Varied sensitivity to therapy of HIV-1 strains in CD4+ lymphocyte sub-populations upon ART initiation

Heeregrave, Edwin J.; Geels, Mark J.; Baan, Elly; Sluis, Renée M. van der; Paxton, William A.; Pollakis, Georgios

doi:10.1186/1742-6405-7-42

Cited by 3 publications

(2 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Naïve and memory lymphocyte subsets differ in body distribution, proliferative capacity and expression levels of CCR5 and CXCR4, the main co-receptors for HIV-1 [12]–[17]. CD4 + memory T cells can be subdivided into phenotypically distinct subsets with different functions.…”

Section: Introductionmentioning

confidence: 99%

“…CD4 + lymphocytes are the main targets for HIV-1 infection with various sub-populations infected to a different extent [10] , [11] . Naïve and memory lymphocyte subsets differ in body distribution, proliferative capacity and expression levels of CCR5 and CXCR4, the main co-receptors for HIV-1 [12] – [17] . CD4 + memory T cells can be subdivided into phenotypically distinct subsets with different functions.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High CCR5 Density on Central Memory CD4+ T Cells in Acute HIV-1 Infection Is Mostly Associated with Rapid Disease Progression

et al. 2012

View full text Add to dashboard Cite

CD4+ central memory T cells play a critical role in the pathogenesis of simian immunodeficiency virus disease, and the CCR5 density on the surface of CD4 T cells is an important factor in human immunodeficiency virus (HIV)-1 disease progression. We hypothesized that quantifying central memory cells and CCR5 expression in the early stages of HIV-infection could provide useful prognostic information. We enrolled two different groups of acute HIV-infected subjects. One group progressed to CD4 T cell numbers below 250 cells/µl within 2 years (CD4 Low group), while the other group maintained CD4 cell counts above 450 cells/µl over 2 years (CD4 High group). We compared the CCR5 levels and percentage of CD4 subsets between the two groups during the 1st year of HIV infection. We found no differences between the two groups regarding the percentage of naïve, central memory and effector memory subsets of CD4 cells during the 1st year of HIV-1 infection. CCR5 levels on CD4+ CM subset was higher in the CD4 Low group compared with the CD4 High group during the 1st year of HIV-1 infection. High CCR5 levels on CD4 central memory cells in acute HIV infection are mostly associated with rapid disease progression. Our data suggest that low CCR5 expression on CD4 central memory cells protects CD4 cells from direct virus infection and favors the preservation of CD4+ T cell homeostasis.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High CCR5 Density on Central Memory CD4+ T Cells in Acute HIV-1 Infection Is Mostly Associated with Rapid Disease Progression

et al. 2012

View full text Add to dashboard Cite

show abstract

Lack of concordance between residual viremia and viral variants driving de novo infection of CD4+ T cells on ART

et al. 2016

View full text Add to dashboard Cite

BackgroundIn most patients, current antiretroviral therapy (ART) regimens can rapidly reduce plasma viral load. However, even after years of effective treatment, a significant proportion of patients show residual plasma viremia below the clinical detection limit. Although residual viremia might be associated with increased chronic immune activation and morbidity, its origin and its potential role in the replenishment of the viral reservoir during suppressive ART is not completely understood. We performed an in-depth genetic analysis of the total and episomal cell-associated viral DNA (vDNA) repertoire in purified CD4+ T cell subsets of three HIV-infected individuals, and used phylogenetic analysis to explore its relationship with plasma viruses.ResultsThe predominant proviral reservoir was established in naïve or memory (central and transitional) CD4+ T cell subsets in patients harboring X4- or R5-tropic viruses, respectively. Regardless of the viral tropism, most plasma viruses detected under suppressive ART resembled the proviral reservoir identified in effector and transitional memory CD4+ T-cell subsets in blood, suggesting that residual viremia originates from these cells in either blood or lymphoid tissue. Most importantly, sequences in episomal vDNA in CD4+ T-cells were not well represented in residual viremia.ConclusionsViral tropism determines the differential distribution of viral reservoir among CD4+ T-cell subsets. In spite of viral tropism, the effector and transitional memory CD4+ T-cells subsets are the main source of residual viremia during suppressive ART, even though their contribution to the total proviral pool is small. However, the lack of concordance between residual viremia and viral variants driving de novo infection of CD4+ T cells on ART may reflect the predominance of defective plasma HIV RNA genomes. These findings highlight the need for monitoring the multiple viral RNA/DNA persistence markers, based on their differential contribution to viral persistence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0282-9) contains supplementary material, which is available to authorized users.

show abstract

Analysis of Multiple Cell Reservoirs Expressing Unspliced HIV-1 gag-pol mRNA in Patients on Antiretroviral Therapy

et al. 2012

View full text Add to dashboard Cite

Aims Longitudinal percentage change of eight HIV-1 gag-pol mRNA cellular reservoirs from HIV-infected subjects on antiretroviral therapy was ascertained by simultaneous ultrasensitive subpopulation staining/hybridization in situ (SUSHI). Materials & methods Serial peripheral blood mononuclear cells were taken from three subjects with treatment success, limited response and viral breakthrough plasma viral load (PVL) profiles. SUSHI was carried out on monocytes, macrophages, CD4+ cells and naive, memory and activated T-cell reservoirs followed with broad light scatter flow cytometry. Results All gag-pol+ reservoirs declined in the treatment success patient and similar to PVL. Only some gag-pol+ reservoirs responded similarly to PVL for the limited treatment patient, and most gag-pol+ reservoirs increased 16 weeks prior to PVL breakthrough in the viral breakthrough patient. Conclusion SUSHI measures changes in a wide range of gag-pol+ reservoirs in response to antiretroviral therapy.

show abstract

Varied sensitivity to therapy of HIV-1 strains in CD4+ lymphocyte sub-populations upon ART initiation

Cited by 3 publications

References 39 publications

High CCR5 Density on Central Memory CD4+ T Cells in Acute HIV-1 Infection Is Mostly Associated with Rapid Disease Progression

High CCR5 Density on Central Memory CD4+ T Cells in Acute HIV-1 Infection Is Mostly Associated with Rapid Disease Progression

Lack of concordance between residual viremia and viral variants driving de novo infection of CD4+ T cells on ART

Analysis of Multiple Cell Reservoirs Expressing Unspliced HIV-1 gag-pol mRNA in Patients on Antiretroviral Therapy

Contact Info

Product

Resources

About