A5020111588- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- Lipid Membrane Structure and Behavior
- COVID-19 Clinical Research Studies
- interferon and immune responses
- T-cell and B-cell Immunology
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Cellular transport and secretion
- Viral gastroenteritis research and epidemiology
- HIV/AIDS Research and Interventions
- Long-Term Effects of COVID-19
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- T-cell and Retrovirus Studies
- Animal Virus Infections Studies
- HIV-related health complications and treatments
- vaccines and immunoinformatics approaches
- Herpesvirus Infections and Treatments
- Viral Infections and Outbreaks Research
Yale University
2016-2025
Yale Cancer Center
2021
Ludwig-Maximilians-Universität München
2018
Rush University Medical Center
2005
Salk Institute for Biological Studies
2005
Harvard University
1997-2002
Tufts University
2002
University of Würzburg
2002
Johannes Gutenberg University Mainz
2002
Howard Hughes Medical Institute
1998-2000
The HIV-1 envelope (Env) mediates viral entry into host cells. To enable the direct imaging of conformational dynamics within Env, we introduced fluorophores variable regions glycoprotein gp120 subunit and measured single-molecule fluorescence resonance energy transfer context native trimers on surface virions. Our observations revealed unliganded Env to be intrinsically dynamic, transitioning between three distinct prefusion conformations, whose relative occupancies were remodeled by...
Retroviral assembly and budding is driven by the Gag polyprotein requires host‐derived vacuolar protein sorting (vps) machinery. With exception of human immunodeficiency virus (HIV)‐infected macrophages, current models predict that vps machinery recruited to viral sites at cell surface. However, here we demonstrate HIV murine leukemia (MLV) also drive intracellularly in types including 293 HeLa cells, previously believed exclusively support from plasma membrane. Using live confocal...
Viruses have often been observed in association with the dense microvilli of polarized epithelia as well filopodia nonpolarized cells, yet whether interactions these structures contribute to infection has remained unknown. Here we show that virus binding induces a rapid and highly ordered lateral movement, "surfing" toward cell body before entry. Virus surfing along is mediated by underlying actin cytoskeleton depends on functional myosin II. Any disruption significantly reduces viral...
An antibody to block viral fusion A small fraction of HIV-1–infected individuals develop broad and potent antibodies that bind the HIV-1 envelope protein (Env). These recognize a limited set conserved epitopes on Env, such as Env's host receptor-binding site. Kong et al. now report neutralizing isolated from an individual binds peptide Env. This is unexpected because viruses often try mask key components their cell entry machinery attack. Crystal structures bound Env itself define epitope,...
Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement antibody therapies immunogen design. Here, we elucidate structural basis mode action two potent SARS-CoV-2 spike (S)-neutralizing monoclonal antibodies, CV3-1 CV3-25, which remain effective against emerging in vitro vivo. binds to (485-GFN-487) loop within receptor-binding...
Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector alone can protect Here, we isolated CV3-13, a non-neutralizing antibody, from convalescent individual with potent functions. The cryoelectron microscopy structure CV3-13 in complex the SARS-CoV-2 spike reveals antibody binds distinct angle approach an N-terminal domain (NTD) epitope only partially overlaps NTD...
SARS-CoV-2 surface S glycoprotein—the target of antibodies and vaccines—is responsible for binding to the cellular receptor hACE2. The interactions between hACE2 trigger structural rearrangements from closed open conformations prerequisite virus entry.
Cathepsins B and L are widely expressed cysteine proteases implicated in both intracellular proteolysis extracellular matrix remodeling. However, specific roles remain to be validated vivo . Here we show that combined deficiency of cathepsins mice is lethal during the second fourth week life. Cathepsin −/− /L reveal a degree brain atrophy not previously seen mice. This because massive apoptosis select neurons cerebral cortex cerebellar Purkinje granule cell layers. Neurodegeneration...
Retroviruses acquire a lipid envelope during budding from the membrane of their hosts. Therefore, composition this can provide important information about process and its location. Here, we present mass spectrometry analysis content human immunodeficiency virus type 1 (HIV-1) murine leukemia (MLV). The results comprehensive survey found that overall these viruses mostly matched plasma membrane, which was considerably different total cells. However, several lipids are enriched in comparison...