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Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection
Abstract
The capacity of HIV-1 to establish latent infection of CD4+ T cells may allow viral persistence despite immune responses and antiretroviral therapy. Measurements of infectious virus and viral RNA in plasma and of infectious virus, viral DNA and viral messenger RNA species in infected cells all suggest that HIV-1 replication continues throughout the course of infection. Uncertainty remains over what fraction of CD4+ T cells are infected and whether there are latent reservoirs for the virus. We show here that during the asymptomatic phase of infection there is an extremely low total body load of latently infected resting CD4+ T cells with replication-competent integrated provirus (<10(7) cells). The most prevalent form of HIV-1 DNA in resting and activated CD4+ T cells is a full-length, linear, unintegrated form that is not replication competent. The infection progresses even though at any given time in the lymphoid tissues integrated HIV-1 DNA is present in only a minute fraction of the susceptible populations, including resting and activated CD4+ T cells and macrophages.
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“HAART profoundly reduces viral replication in cells that support HIV-1 infection and reduces plasma viremia to a minimal level but neither suppresses low-level viral genome expression and replication in tissues nor targets the latently infected cells that serve as a reservoir for HIV-1”
From RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection (2014) · cites this paper as [4]
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Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy
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Self-citationRecovery of replication-competent HIV despite prolonged suppression of plasma viremia
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Self-citationPresence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy
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Metadata
- Authors
- Chun, T.-W., Carruth, L., Finzi, D., Shen, X., DiGiuseppe, J. A., Taylor, H., Hermankova, M., Chadwick, K., Margolick, J., Quinn, T. C., Kuo, Y.-H., Brookmeyer, R., Zeiger, M. A., Barditch-Crovo, P., & Siliciano, R. F.
- Affiliations
- Johns Hopkins University (US)
- National Institutes of Health (US)
- ORCID
- Venue
- Nature
- Published
- 1997-05
- Volume
- 387
- Issue
- 6629
- Pages
- 183-188
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2030844138
- Cited by
- 2,050
- References
- 29
- Citations by year
- 2026: 29 · 2025: 47 · 2024: 48 · 2023: 59 · 2022: 54 · 2021: 56 · 2020: 80 · 2019: 79 · 2018: 102 · 2017: 81 · 2016: 98 · 2015: 79 · 2014: 86 · 2013: 87 · 2012: 74
- FWCI
- 25.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Keywords
- HIV-1, latent viral reservoir, CD4+ T cells, integrated provirus, viral persistence, asymptomatic HIV infection, activated T cells, macrophages, viral DNA, viral RNA, antiretroviral therapy
- MeSH terms
- Cells, Cultured, DNA, Viral, Humans, Immunologic Memory, Lymph Nodes, Lymphocyte Activation, Macrophages, Proviruses, Virus Replication, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Polymerase Chain Reaction, Virus Integration, Leukocyte Common Antigens, Virus Latency, Coculture Techniques, Anti-HIV Agents, Viral Load
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