that LRAs that do not cause T cell activation do not induce substantial increases in intracellular HIV-1 mRNA in patient cells; only the protein kinase C agonist bryostatin-1 caused significant increases. These findings demonstrate that current in vitro models do not fully recapitulate mechanisms governing HIV-1 latency in vivo. Further, our data indicate that non-activating LRAs are unlikely to drive the elimination of the latent reservoir in vivo when administered individually.
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Imamichi, H., Smith, M., Adelsberger, J. W., Izumi, T., Scrimieri, F., Sherman, B. T., Rehm, C. A., Imamichi, T., Pau, A., Catalfamo, M., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1917876117 · Cited by 251
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Metadata
- Authors
- Bullen, C. K., Laird, G. M., Durand, C. M., Siliciano, J. D., & Siliciano, R. F.
- Venue
- Nature Medicine
- Published
- 2014-03-23
- Volume
- 20
- Issue
- 4
- Pages
- 425-429
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2038598840
- Cited by
- 488
- References
- 5
- FWCI
- 29.01
- Type
- journal article
- Language
- en
- Open access
- green
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- Bullen, C. K., Laird, G. M., Durand, C. M., Siliciano, J. D., & Siliciano, R. F. (2014). New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo. Nature Medicine. https://doi.org/10.1038/nm.3489
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