A5090719481- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
- Viral Infections and Outbreaks Research
- HIV/AIDS drug development and treatment
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- Mosquito-borne diseases and control
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- Complement system in diseases
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Erythrocyte Function and Pathophysiology
- Lipid Membrane Structure and Behavior
- Disaster Response and Management
- Infectious Encephalopathies and Encephalitis
- Phagocytosis and Immune Regulation
- Malaria Research and Control
- SARS-CoV-2 detection and testing
Harvard University
2008-2025
Boston Children's Hospital
2007-2025
Boston Children's Museum
2023-2024
Scripps Research Institute
2015-2024
The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
2024
University of Florida
2004-2023
Scripps (United States)
2022
Scripps Institution of Oceanography
2022
Harvard University Press
2013
Jeonbuk National University
2010
Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection their target cells. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS (SARS-CoV)-permissive Vero E6 cells, efficiently binds S1 domain SARS-CoV S protein. We found soluble form ACE2, but not related ACE1, blocked association 293T cells transfected those human immunodeficiency...
SARS-CoV-2 variants with spike (S)-protein D614G mutations now predominate globally. We therefore compare the properties of mutated S protein (SG614) original (SD614). report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than those SD614. This increased entry correlates less S1-domain shedding and higher S-protein incorporation into virion. Similar results are obtained virus-like particles produced M, N, E, proteins. However, does not alter binding to ACE2 or...
The coronavirus spike (S) protein mediates infection of receptor-expressing host cells and is a critical target for antiviral neutralizing antibodies. Angiotensin-converting enzyme 2 (ACE2) functional receptor the (severe acute respiratory syndrome (SARS)-CoV) that causes SARS. Here we demonstrate 193-amino acid fragment S (residues 318–510) bound ACE2 more efficiently than did full S1 domain 12–672). Smaller fragments, expressing residues 327–510 or 318–490, not detectably bind ACE2. A...
Chemokine receptors serve as coreceptors for HIV entry into CD4+ cells. Their expression is thought to determine the tropism of viral strains different cell types, and also influence susceptibility infection rates disease progression. Of chemokine receptors, CCR5 most important transmission, since principal receptor primary, macrophage-tropic viruses, individuals homozygous a defective allele (Δ32/ Δ32) are highly resistant with HIV-1. In this study, CCR5-specific mAbs were generated using...
ABSTRACT SARS coronavirus 2 (SARS-CoV-2) isolates encoding a D614G mutation in the viral spike (S) protein predominate over time locales where it is found, implying that this change enhances transmission. We therefore compared functional properties of S proteins with aspartic acid (S D614 ) and glycine G614 at residue 614. observed retroviruses pseudotyped infected ACE2-expressing cells markedly more efficiently than those . This greater infectivity was correlated less S1 shedding...
Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show IFITM restricted entry glycoproteins (GP1,2) of Marburg Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically filovirus IAV processes. also inhibited replication infectious MARV EBOV. We observed distinct patterns IFITM-mediated...
Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence highly contagious often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against S1 domain spike (S) protein SARS-CoV from two nonimmune antibody libraries. One scFv 80R efficiently neutralized inhibited syncytia formation between cells expressing S those receptor...
Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human NL63 (HCoV-NL63). In addition hostcell receptors, lysosomal cysteine proteases are required productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of protease cathepsin L ACE2-expressing Inhibitors blocked SARS-CoV retrovirus...
Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus Ebola an entry factor dengue virus. Here we show that promotes infection of retroviruses virus-like particles (VLPs) pseudotyped with range viral proteins, in particular those from the filovirus, flavivirus, New World arenavirus alphavirus families. also robustly enhanced replication-competent...
Hydroxychloroquine, used to treat malaria and some autoimmune disorders, potently inhibits viral infection of SARS coronavirus (SARS-CoV-1) SARS-CoV-2 in cell-culture studies. However, human clinical trials hydroxychloroquine failed establish its usefulness as treatment for COVID-19. This compound is known interfere with endosomal acidification necessary the proteolytic activity cathepsins. Following receptor binding endocytosis, cathepsin L can cleave SARS-CoV-1 spike (S) proteins, thereby...
Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, the closely related dengue (DENV) or West Nile (WNV), can efficiently infect key placental barrier cells directly contact fetal bloodstream. We AXL, receptor tyrosine kinase, is primary ZIKV entry cofactor on human umbilical vein endothelial...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme (ACE2). ACE2 is also the viral receptor SARS-CoV (SARS-CoV-1), a related that emerged in 2002–2003. Horseshoe bats (genus Rhinolophus ) are presumed to be original reservoir both viruses, and SARS-like coronavirus, RaTG13, closely SARS-CoV-2, has been identified one horseshoe-bat species. Here we characterize ability S-protein...
Abstract During the COVID-19 pandemic, Pfizer-BioNTech and Moderna successfully developed nucleoside-modified mRNA lipid nanoparticle (LNP) vaccines. SARS-CoV-2 spike protein expressed by those vaccines are identical in amino acid sequence, but several key components distinct. Here, we compared effect of ionizable lipids, untranslated regions (UTRs), nucleotide composition two vaccines, focusing on delivery, antibody generation, long-term stability. We found that lipid, SM-102, Moderna’s...
Production of amyloid-beta protein (Abeta) is initiated by a beta-secretase that cleaves the Abeta precursor (APP) at N terminus (the beta site). A recently identified aspartyl protease, BACE, site and residue 11 within region APP. Here we show BACE2, BACE homolog, more efficiently different Abeta. The Flemish missense mutation APP, implicated in form familial Alzheimer's disease, adjacent to this latter markedly increases production BACE2 but not BACE. respond identically conservative...
Clinical isolates of primate immunodeficiency viruses, including human virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor CCR5, a member seven-transmembrane family. HIV-1 variants which use additional receptors are present in central nervous system or emerge during course infection. Simian viruses (SIV) have been shown CCR5 as coreceptor, but no other for these identified. Here we show that two orphan segment receptors, gpr1 gpr15, serve...