A5069485745- HIV Research and Treatment
- Genomics and Rare Diseases
- HIV/AIDS drug development and treatment
- Genetic Associations and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Respiratory viral infections research
- COVID-19 Clinical Research Studies
- HIV/AIDS Research and Interventions
- CRISPR and Genetic Engineering
- vaccines and immunoinformatics approaches
- Hepatitis C virus research
- Animal Virus Infections Studies
- Influenza Virus Research Studies
- Immunodeficiency and Autoimmune Disorders
- RNA modifications and cancer
- Evolution and Genetic Dynamics
- Viral Infections and Immunology Research
- T-cell and B-cell Immunology
- interferon and immune responses
- Long-Term Effects of COVID-19
- Genomic variations and chromosomal abnormalities
VIR Biotechnology (United States)
2020-2025
Vir Biotechnology (Switzerland)
2020-2025
École Polytechnique Fédérale de Lausanne
2011-2023
University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca
2019
Human Longevity (United States)
2016-2018
SIB Swiss Institute of Bioinformatics
2013-2018
University Hospital of Lausanne
2013-2014
University of Debrecen
2014
Czech Academy of Sciences, Institute of Microbiology
2013
Hungarian Academy of Sciences
2013
Targeting a range of betacoranaviruses In the past 20 years, three highly pathogenic β-coronaviruses have crossed from animals to humans, including most recent: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A spike protein that decorates these viruses has an S1 domain binds host cell receptors and S2 fuses viral membranes allow entry. The is target many neutralizing antibodies but more genetically variable than S2, can exert selective pressure, leading resistant variants....
HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data 1071 individuals, we ran >3000 genome-wide scans, testing for associations between DNA polymorphisms, variation plasma load (VL), while considering population structure. We observed significant SNP to a total of 48 amino acid variants (p<2.4 × 10(-12)). All associated SNPs mapped the HLA class I region. Clinical relevance pathogen was assessed using VL results....
SARS-CoV-2 evolution threatens vaccine- and natural infection-derived immunity as well the efficacy of therapeutic antibodies. To improve public health preparedness, we sought to predict which existing amino acid mutations in might contribute future variants concern. We tested predictive value features comprising epidemiology, evolution, immunology, neural network-based protein sequence modeling, identified primary biological drivers intra-pandemic evolution. found evidence that...
Rapidly evolving influenza A viruses (IAVs) and B (IBVs) are major causes of recurrent lower respiratory tract infections. Current vaccines elicit antibodies predominantly to the highly variable head region haemagglutinin their effectiveness is limited by viral drift1 suboptimal immune responses2. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits enzymatic activity all group 1 2 IAVs, as well Victoria/2/87-like, Yamagata/16/88-like ancestral IBVs....
Significance A proportion of the variation in HIV-1 viral load infected population is influenced by host genetics. Using a large sample individuals ( n = 6,315) with genome-wide genotype data, we sought to map genomic regions that influence HIV and quantify their impact. We identified amino acid positions located binding groove class I HLA proteins (HLA-A -B) SNPs chemokine (C-C motif) receptor 5 gene region together explain 14.5% observed load. Controlling for these signals, estimated an...
HIV-1 infects CD4+ T cells and completes its replication cycle in approximately 24 hours. We employed repeated measurements a standardized cell system rigorous mathematical modeling to characterize the emergence of viral intermediates their impact on cellular transcriptional response with high temporal resolution. observed 7,991 (73%) 10,958 expressed genes be modulated concordance key steps replication. Fifty-two percent overall variability host transcriptome was explained by linear...
Significance Life-threatening susceptibility to common respiratory infections in previously healthy children can be indicative of pathogen-specific primary immunodeficiencies due rare deleterious variants key genes and pathways the immune system. These findings have implications for prevention treatment susceptible children.
Reducing premature mortality associated with age-related chronic diseases, such as cancer and cardiovascular disease, is an urgent priority. We report early results using genomics in combination advanced imaging other clinical testing to proactively screen for disease risk among adults. enrolled active, symptom-free adults a study of screening diseases mortality. In addition personal family medical history testing, we obtained whole-genome sequencing (WGS), noncontrast whole-body MRI,...
HIV latency is a major obstacle to curing infection. Current strategies eradicate aim at increasing transcription of the latent provirus. In present study we observed that latently infected CD4+ T cells from HIV-infected individuals failed produce viral particles upon ex vivo exposure SAHA (vorinostat), despite effective inhibition histone deacetylases. To identify steps were not susceptible action or other reverting agents, used primary cell model, joint host and RNA sequencing,...
The magnitude of the human antibody response to viral antigens is highly variable. To explore genetic contribution this variability, we performed genome-wide association studies immunoglobulin G 14 pathogenic viruses in 2,363 immunocompetent adults. Significant associations were observed major histocompatibility complex region on chromosome 6 for influenza A virus, Epstein-Barr JC polyomavirus, and Merkel cell polyomavirus. Using local imputation fine mapping, identified specific amino acid...
Abstract Background The HIV-1 genome is subject to pressures that target the virus resulting in escape and adaptation. On other hand, there a requirement for sequence conservation because of functional structural constraints. Mapping sites selective pressure on viral generates reference understanding limits escape, can serve as template discovery genetic conflict with known or unknown host proteins. Results To build thorough evolutionary, map genome, complete subtype B sequences were...
Abstract The 20 residue long Trp‐cage is the smallest protein known, and thus has been subject of several in vitro silico folding studies. Here, we report multistate scenario miniprotein atomic detail. We detected characterized different intermediate states by temperature dependent NMR measurements 15 N 13 C/ labeled protein, both at neutral acidic pH values. developed a deconvolution technique to characterize invisible—fully folded, unfolded intermediate—fast exchanging states. Using...
PurposeThe implementation of genomic-based medicine is hindered by unresolved questions regarding data privacy and delivery interpreted results to health-care practitioners. We used DNA-based prediction HIV-related outcomes as a model explore critical issues in clinical genomics.MethodsWe genotyped 4,149 markers HIV-positive individuals. Variants allowed for 17 traits relevant HIV medical care, inference patient ancestry, imputation human leukocyte antigen (HLA) types. Genetic were processed...
Sequence variation data of the human proteome can be used to analyze 3D protein structures derive functional insights. We genetic variant from nearly 140,000 individuals positional conservation in 4,715 proteins and 3,951 homology models using 860,292 missense 465,886 synonymous variants. Sixty percent harbor at least one intolerant site as defined by significant depletion observed over expected variation. Structural intolerance correlated with deep mutational scanning readouts for PPARG,...
Loss-of-function variants in innate immunity genes are associated with Mendelian disorders the form of primary immunodeficiencies. Recent resequencing projects report that stop-gains and frameshifts collectively prevalent humans could be responsible for some inter-individual variability immune response. Current computational approaches evaluating loss-of-function carrying these rely on gene-level characteristics such as evolutionary conservation functional redundancy across genome. However,...
Sequencing projects have identified large numbers of rare stop-gain and frameshift variants in the human genome. As most these are observed heterozygous state, they test a gene’s tolerance to haploinsufficiency dominant loss function. We analyzed distribution truncating across 16,260 autosomal protein coding genes 11,546 individuals. 39,893 affecting 12,062 genes, which significantly differed from an expectation 12,916 under model neutral de novo mutation (p<10−4). Extrapolating this...
Abstract SARS-CoV-2 evolution threatens vaccine- and natural infection-derived immunity, the efficacy of therapeutic antibodies. Herein we sought to predict Spike amino acid changes that could contribute future variants concern. We tested importance features comprising epidemiology, evolution, immunology, neural network-based protein sequence modeling. This resulted in identification primary biological drivers intra-pandemic evolution. found evidence resistance population-level host immunity...
The recent emergence of SARS-CoV-2 variants concern (VOC) and the recurrent spillovers coronaviruses in human population highlight need for broadly neutralizing antibodies that are not affected by ongoing antigenic drift can prevent or treat future zoonotic infections. Here, we describe a monoclonal antibody (mAb), designated S2X259, recognizing highly conserved cryptic receptor-binding domain (RBD) epitope cross-reacting with spikes from all sarbecovirus clades. S2X259 neutralizes...