Asymptomatic HIV infection is characterized by rapid turnover of HIV RNA in plasma and lymph nodes but not of latently infected lymph-node CD4+ T cells

Stellbrink, H. J.; J, van Lunzen; Ft, Hufert; Fröschle, G.; Wolf-Vorbeck, G; Zöllner, Bernhard; Albrecht, Helmut; Greten, H.; Rácz, Paul; Tenner-Rácz, Klara

doi:10.1097/00002030-199709000-00004

Cited by 39 publications

(11 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The vast majority of HIV proviral DNA is detected in CD4 + T lymphocytesin lymphoid tissue 11, 12 . In blood, most HIV DNA can be found in central memory (TCM) and in transitional memory T cells (TTM); these cells maintain the reservoir because of their intrinsic capacity to persist through homeostatic proliferation and renewal 13 .…”

Section: Hiv Reservoirs: Obstacles To a Curementioning

confidence: 99%

Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs

et al. 2013

Self Cite

View full text Add to dashboard Cite

Antiretroviral therapy for HIV infection requires life-long access and strict adherence to regimens that are both expensive and associated with toxicities. There is growing recognition that a curative intervention will be needed to fully stop the epidemic. The failure to eradicate HIV infection during long-term antiretroviral therapy reflects the intrinsic stability of the viral genome in latently infected CD4+ T cells and other cells and perhaps ongoing low-level viral replication. Heterogeneity in latently infected cell populations and homeostatic proliferation of infected cells may influence the dynamics of virus production and persistence. Chronic immune activation, inflammation and immune dysfunction persist despite potent antiretroviral therapy and likely have important effects on the size and distribution of the viral reservoir. The inability of the immune system to recognize cells harboring latent virus and to eliminate cells actively producing virus represents the biggest challenge to finding a cure. In this perspective, we highlight new approaches toward unraveling the complex virus-host interactions that lead to persistent infection and latency and discuss the rationale for combining novel therapeutic strategies with current antiretroviral treatment options with the goal of curing HIV disease.

show abstract

Section: Hiv Reservoirs: Obstacles To a Curementioning

confidence: 99%

Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…A large pool of FDC-associated virus is present even early in infection before seroconversion (Schacker et al 2000). When one considers the amount of virus in the FDC network and the rapid loss of FDC-associated virus during treatment with HIV-1 reverse transcriptase (RT) and protease inhibitors (Cavert et al 1997;Wong et al 1997;Stellbrink et al 1997;Tenner-Racz et al 1998;Orenstein et al 1999), it is conceivable that FDCs have the potential to in£uence HIV-1 dynamics during antiretroviral therapy. Moreover, the FDC pool of virus may be able to perpetuate infection, as FDC-associated virus is highly infectious (Heath et al 1995) and may remain infectious for long periods (Burton et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Influence of follicular dendritic cells on HIV dynamics

Hlavacek

Stilianakis

Perelson

2000

Phil. Trans. R. Soc. Lond. B

View full text Add to dashboard Cite

In patients infected with human immunodeficiency virus type 1 (HIV-1), a large amount of virus is associated with follicular dendritic cells (FDCs) in lymphoid tissue. To assess the influence of FDCs on viral dynamics during antiretroviral therapy we have developed a mathematical model for treatment of HIV-1 infection that includes FDCs. Here, we use this model to analyse measurements of HIV-1 dynamics in the blood and lymphoid tissue of a representative patient, who was treated with a combination of HIV-1 reverse transcriptase and protease inhibitors. We show that loss of virus from FDCs during therapy can make a much larger contribution to plasma virus than production of virus by infected cells. This result challenges the notion that long-lived infected cells are a significant source of HIV-1 during drug therapy. Due to release of FDC-associated virus, we find that it is necessary to revise upward previous estimates of c, the rate at which free virus is cleared, and delta, the rate at which productively infected cells die. Furthermore, we find that potentially infectious virus, present before treatment, is released from FDCs during therapy and that the persistence of this virus can be affected by whether therapy includes reverse transcriptase inhibitors.

show abstract

“…Inhibitory KIRs play an important role in NK cell "education" and authorize the extent of their functional capacity during maturation (4,(13)(14); this occurs primarily in lymph nodes in the face of vigorous HIV-1 replication (10,32). Thus, by disrupting the HLA-B*5703-KIR3DL1 interaction, the G9E variant could modulate the education of maturing KIR3DL1 ϩ NK cells.…”

mentioning

confidence: 99%

An Early HIV Mutation within an HLA-B*57-Restricted T Cell Epitope Abrogates Binding to the Killer Inhibitory Receptor 3DL1

Brackenridge

Evans

Toebes

et al. 2011

J Virol

View full text Add to dashboard Cite

Mutations within MHC class I-restricted epitopes have been studied in relation to T cell-mediated immune escape, but their impact on NK cells via interaction with killer Ig-like receptors (KIRs) during early HIV infection is poorly understood. In two patients acutely infected with HIV-1, we observed the appearance of a mutation within the B*57-restricted TW10 epitope (G9E) that did not facilitate strong escape from T cell recognition. The NK cell receptor KIR3DL1, carried by these patients, is known to recognize HLA-B*5703 and is associated with good control of HIV-1. Therefore, we tested whether the G9E mutation influenced the binding of HLA-B*5703 to soluble KIR3DL1 protein by surface plasmon resonance, and while the wild-type sequence and a second (T3N) variant were recognized, the G9E variant abrogated KIR3DL1 binding. We extended the study to determine the peptide sensitivity of KIR3DL1 interaction with epitopes carrying mutations near the C termini of TW10 and a second HLA-B*57-restricted epitope, IW9. Several amino acid changes interfered with KIR3DL1 binding, the most extreme of which included the G9E mutation commonly selected by HLA-B*57. Our results imply that during HIV-1 infection, some early-emerging variants could affect KIR-HLA interaction, with possible implications for immune recognition.

show abstract

Asymptomatic HIV infection is characterized by rapid turnover of HIV RNA in plasma and lymph nodes but not of latently infected lymph-node CD4+ T cells

Cited by 39 publications

References 16 publications

Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs

Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs

Influence of follicular dendritic cells on HIV dynamics

An Early HIV Mutation within an HLA-B*57-Restricted T Cell Epitope Abrogates Binding to the Killer Inhibitory Receptor 3DL1

Contact Info

Product

Resources

About