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Article ; Online: Differentiation of human cartilage degeneration by functional MRI mapping-an ex vivo study.

Truhn, Daniel / Sondern, Björn / Oehrl, Simon / Tingart, Markus / Knobe, Matthias / Merhof, Dorit / Kuhl, Christiane / Thüring, Johannes / Nebelung, Sven

European radiology

2019 Volume 29, Issue 12, Page(s) 6671–6681

Abstract: Objective: To evaluate whether the response to loading of cartilage samples as assessed ex vivo by quantitative MRI (qMRI) mapping techniques can differentiate intact and early degenerative cartilage.: Methods: Upon IRB approval and written informed ... ...

Abstract	Objective: To evaluate whether the response to loading of cartilage samples as assessed ex vivo by quantitative MRI (qMRI) mapping techniques can differentiate intact and early degenerative cartilage. Methods: Upon IRB approval and written informed consent, 59 macroscopically intact osteochondral samples were obtained from the central lateral femoral condyles of patients undergoing total knee replacement. Spatially resolved T1, T2, T2, and T1ρ maps were generated prior to and during displacement-controlled quasi-static indentation loading to 405 μm (Δ Results:* For T1ρ, consistent loading-induced increases were found for δ Conclusion: Aberrant load-bearing of early degenerative cartilage may be detected using T1ρ mapping as a function of loading. Hence, the diagnostic differentiation of intact versus early degenerative cartilage may allow the reliable identification of early and potentially reversible cartilage degeneration, thereby opening new opportunities for diagnosis and treatment of cartilage pathologies. Key points: • T1ρ mapping of the cartilage response to loading allows the reliable identification of early degenerative changes ex vivo. • Distinct response-to-loading patterns of cartilage tissue as assessed by functional MRI techniques are associated with biomechanical and histological tissue properties. • Non-invasive functional MR imaging techniques may facilitate the more sensitive monitoring of therapeutic outcomes and treatment strategies.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Cartilage Diseases/diagnosis ; Cartilage, Articular/pathology ; Female ; Humans ; Knee Joint/pathology ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged
Language	English
Publishing date	2019-06-11
Publishing country	Germany
Document type	Comparative Study ; Journal Article
ZDB-ID	1085366-2
ISSN	1432-1084 ; 0938-7994 ; 1613-3749
ISSN (online)	1432-1084
ISSN	0938-7994 ; 1613-3749
DOI	10.1007/s00330-019-06283-9
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Article ; Online: Generation of multi-millijoule red-shifted pulses for seeding stimulated Raman backscattering amplifiers.

Landgraf, Björn / Hoffmann, Andreas / Kartashov, Daniil / Gärtner, Felix / Samsonova, Zhanna / Polynkin, Pavel / Jacoby, Joachim / Kühl, Thomas / Spielmann, Christian

Optics express

2015 Volume 23, Issue 6, Page(s) 7400–7406

Abstract: The efficient generation of redshifted pulses from chirped femtosecond joule level Bessel beam pulses in gases is studied. The redshift spans from a few 100 cm⁻¹ to several 1000 cm⁻¹ corresponding to a shift of 50-500 nm for Nd:glass laser systems. The ... ...

Abstract	The efficient generation of redshifted pulses from chirped femtosecond joule level Bessel beam pulses in gases is studied. The redshift spans from a few 100 cm⁻¹ to several 1000 cm⁻¹ corresponding to a shift of 50-500 nm for Nd:glass laser systems. The generated pulses have an almost perfect Gaussian beam profile insensitive of the pump beam profile, and are much shorter than the pump pulses. The highest measured energy is as high as 30 mJ, which is significantly higher than possible with solid state nonlinear frequency shifters.
Language	English
Publishing date	2015-03-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	1491859-6
ISSN	1094-4087 ; 1094-4087
ISSN (online)	1094-4087
ISSN	1094-4087
DOI	10.1364/OE.23.007400
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Article ; Online: The viral protein Tat can inhibit the establishment of HIV-1 latency.

Donahue, Daniel A / Kuhl, Björn D / Sloan, Richard D / Wainberg, Mark A

Journal of virology

2012 Volume 86, Issue 6, Page(s) 3253–3263

Abstract: The establishment of HIV-1 latency can result from limiting levels of transcription initiation or elongation factors, restrictive chromatin modifications, transcriptional interference, and insufficient Tat activity. Since the viral protein Tat can ... ...

Abstract	The establishment of HIV-1 latency can result from limiting levels of transcription initiation or elongation factors, restrictive chromatin modifications, transcriptional interference, and insufficient Tat activity. Since the viral protein Tat can counteract many of these factors, we hypothesized that the presence of exogenous Tat during infection might inhibit the establishment of latency. This was explored using a Jurkat model of latency establishment and reactivation. PCR and reverse transcriptase PCR (RT-PCR) confirmed the latent state in this model and showed evidence of transcriptional interference. To address our hypothesis, cells undergoing infection were first exposed to either purified recombinant Tat or a transactivation-negative mutant. Only the former resulted in a modest inhibition of the establishment of latency. Next, Jurkat cells stably expressing intracellular Tat were used in our latency model to avoid limitations of Tat delivery. Experiments confirmed that intracellular Tat expression did not affect the susceptibility of these cells to viral infection. Eight weeks after infection, Jurkat cells expressing Tat harbored up to 1,700-fold fewer (P < 0.01) latent viruses than Jurkat cells that did not express Tat. Additionally, Tat delivered by a second virus was sufficient to reactivate most of the latent population. Our results suggest that inhibition of the establishment of latent infection is theoretically possible. In a hypothetical scenario of therapy that induces viral gene expression during acute infection, activation of viruses which would otherwise have entered latency could occur while concurrent highly active antiretroviral therapy (HAART) would prevent further viral spread, potentially decreasing the size of the established latent reservoir.
MeSH term(s)	Cell Line ; Down-Regulation ; Gene Expression Regulation, Viral ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/physiology ; Humans ; Virus Latency ; tat Gene Products, Human Immunodeficiency Virus/genetics ; tat Gene Products, Human Immunodeficiency Virus/metabolism
Chemical Substances	tat Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2012-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.06648-11
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Article ; Online: Treatment of children under 4 years of age with medulloblastoma and ependymoma in the HIT2000/HIT-REZ 2005 trials: Neuropsychological outcome 5 years after treatment.

Ottensmeier, Holger / Schlegel, Paul G / Eyrich, Matthias / Wolff, Johannes E / Juhnke, Björn-Ole / von Hoff, Katja / Frahsek, Stefanie / Schmidt, Rene / Faldum, Andreas / Fleischhack, Gudrun / von Bueren, Andre / Friedrich, Carsten / Resch, Anika / Warmuth-Metz, Monika / Krauss, Jürgen / Kortmann, Rolf D / Bode, Udo / Kühl, Joachim / Rutkowski, Stefan

PloS one

2020 Volume 15, Issue 1, Page(s) e0227693

Abstract: ... Diagnostics (WUEP-D), which includes Kaufman-Assessment-Battery, Coloured Progressive Matrices, Visual-Motor ...

Abstract	Young children with brain tumours are at high risk of developing treatment-related sequelae. We aimed to assess neuropsychological outcomes 5 years after treatment. This cross-sectional study included children under 4 years of age with medulloblastoma (MB) or ependymoma (EP) enrolled in the German brain tumour trials HIT2000 and HIT-REZ2005. Testing was performed using the validated Wuerzburg Intelligence Diagnostics (WUEP-D), which includes Kaufman-Assessment-Battery, Coloured Progressive Matrices, Visual-Motor Integration, finger tapping "Speed", and the Continuous Performance Test. Of 104 patients in 47 centres, 72 were eligible for analyses. We assessed whether IQ was impacted by disease extent, disease location, patient age, gender, age at surgery, and treatment (chemotherapy with our without craniospinal irradiation [CSI] or local radiotherapy [LRT]). Median age at surgery was 2.3 years. Testing was performed at a median of 4.9 years after surgery. Patients with infratentorial EPs (treated with LRT) scored highest in fluid intelligence (CPM 100.9±16.9, mean±SD); second best scores were achieved by patients with MB without metastasis treated with chemotherapy alone (CPM 93.9±13.2), followed by patients with supratentorial EPs treated with LRT. In contrast, lowest scores were achieved by patients that received chemotherapy and CSI, which included children with metastasised MB and those with relapsed MB M0 (CPM 71.7±8.0 and 73.2±21.8, respectively). Fine motor skills were reduced in all groups. Multivariable analysis revealed that type of treatment had an impact on IQ, but essentially not age at surgery, time since surgery or gender. Our results confirm previous reports on the detrimental effects of CSI in a larger cohort of children. Comparable IQ scores in children with MB treated only with chemotherapy and in children with EP suggest that this treatment strategy represents an attractive option for children who have a high chance to avoid application of CSI. Longitudinal follow-up examinations are warranted to assess long-term neuropsychological outcomes.
MeSH term(s)	Brain Neoplasms/pathology ; Brain Neoplasms/physiopathology ; Brain Neoplasms/therapy ; Child ; Child, Preschool ; Cohort Studies ; Combined Modality Therapy ; Craniospinal Irradiation/adverse effects ; Cross-Sectional Studies ; Ependymoma/pathology ; Ependymoma/physiopathology ; Ependymoma/therapy ; Female ; Follow-Up Studies ; Germany ; Humans ; Infant ; Intelligence ; Male ; Medulloblastoma/physiopathology ; Medulloblastoma/psychology ; Medulloblastoma/therapy ; Motor Skills ; Multivariate Analysis ; Neuropsychological Tests ; Treatment Outcome
Language	English
Publishing date	2020-01-23
Publishing country	United States
Document type	Clinical Trial ; Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0227693
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Article ; Online: Tetherin and its viral antagonists.

Kuhl, Björn D / Cheng, Vicky / Wainberg, Mark A / Liang, Chen

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2011 Volume 6, Issue 2, Page(s) 188–201

Abstract: Restriction factors comprise an important layer of host defense to fight against viral infection. Some restriction factors are constitutively expressed whereas the majority is induced by interferon to elicit innate immunity. In addition to a number of ... ...

Abstract	Restriction factors comprise an important layer of host defense to fight against viral infection. Some restriction factors are constitutively expressed whereas the majority is induced by interferon to elicit innate immunity. In addition to a number of well-characterized interferon-inducible antiviral factors such as RNaseL/OAS, ISG15, Mx, PKR, and ADAR, tetherin (BST-2/CD317/HM1.24) was recently discovered to block the release of enveloped viruses from the cell surface, which is regarded as a novel antiviral mechanism induced by interferon. Here, we briefly review the history of tetherin discovery, discuss how tetherin blocks virus production, and highlight the viral countermeasures to evade tetherin restriction.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antigens, CD/chemistry ; Antigens, CD/physiology ; Antiviral Agents/chemistry ; Antiviral Agents/metabolism ; Cell Membrane/chemistry ; Cell Membrane/metabolism ; Cell Membrane/virology ; GPI-Linked Proteins/antagonists & inhibitors ; GPI-Linked Proteins/chemistry ; GPI-Linked Proteins/physiology ; HIV-1/metabolism ; Humans ; Molecular Sequence Data ; Protein Binding/physiology ; Virion/physiology
Chemical Substances	Antigens, CD ; Antiviral Agents ; BST2 protein, human ; GPI-Linked Proteins
Language	English
Publishing date	2011-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-010-9256-1
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Article ; Online: Functional MR Imaging Mapping of Human Articular Cartilage Response to Loading.

Nebelung, Sven / Sondern, Björn / Oehrl, Simon / Tingart, Markus / Rath, Björn / Pufe, Thomas / Raith, Stefan / Fischer, Horst / Kuhl, Christiane / Jahr, Holger / Truhn, Daniel

Radiology

2017 Volume 282, Issue 2, Page(s) 464–474

Abstract: Purpose To determine if multiparametric magnetic resonance (MR) imaging mapping can be used to quantify the response to loading of histologically intact human knee cartilage. Materials and Methods Institutional review board approval and written informed ... ...

Abstract	Purpose To determine if multiparametric magnetic resonance (MR) imaging mapping can be used to quantify the response to loading of histologically intact human knee cartilage. Materials and Methods Institutional review board approval and written informed consent were obtained. Twenty macroscopically intact cartilage-bone samples were obtained from the central lateral femoral condyles in 11 patients undergoing total knee replacement. A clinical 3.0-T MR imaging system was used to generate T1, T1ρ, T2, and T2* maps with inversion recovery, spin-lock multiple gradient-echo, multiple spin-echo, and multiple gradient-echo sequences. Serial mapping was performed at three defined strain levels (strain 0 [δ
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Knee ; Biomechanical Phenomena ; Cartilage, Articular/diagnostic imaging ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Osteoarthritis, Knee/surgery ; Prospective Studies ; Weight-Bearing
Language	English
Publishing date	2017-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	80324-8
ISSN	1527-1315 ; 0033-8419
ISSN (online)	1527-1315
ISSN	0033-8419
DOI	10.1148/radiol.2016160053
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Article ; Online: Productive entry of HIV-1 during cell-to-cell transmission via dynamin-dependent endocytosis.

Sloan, Richard D / Kuhl, Björn D / Mesplède, Thibault / Münch, Jan / Donahue, Daniel A / Wainberg, Mark A

Journal of virology

2013 Volume 87, Issue 14, Page(s) 8110–8123

Abstract: HIV-1 can be transmitted as cell-free virus or via cell-to-cell contacts. Cell-to-cell transmission between CD4(+) T cells is the more efficient mode of transmission and is predominant in lymphoid tissue, where the majority of virus resides. Yet the ... ...

Abstract	HIV-1 can be transmitted as cell-free virus or via cell-to-cell contacts. Cell-to-cell transmission between CD4(+) T cells is the more efficient mode of transmission and is predominant in lymphoid tissue, where the majority of virus resides. Yet the cellular mechanisms underlying productive cell-to-cell transmission in uninfected target cells are unclear. Although it has been demonstrated that target cells can take up virus via endocytosis, definitive links between this process and productive infection remain undefined, and this route of transmission has been proposed to be nonproductive. Here, we report that productive cell-to-cell transmission can occur via endocytosis in a dynamin-dependent manner and is sensitive to clathrin-associated antagonists. These data were obtained in a number of CD4(+) T-cell lines and in primary CD4(+) T cells, using both CXCR4- and CCR5-tropic virus. However, we also found that HIV-1 demonstrated flexibility in its use of such endocytic pathways as certain allogeneic transmissions were seen to occur in a dynamin-dependent manner but were insensitive to clathrin-associated antagonists. Also, depleting cells of the clathrin accessory protein AP180 led to a viral uptake defect associated with enhanced infection. Collectively, these data demonstrate that endosomal uptake of HIV-1 during cell-to-cell transmission leads to productive infection, but they are also indicative of a flexible model of viral entry during cell-to-cell transmission, in which the virus can alter its entry route according to the pressures that it encounters.
MeSH term(s)	CD4-Positive T-Lymphocytes/virology ; Dynamins/metabolism ; Endocytosis/physiology ; HEK293 Cells ; HIV Infections/transmission ; HIV-1/physiology ; Humans ; Jurkat Cells ; Leukocytes, Mononuclear ; Models, Biological ; Monomeric Clathrin Assembly Proteins/deficiency ; RNA Interference ; Virus Internalization
Chemical Substances	Monomeric Clathrin Assembly Proteins ; clathrin assembly protein AP180 ; Dynamins (EC 3.6.5.5)
Language	English
Publishing date	2013-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00815-13
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Article ; Online: Treatment of children under 4 years of age with medulloblastoma and ependymoma in the HIT2000/HIT-REZ 2005 trials

Holger Ottensmeier / Paul G Schlegel / Matthias Eyrich / Johannes E Wolff / Björn-Ole Juhnke / Katja von Hoff / Stefanie Frahsek / Rene Schmidt / Andreas Faldum / Gudrun Fleischhack / Andre von Bueren / Carsten Friedrich / Anika Resch / Monika Warmuth-Metz / Jürgen Krauss / Rolf D Kortmann / Udo Bode / Joachim Kühl / Stefan Rutkowski

PLoS ONE, Vol 15, Iss 1, p e

Neuropsychological outcome 5 years after treatment.

2020 Volume 0227693

Abstract: ... Diagnostics (WUEP-D), which includes Kaufman-Assessment-Battery, Coloured Progressive Matrices, Visual-Motor ...

Abstract	Young children with brain tumours are at high risk of developing treatment-related sequelae. We aimed to assess neuropsychological outcomes 5 years after treatment. This cross-sectional study included children under 4 years of age with medulloblastoma (MB) or ependymoma (EP) enrolled in the German brain tumour trials HIT2000 and HIT-REZ2005. Testing was performed using the validated Wuerzburg Intelligence Diagnostics (WUEP-D), which includes Kaufman-Assessment-Battery, Coloured Progressive Matrices, Visual-Motor Integration, finger tapping "Speed", and the Continuous Performance Test. Of 104 patients in 47 centres, 72 were eligible for analyses. We assessed whether IQ was impacted by disease extent, disease location, patient age, gender, age at surgery, and treatment (chemotherapy with our without craniospinal irradiation [CSI] or local radiotherapy [LRT]). Median age at surgery was 2.3 years. Testing was performed at a median of 4.9 years after surgery. Patients with infratentorial EPs (treated with LRT) scored highest in fluid intelligence (CPM 100.9±16.9, mean±SD); second best scores were achieved by patients with MB without metastasis treated with chemotherapy alone (CPM 93.9±13.2), followed by patients with supratentorial EPs treated with LRT. In contrast, lowest scores were achieved by patients that received chemotherapy and CSI, which included children with metastasised MB and those with relapsed MB M0 (CPM 71.7±8.0 and 73.2±21.8, respectively). Fine motor skills were reduced in all groups. Multivariable analysis revealed that type of treatment had an impact on IQ, but essentially not age at surgery, time since surgery or gender. Our results confirm previous reports on the detrimental effects of CSI in a larger cohort of children. Comparable IQ scores in children with MB treated only with chemotherapy and in children with EP suggest that this treatment strategy represents an attractive option for children who have a high chance to avoid application of CSI. Longitudinal follow-up examinations are warranted to assess long-term neuropsychological outcomes.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: SorCS1 variants and amyloid precursor protein (APP) are co-transported in neurons but only SorCS1c modulates anterograde APP transport.

Hermey, Guido / Schmidt, Nadine / Bluhm, Björn / Mensching, Daniel / Ostermann, Kristina / Rupp, Carsten / Kuhl, Dietmar / Kins, Stefan

Journal of neurochemistry

2015 Volume 135, Issue 1, Page(s) 60–75

Abstract: Processing of amyloid precursor protein (APP) into amyloid-β peptide (Aβ) is crucial for the development of Alzheimer's disease (AD). Because this processing is highly dependent on its intracellular itinerary, altered subcellular targeting of APP is ... ...

Abstract	Processing of amyloid precursor protein (APP) into amyloid-β peptide (Aβ) is crucial for the development of Alzheimer's disease (AD). Because this processing is highly dependent on its intracellular itinerary, altered subcellular targeting of APP is thought to directly affect the degree to which Aβ is generated. The sorting receptor SorCS1 has been genetically linked to AD, but the underlying molecular mechanisms are poorly understood. We analyze two SorCS1 variants; one, SorCS1c, conveys internalization of surface-bound ligands whereas the other, SorCS1b, does not. In agreement with previous studies, we demonstrate co-immunoprecipitation and co-localization of both SorCS1 variants with APP. Our results suggest that SorCS1c and APP are internalized independently, although they mostly share a common post-endocytic pathway. We introduce functional Venus-tagged constructs to study SorCS1b and SorCS1c in living cells. Both variants are transported by fast anterograde axonal transport machinery and about 30% of anterograde APP-positive transport vesicles contain SorCS1. Co-expression of SorCS1b caused no change of APP transport kinetics, but SorCS1c reduced the anterograde transport rate of APP and increased the number of APP-positive stationary vesicles. These data suggest that SorCS1 and APP share trafficking pathways and that SorCS1c can retain APP from insertion into anterograde transport vesicles. Altered APP trafficking is thought to modulate its processing. SorCS1 has been suggested to function in APP trafficking. We analyzed if the two SorCS1 variants, SorCS1b and SorCS1c, tie APP to the cell surface or modify its internalization and intracellular targeting. We observed co-localization and vesicular co-transport of APP and SorCS1, but independent internalization and sorting through a common post-endocytic pathway. Co-expression of one variant, SorCS1c, reduced anterograde APP transport. These data demonstrate that SorCS1 and APP share trafficking pathways and that SorCS1c can retain APP from insertion into anterograde transport vesicles.
MeSH term(s)	Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Cytoplasm/metabolism ; Mice ; Neurons/metabolism ; Protein Transport/physiology ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Symporters/metabolism
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Receptors, Cell Surface ; SORCS1 protein, mouse ; Symporters
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.13221
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Article ; Online: Association of HLA-DRB1-restricted CD4⁺ T cell responses with HIV immune control.

Ranasinghe, Srinika / Cutler, Sam / Davis, Isaiah / Lu, Richard / Soghoian, Damien Z / Qi, Ying / Sidney, John / Kranias, Gregory / Flanders, Michael D / Lindqvist, Madelene / Kuhl, Bjorn / Alter, Galit / Deeks, Steven G / Walker, Bruce D / Gao, Xiaojiang / Sette, Alessandro / Carrington, Mary / Streeck, Hendrik

Nature medicine

2013 Volume 19, Issue 7, Page(s) 930–933

Abstract: The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated previously uncharacterized peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 ... ...

Abstract	The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated previously uncharacterized peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and progressors. We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with HLA-DRB115:02 significantly associated with low viremia and HLA-DRB103:01 significantly associated with high viremia. Notably, a subgroup of HLA-DRB1 variants linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 variants linked with high viremia. Our data provide systematic evidence that HLA-DRB1 variant expression has a considerable impact on the control of HIV replication, an effect that seems to be mediated primarily by the protein specificity of CD4(+) T cell responses to HIV Gag and Nef.
MeSH term(s)	Alleles ; CD4-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Cohort Studies ; Disease Resistance/genetics ; Disease Resistance/immunology ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; HIV Infections/blood ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/immunology ; HIV-1/physiology ; HLA-DRB1 Chains/genetics ; HLA-DRB1 Chains/immunology ; HLA-DRB1 Chains/metabolism ; Humans ; Viral Load/genetics ; Viral Load/physiology ; Virus Replication/genetics ; Virus Replication/immunology
Chemical Substances	HLA-DRB1 Chains
Language	English
Publishing date	2013-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm.3229
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