A5069929676- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- Bacterial Infections and Vaccines
- Cytomegalovirus and herpesvirus research
- Respiratory viral infections research
- Herpesvirus Infections and Treatments
- Cytokine Signaling Pathways and Interactions
- Cellular transport and secretion
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Cancer-related molecular mechanisms research
- Immune Response and Inflammation
- Photoreceptor and optogenetics research
- RNA Research and Splicing
- Hepatitis B Virus Studies
- Helicobacter pylori-related gastroenterology studies
- HER2/EGFR in Cancer Research
- SARS-CoV-2 and COVID-19 Research
- Metastasis and carcinoma case studies
- Hormonal Regulation and Hypertension
Aintree University Hospital
2024
University of Liverpool
2024
Ragon Institute of MGH, MIT and Harvard
2011-2020
Harvard University
2009-2020
University of Bonn
2017
Hospital for Special Surgery
2015
Centre Hospitalier Universitaire de Caen Normandie
1988-2013
Université de Caen Normandie
1993-2013
Klinikum Oldenburg
2013
Massachusetts General Hospital
2004-2009
Getting HIV Under Control Approximately 1 in 300 people infected with are “controllers” who able to maintain long-term control of the virus without medication and do not progress AIDS. Uncovering genetic basis for this ability is great interest. Pereyra et al. (p. 1551 , published online 4 November; see Perspective by McMichael Jones ) now present genome-wide association results from patients enrolled International Controllers Study. The analysis compared controllers European,...
Ligation of CCR5 by the CC chemokines RANTES, MIP-1α or MIP-1β, and CXCR4 CXC chemokine SDF-1α, profoundly inhibits replication HIV strains that use these coreceptors for entry into CD4+ T lymphocytes. The mechanism inhibition is not known. We found a rapid extensive downregulation SDF-1α RANTES antagonist RANTES(9-68). Confocal laser scanning microscopy showed CXCR4, after binding to their ligands, are internalized vesicles qualify as early endosomes indicated colocalization with...
ABSTRACT Human leukocyte antigen (HLA)-B27-positive subjects are uncommon in their ability to control infection with human immunodeficiency virus type 1 (HIV-1). However, late viral escape from a narrowly directed immunodominant Gag-specific CD8 + T-lymphocyte (CTL) response has been linked AIDS progression these individuals. Identifying the mechanism of immune-mediated may provide critical insights into HIV-1 vaccine development. Here, we illustrate that CTL mutation R 264 K...
Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more upon TLR7 stimulation than pDCs males, yet mechanisms underlying this difference remain unclear. In article, we show that basal levels IFN regulatory factor (IRF) 5 in were significantly higher compared with males positively correlated percentage IFN-α-secreting pDCs. Delivery recombinant IRF5 protein into human primary increased...
Mutations within cytotoxic T lymphocyte (CTL) epitopes impair cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined natural human infections. In histocompatibility leukocyte (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine proline at Gag residue 146 immediately preceding the NH2 terminus of dominant HLA-B57–restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides...
HIV-1-infected cells can avoid cytotoxic T lymphocyte killing by Nef-mediated down-regulation of surface MHC I. Here, we show that HIV-1 Nef inhibits II restricted peptide presentation to specific and thus may affect the induction antiviral immune responses. mediates this effect reducing level mature (i.e., peptide-loaded) while increasing levels immature II, which are functionally incompetent because their association with invariant chain. was only gene product possess capacity, also...
Numerous studies now support that human immunodeficiency virus type 1 (HIV-1) evolution is influenced by immune selection pressure, with population showing an association between specific HLA alleles and mutations within defined cytotoxic T-lymphocyte epitopes. Here we combine sequence data functional of CD8 T-cell responses to demonstrate allele-specific pressures also select for flanking epitopes impair antigen processing. In persons expressing HLA-A3, consistent a mutation in C-terminal...
Human immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. The associations most frequently observed are between an HLA molecule variation from the consensus sequence. However, a substantial number have been identified in which particular allele is preservation mechanism behind this so far...
Human lymphocyte antigen (HLA)-restricted CD8+ cytotoxic T lymphocytes (CTL) target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish replication fitness. Here, we assess the fitness impact of emerging in seven gp120 Env p24 Gag coding regions an individual followed longitudinally from time acute HIV-1 infection, as well some these same recognized other HIV-1-infected individuals. Nine dominant...
Anaesthesia for medical purposes was introduced in the 19th century. However, physiological mode of anaesthetic drug actions on nervous system remains unclear. One remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as noble gas xenon, act agents inducing loss consciousness. The main goal here to determine if anaesthetics affect same or similar processes plants animals humans.
Major histocompatibility class I (MHC-I)-specific inhibitory receptors on natural killer (NK) cells (iNKRs) tolerize mature NK cell responses toward normal cells. generate cytolytic to virus-infected or malignant target with altered decreased MHC-I surface expression due the loss of tolerizing ligands. The NKG2A/CD94 iNKR suppresses through recognition non-classical MHC-I, HLA-E. We used HIV-infected primary T-cells as targets in an vitro assay autologous from healthy donors. In these...
Abstract Antitumor T-cell responses have the potential to be curative in cancer patients, but induction of potent immunity through vaccination remains a largely unmet goal immunotherapy. We previously reported that immunogenicity peptide vaccines could increased by maximizing delivery lymph nodes (LNs), where are generated. This was achieved conjugating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG (DSPE-PEG) promote albumin binding, which resulted enhanced lymphatic drainage and...
The lumen of the endoplasmic reticulum (ER) differs from cytosol in its content ions and other small molecules, but it is unclear whether ER membrane as impermeable membranes cell. Here, we have tested permeability to small, nonphysiological molecules. We report that isolated vesicles allow different chemical modification reagents pass outside into with little hindrance. In permeabilized cells, allows passage a charged reagent unable cross plasma or lysosomal trans-Golgi membranes. A larger...
Peptide presentation is critical for immune recognition of pathogen-infected cells by CD8+ T lymphocytes. Although a limited number immunodominant peptide epitopes are consistently observed in diseases such as HIV-1 infection, the relationship between immunodominance and antigen processing humans largely unknown. Here, we have demonstrated that endogenous human epitope more efficient than subdominant epitope. Furthermore, shown regions flanking constitute portable motif increases production...
ABSTRACT Nef is a myristoylated protein of 27 to 35 kDa that conserved in primate lentiviruses. In vivo, required for high viral load and full pathological effects. vitro, has at least four activities: induction CD4 major histocompatibility complex (MHC) class I downregulation, enhancement infectivity, alteration T-cell activation pathways. We previously reported the from human immunodeficiency virus type 1 interacts with novel thioesterase (hTE). present study, by mutational analysis, we...
The human immunodeficiency virus type 1 Nef protein alters the post-Golgi stages of major histocompatibility complex class I (MHC-I) biogenesis. Presumed mechanisms involve disclosure a cryptic tyrosine-based sorting signal (YSQA) located in cytoplasmic tail HLA-A and -B heavy chains. We changed this for prototypic motif (YSQI or YSQL). Modified HLA-A2 molecules, termed A2-endo, displayed constitutively low surface levels accumulated region close to within Golgi apparatus, behavior...
Nef is a 27-kDa myristoylated protein conserved in primate lentiviruses. In vivo, simian immunodeficiency virus required macaques to produce high viral load and full pathological effects. has at least three major effects vitro, induction of CD4 down-regulation, alteration T cell activation pathways, enhancement infectivity. We have used the yeast two-hybrid system identify cellular proteins that interact with HIV-1Lai could mediate function. A human cDNA was isolated encodes new type...