A5003808857- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- HIV/AIDS drug development and treatment
- vaccines and immunoinformatics approaches
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- HIV/AIDS Research and Interventions
- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Advanced Biosensing Techniques and Applications
- Genomics and Phylogenetic Studies
- Herpesvirus Infections and Treatments
- HIV-related health complications and treatments
- Complement system in diseases
- Mosquito-borne diseases and control
- Toxoplasma gondii Research Studies
- Molecular Biology Techniques and Applications
- Blood groups and transfusion
- Bacteriophages and microbial interactions
- Immunodeficiency and Autoimmune Disorders
VA San Diego Healthcare System
2015-2023
University of California, San Diego
2016-2023
10X Genomics (United States)
2022
University of California, Los Angeles
2014
LMU Klinikum
2011-2014
Ludwig-Maximilians-Universität München
2010-2013
Myeloid-derived suppressor cells (MDSCs) have been described as suppressors of T-cell functions in many tumor models. However, MDSC HIV-1 infection not studied to date. As impaired function is a hallmark chronic progressive infection, we hypothesized that also play role here.Surface staining and flow cytometry analysis were performed on freshly isolated peripheral blood mononuclear (PBMC) HIV-infected individuals compared healthy controls with lung carcinoma. late-stage using magnetic beads...
The VH1-2 restricted VRC01-class of antibodies targeting the HIV envelope CD4 binding site are a major focus vaccine strategies. However, detailed analysis antibody development has been limited by rare nature these responses during natural infection and lack longitudinal sampling such responses. To inform strategies, we mapped lineage (PCIN63) in subtype C infected IAVI Protocol neutralizer PC063. PCIN63 monoclonal had hallmark features demonstrated neutralization breadth similar to...
Abstract The vertebrate adaptive immune system modifies the genome of individual B cells to encode antibodies that bind particular antigens 1 . In most mammals, are composed heavy and light chains generated sequentially by recombination V, D (for chains), J C gene segments. Each chain contains three complementarity-determining regions (CDR1–CDR3), which contribute antigen specificity. Certain preferred for 2–22 Here we consider pairs share same V CDRH3 amino acid sequence were isolated from...
HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against infection. However, their elicitation is made difficult by low frequencies of appropriate precursor B cell receptors the complex maturation pathways required to generate bnAbs from these precursors. Antibody genes be engineered into cells for expression as both a functional antigen receptor on surfaces secreted antibody. Here, we show that bnAb-engineered primary mouse adoptively transferred vaccinated in...
Abstract The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies exceptional breadth. MPER usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some polyreactive, such 4E10. Here we describe an broadly antibody major IgG1 PGZL1, which shares V/D-region genes with 4E10, has a shorter CDRH3, is less polyreactive. A recombinant sublineage variant...
HIV reservoirs persist in anatomic compartments despite antiretroviral therapy (ART). Characterizing archival DNA the central nervous system (CNS) and other tissues is crucial to inform cure strategies. We evaluated paired autopsy brain-frontal cortex (FC), occipital (OCC), basal ganglia (BG)-and peripheral lymphoid from 63 people with HIV. Participants passed away while virally suppressed on ART at last visit without evidence of CNS opportunistic disease. quantified total all participants...
Molecular evolutionary arms races between viruses and their hosts are important drivers of adaptation. These Red Queen dynamics have been frequently observed in primate retroviruses antagonists, host restriction factor genes, such as APOBEC3F/G, TRIM5-α, SAMHD1, BST-2. Host factors experienced some the most intense pervasive adaptive evolution documented primates. Recently, two novel factors, SERINC3 SERINC5, were identified targets HIV-1 Nef, a protein crucial for optimal infectivity virus...
Long-read next-generation amplicon sequencing shows promise for studying complete genes or genomes from complex and diverse populations. Current long-read technologies have challenging error profiles, hindering data processing incorporation into downstream analyses. Here we consider the problem of how to reconstruct, free error, true sequence variants their associated frequencies PacBio reads. Called 'amplicon denoising', this has been extensively studied short-read technologies, but current...
Abstract Excessive immune activation is a hallmark of chronic uncontrolled HIV infection. During the past years, growing evidence suggests that inhibitory signals also play an important role in progressive disease. However, relationship between positive and negative on HIV‐specific CD8 T cells has not been studied detail so far HIV‐1 In this study, expression markers (CD38) (PD‐1) virus‐specific chronic, untreated infection was evaluated using intracellular cytokine staining. Viral escape...
Despite the major role of Gag in establishing resistance HIV-1 to protease inhibitors (PIs), very limited data are available on total contribution residues PIs. To identify detail and structural interfaces associated with development PIs, we traced viral evolution under pressure PIs using Gag-protease single genome sequencing coevolution analysis protein sequences 4 patients treated over a 9-year period. We identified 38 correlated protease, 32 which were outside cleavage sites. These...
Abstract Half a billion years of evolutionary battle forged the vertebrate adaptive immune system, an astonishingly versatile factory for molecules that can adapt to arbitrary attacks. The history individual encounter is chronicled within clonotype: descendants single fully rearranged cell. For B cells, reading this remains fundamental challenge modern immunology. Identification such clonotypes magnificently challenging problem three reasons: cell inferred rather than directly observed :...
HIV-1 Vpu decreases the exposure of epitopes within viral envelope glycoprotein (Env) on surface infected cells by downregulating both BST2 and CD4. To test hypothesis that inhibiting activity would increase these sensitize to antibody-dependent cellular cytotoxicity (ADCC), we treated with Nedd8 activation enzyme (NAE) inhibitor MLN4924, which inhibits cullin1-based ubiquitin ligase complex coopted degrade targets. Treatment HeLa MLN4924 or expression a dominant negative mutant cullin1...
The vertebrate adaptive immune system modifies the genome of individual B cells to encode antibodies binding particular antigens 1 . In most mammals, are composed a heavy and light chain which sequentially generated by recombination V, D (for chains), J, C gene segments. Each contains three complementarity-determining regions (CDR1-3), contributing antigen specificity. Certain chains preferred for 2–21 We considered pairs sharing same V CDRH3 amino acid sequence isolated from different...
Methods for identifying physiologically relevant CD8 T-cell epitopes are critically important not only the development of T-cell-based vaccines but also understanding host-pathogen interactions. As experimentally mapping an optimal epitope is a tedious procedure, many bioinformatic tools have been developed that predict which peptides bind to given MHC molecule. We assessed ability prediction syfpeithi, ctlpred and iedb foretell nine mapped HIV-specific epitopes. Randomly - any subjects' HLA...
HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against infection 1 . However, their elicitation is made difficult by low frequencies of appropriate precursor B cell receptors the complex maturation pathways required to generate bnAbs from these precursors 2 Antibody genes be engineered into cells for expression as both a functional receptor on surfaces secreted antibody 3–5 Here, we show that bnAb-engineered primary mouse adoptively transferred vaccinated in...
Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naïve precursors are hindered by unusual features that characterize these Abs, including insertions and deletions (indels). Longitudinal studies of natural HIV infection cases shed light on the complex processes underlying bnAb development have suggested a role for superinfection as potential enhancer neutralization breadth. Here we describe potent lineage was elicited two founder viruses to inform vaccine...
Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration combination antiretroviral therapy (ART). An exception to this scenario represented nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence ART. Several lines evidence indicate an important role T-cell response modulation infection during acute and chronic phase disease. We analyzed functional differentiation...
HIV evades CD8 T cell mediated pressure by viral escape mutations in targeted epitopes. A mutation can lead to a decline of the respective response. Our question was what happened after response and - case – if new towards mutated antigen could be generated population not selected for certain HLA alleles. We studied 19 antiretroviral-naïve HIV-1 infected individuals with different disease courses longitudinally. median number 12 (range 2-24) responses Gag Nef were detected per study subject....
To monitor the mitochondrial transmembrane potential (ΔΨm), peripheral blood mononuclear cells (PBMCs) from 18 HIV-uninfected individuals completing a 4-week course of HIV postexposure prophylaxis (PEP) with emtricitabine/tenofovir and lopinavir/ritonavir were analyzed. ΔΨm was assessed by FACS analysis after staining JC-1 using mixed effects regression analysis. Apoptosis determined Annexin-V-FITC propidium iodide staining. decreased significantly during HIV-PEP (p=0.0015 for linear term,...
Long-read next generation amplicon sequencing shows promise for studying complete genes or genomes from complex and diverse populations. Current long-read technologies have challenging error profiles, hindering data processing incorporation into downstream analyses. Here we consider the problem of how to reconstruct, free error, true sequence variants their associated frequencies. Called “amplicon denoising”, this has been extensively studied short-read technologies, but current solutions do...
ABSTRACT The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef is heavily targeted by CD8 + T lymphocytes (CTLs) during acute infection and therefore included in many candidate vaccines. We investigated whether CTL targeting of contributes to immune control disrupting the function Nef. sequence parallel with responses were assessed longitudinally from peak viremia until set point a cohort six subjects infection. All but one individual had single founder strain. Nef-specific...