A5042546561- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Immune Cell Function and Interaction
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Biosensors and Analytical Detection
- Mosquito-borne diseases and control
- Virology and Viral Diseases
- Viral Infections and Immunology Research
- RNA Research and Splicing
- RNA regulation and disease
- Virus-based gene therapy research
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- Cellular transport and secretion
- Long-Term Effects of COVID-19
- Viral Infections and Outbreaks Research
- Complement system in diseases
- Bacteriophages and microbial interactions
- COVID-19 epidemiological studies
- Respiratory viral infections research
- COVID-19 Pandemic Impacts
King's College London
2016-2025
Guy's and St Thomas' NHS Foundation Trust
2023
Guy's Hospital
2012-2021
King's College School
2010-2018
University College London
1999-2011
Aaron Diamond AIDS Research Center
2006-2009
Rockefeller University
2006-2009
National Assembly
2004
Institute of Molecular Medicine
2003
Novartis (Austria)
1997-1998
Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10-15 d after the onset of COVID-19 symptoms. However, due recent emergence human population, it is not known how long antibody will maintained or whether they provide protection from reinfection. Using sequential serum samples collected up 94 post symptoms (POS) 65 with real-time quantitative PCR-confirmed infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) >95% cases and neutralizing when sampled...
The expression of many putative antiviral genes is upregulated when cells encounter type I interferon (IFN), but the actual mechanisms by which IFN-induced gene products inhibit virus replication are poorly understood. A recently identified antiretroviral protein, termed tetherin (previously known as BST-2 or CD317), blocks release nascent human immunodeficiency 1 (HIV-1) particles from infected cells, and an HIV-1 accessory Vpu, acts a viral antagonist tetherin. Here, we show that capable...
Abstract Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due recent emergence this virus human population it is not yet known how long these Ab will maintained or whether they provide protection from re-infection. Using sequential serum samples collected up 94 post symptoms (POS) 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion >95% cases and neutralizing antibody...
Recently proposed models that have gained wide acceptance posit HIV-1 virion morphogenesis is initiated by targeting the major structural protein (Gag) to late endosomal membranes. Thereafter, endosome-based secretory pathways are thought deliver Gag or assembled virions plasma membrane (PM) and extracellular milieu. We present several findings inconsistent with this model. Specifically, we demonstrate delivered PM, efficiently released into medium, when endosome motility abolished....
Tetherin/BST-2/CD317 is a recently identified antiviral protein that blocks the release of nascent retrovirus, and other virus, particles from infected cells. An HIV-1 accessory protein, Vpu, acts as an antagonist tetherin. Here, we show positive selection evident in primate tetherin sequences Vpu appears to have specifically adapted antagonize variants found humans chimpanzees. Tetherin rhesus macaques (rh), African green monkeys (agm) mice were able inhibit particle release, but resistant...
ABSTRACT Tetherin (CD317/BST-2), an interferon-induced membrane protein, restricts the release of nascent retroviral particles from infected cell surfaces. While human immunodeficiency virus type 1 (HIV-1) encodes accessory gene vpu to overcome action tetherin, lineage primate lentiviruses that gave rise HIV-2 does not. It has been previously reported envelope glycoprotein a Vpu-like function in promoting release. Here we demonstrate Rod (HIV-2 Env) is tetherin antagonist. Expression Env,...
Antiviral proteins that recognize pathogen-specific or aberrantly located molecular motifs are perfectly positioned to act as pattern-recognition receptors and signal the immune system. Here we investigated whether interferon-induced viral restriction factor tetherin (CD317/BST2), which is known inhibit HIV-1 particle release by physically tethering virions cell surface, has such a signaling role. We find upon of Vpu-defective HIV-1, acts virus sensor induce NFκB-dependent proinflammatory...
The cellular entry of severe acute respiratory syndrome-associated coronaviruses types 1 and 2 (SARS-CoV-1 -2) requires sequential protease processing the viral spike glycoprotein. presence a polybasic cleavage site in SARS-CoV-2 at S1/S2 boundary has been suggested to be factor increased transmissibility compared SARS-CoV-1 by facilitating maturation precursor furin-like proteases producer cells rather than endosomal cathepsins target. We investigate relevance route consequences this for...
Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with ACE2 on host cells is essential for viral entry. RBD dominant target neutralizing antibodies, and several epitopes have been molecularly characterized. Analysis circulating variants has revealed mutations arising in RBD, N-terminal (NTD) S2 subunits Spike. To understand how these affect antigenicity, we isolated characterized >100 monoclonal antibodies targeting NTD, from SARS-CoV-2-infected individuals. Approximately 45%...
SummaryBackgroundLateral flow devices (LFDs) for rapid antigen testing are set to become a cornerstone of SARS-CoV-2 mass community testing, although their reduced sensitivity compared with PCR has raised questions how well they identify infectious cases. Understanding capabilities and limitations is, therefore, essential successful implementation. We evaluated six commercial LFDs assessed correlation virus culture cycle threshold (Ct) values.MethodsIn single-centre, laboratory evaluation...
COVID-19 vaccine design and vaccination rollout need to take into account a detailed understanding of antibody durability cross-neutralizing potential against SARS-CoV-2 emerging variants concern (VOCs). Analyses convalescent sera provide unique insights longevity activity induced by variant spike proteins, which are putative candidates. Using from 38 individuals infected in wave 1, we show that can be detected up 305 days pos onset symptoms, although were less potent B.1.1.7 (Alpha) B1.351...
Epidemiological and whole-genome sequencing analysis of an ongoing outbreak Streptococcus pyogenes (Group A Streptococcus) in London (United Kingdom).
The human immunodeficiency virus (HIV) type-1 viral protein U (Vpu) enhances the release of diverse retroviruses from human, but not monkey, cells and is thought to do so by ablating a dominant restriction particle release. Here, we determined how Vpu expression affects subcellular distribution HIV-1 murine leukemia (MLV) Gag proteins in where is, or not, required for efficient In HeLa cells, MLV approximately 10-fold, concentrations fused cyan fluorescent (CFP) were initially detected at...
ABSTRACT Direct cell-to-cell spread of human immunodeficiency virus type 1 (HIV-1) between T cells at the virological synapse (VS) is an efficient mechanism viral dissemination. Tetherin (BST-2/CD317) interferon-induced, antiretroviral restriction factor that inhibits nascent cell-free particle release. The HIV-1 Vpu protein antagonizes tetherin activity; however, whether also restricts cell-cell unclear. We performed quantitative transfer analysis wild-type (WT) or Vpu-defective in Jurkat...
Critical cell surface immunoreceptors downregulated during HIV infection have previously been identified using non-systematic, candidate approaches. To gain a comprehensive, unbiased overview of how remodels the T surface, we took distinct, systems-level, quantitative proteomic approach. >100 plasma membrane proteins, many without characterized immune functions, were infection. Host factors targeted by viral accessory proteins Vpu or Nef included amino acid transporter SNAT1 and serine...
Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures inactivate tetherin, with prototype being HIV-1 Vpu protein. Here we show human herpesvirus Kaposi's sarcoma-associated (KSHV) sensitive to tetherin restriction and its activity counteracted by KSHV encoded RING-CH E3 ubiquitin ligase K5. expression in KSHV-infected cells particle release, as does depletion K5...