A5068608033- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- HIV Research and Treatment
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- SARS-CoV-2 detection and testing
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- COVID-19 Impact on Reproduction
- Virus-based gene therapy research
- Malaria Research and Control
- Immunotherapy and Immune Responses
- Influenza Virus Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Virology and Viral Diseases
- Viral Infections and Immunology Research
- interferon and immune responses
- Fibromyalgia and Chronic Fatigue Syndrome Research
- COVID-19 epidemiological studies
- Long-Term Effects of COVID-19
Vitalant
2019-2024
University of California, San Francisco
2015-2024
Pacific Research Institute
2019-2024
University of Michigan
2024
Universidad Católica de Santa Fe
2023
Stanford University
2021
SLAC National Accelerator Laboratory
2021
University of California, Davis
2020
Louisiana State University Health Sciences Center New Orleans
2020
La Jolla Institute for Immunology
2020
Severe acute respiratory syndrome (SARS) is caused by an emergent coronavirus (SARS-CoV), for which there currently no effective treatment. SARS-CoV mediates receptor binding and entry its spike (S) glycoprotein, infection sensitive to lysosomotropic agents that perturb endosomal pH. We demonstrate here the lysosomotropic-agent-mediated block overcome protease treatment of target-cell-associated virus. In addition, was blocked specific inhibitors pH-sensitive cathepsin L. A cell-free...
The chemokine receptors CXCR4 and CCR5 have recently been shown to act as coreceptors, in concert with CD4, for human immunodeficiency virus–type 1 (HIV-1) infection. RANTES other chemokines that interact block infection of peripheral blood mononuclear cell cultures inhibit primary macrophages inefficiently at best. If used treat HIV-1–infected individuals, these could fail influence HIV replication nonlymphocyte compartments while promoting unwanted inflammatory side effects. A derivative...
Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a rapidly emerging pathogen with potentially serious consequences for public health. Here we describe conditions that result not only in the efficient expression of SARS-CoV spike (S) protein on surface cells, but its incorporation into lentiviral particles can be used to transduce cells an S glycoprotein-dependent manner. We found although some primate cell lines, including Vero E6, 293T and Huh-7 could efficiently...
The human coronaviruses (CoVs) severe acute respiratory syndrome (SARS)-CoV and NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown that recombinant SARS-CoV spike protein (SARS-S) downregulates ACE2 expression thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet unknown. We found SARS-S bound to induced shedding with higher efficiency than NL63-S. Shedding most likely accounted the previously observed downregulation but dispensable viral...
Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II. This protein displayed broader spectrum of receptor activities than any mammalian as it bound with high affinity to number both CC and CXC receptors. Binding vMIP-II, however, was not associated the normal, rapid mobilization calcium from intracellular stores; instead, blocked induced by endogenous chemokines. In freshly isolated human monocytes virally encoded vMIP-II acted potent efficient antagonist chemotaxis...
CCR5, a chemokine receptor expressed on T cells and macrophages, is the principal coreceptor for M-tropic HIV-1 strains. Recently, we described an NH2-terminal modification of CCR5 ligand regulated activation, normal cell secreted (RANTES), aminooxypentane-RANTES (AOP-RANTES), that showed potent inhibition macrophage infection by under conditions where RANTES was barely effective. To investigate mechanism AOP-RANTES HIV infectivity examined surface expression using monoclonal anti-CCR5...
The lectins DC-SIGN and DC-SIGNR can augment viral infection; however, the range of pathogens interacting with these attachment factors is incompletely defined. Here we show that enhance infection mediated by glycoprotein (GP) Marburg virus (MARV) S protein severe acute respiratory syndrome coronavirus might promote dissemination. SIGNR1, a murine homologue, also enhanced driven MARV Ebola GP could be targeted to assess role in filovirus vivo.
The novel human coronavirus EMC (hCoV-EMC), which recently emerged in Saudi Arabia, is highly pathogenic and could pose a significant threat to public health. elucidation of hCoV-EMC interactions with host cells critical our understanding the pathogenesis this virus identification targets for antiviral intervention. Here we investigated viral cellular determinants governing entry into cells. We found that spike protein (EMC-S) incorporated lentiviral particles mediates transduction cell...
The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) poses a constant threat to human health. viral spike protein (SARS-S) mediates host cell entry and is potential target for antiviral intervention. Activation of SARS-S by proteases essential SARS-CoV infectivity but remains incompletely understood. Here, we analyzed the role type II transmembrane serine (TTSPs) airway trypsin-like protease (HAT) protease, 2 (TMPRSS2), in activation. We found that HAT activates...
People who have been infected with or vaccinated against SARS-CoV-2 reduced risk of subsequent infection, but the proportion people in US antibodies from infection vaccination is uncertain.To estimate trends seroprevalence related to and population.In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations donations all 50 states; Washington, DC; Puerto Rico were organized into 66 study-specific regions, representing...
Abstract The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence infection. Serologic methods can more accurately estimate disease burden by detecting infections missed limited performed to date. Here, we describe validation coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, addition SARS-CoV,...
Abstract Given the limited availability of serological testing to date, seroprevalence SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 two San Francisco Bay Area populations. Seroreactivity was 0.26% 387 hospitalized patients admitted for non-respiratory indications and 0.1% 1,000 blood donors early April 2020. We additionally describe longitudinal dynamics immunoglobulin-G (IgG), immunoglobulin-M (IgM), vitro neutralizing...
Guanylate-binding protein (GBP) 5 is an interferon (IFN)-inducible cellular factor reducing HIV-1 infectivity by incompletely understood mechanism. Here, we show that this activity shared GBP2, but not other members of the human GBP family. GBP2/5 decrease proprotein convertase furin, which mediates conversion envelope (Env) precursor gp160 into mature gp120 and gp41. Because process primes Env for membrane fusion, viral particles produced in presence are poorly infectious due to increased...
A panel of primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates that infected several CD4+ T-cell lines, including MT-2 and C8166, were tested for infection blood-derived macrophages. Infectivity titers C8166 cells macrophages demonstrated SI strains much more efficiently than line-adapted HIV-1 such as LAI RF. These therefore dual-tropic. Nine biological clones two strains, prepared by limiting dilution, had macrophage/C8166 infectivity ratios similar to those their...
ABSTRACT The C-type lectins DC-SIGN and DC-SIGNR [collectively referred to as DC-SIGN(R)] bind transmit human immunodeficiency virus (HIV) simian T cells via the viral envelope glycoprotein (Env). Other viruses containing heavily glycosylated glycoproteins (GPs) fail interact with DC-SIGN(R), suggesting some degree of specificity in this interaction. We show here that DC-SIGN(R) selectively HIV Env Ebola GPs more high-mannose than complex carbohydrate structures. Modulation N -glycans on or...
We describe a small molecule chemokine receptor antagonist, UCB35625 (the trans-isomer J113863 published by Banyu Pharmaceutical Co., patent WO98/04554), which is potent, selective inhibitor of CCR1 and CCR3. Nanomolar concentrations were sufficient to inhibit eosinophil shape change responses MIP-1α, MCP-4, eotaxin, while greater could the chemokine-induced internalization both also inhibited CCR3-mediated entry human immunodeficiency virus-1 primary isolate 89.6 into glial cell line, NP-2...
Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with 2009 outbreak of 3 human cases acute hemorrhagic fever in Mangala village, Democratic Republic Congo (DRC), Africa. The cases, presenting over 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, two patients, death within days. BASV detected an serum sample from the lone survivor at concentration 1.09×106 RNA copies/mL, and 98.2% genome subsequently...
ABSTRACT The Ebola virus envelope glycoprotein (GP) derived from the pathogenic Zaire subtype mediates cell rounding and detachment extracellular matrix in 293T cells. In this study we provide evidence that GPs other subtypes, Sudan Côte d'Ivoire, as well Reston, a strain thought to be nonpathogenic humans, also induced rounding, albeit at lower levels than GP. Sequential removal of regions potential O-linked glycosylation C terminus GP1 led step-wise reduction without obviously affecting...
ABSTRACT Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died AIDS and neurological complications. Lymph node samples included for two the patients. Nineteen different clones patients distinct V1V2 sequences. Thirteen envelopes functional conferred fusigenicity infectivity CD4 + CCR5 cells. Infectivity cell-cell fusion assays showed that most used both CCR3. One brain-derived a broad range coreceptors, while three other one individual restricted...
Cellular cathepsins are required for Ebola virus infection and believed to proteolytically process the glycoprotein (GP) during entry. However, significance of cathepsin cleavage remains unclear. Here we demonstrate a role L (CatL) GP in generation stable 18-kDa GP1 viral intermediate that exhibits increased binding infectivity susceptible cell targets. Cell lymphocyte line was when CatL-proteolysed pseudovirions were used, but lymphocytes remained resistant GP-mediated infection. Genetic...