A5089854130- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Long-Term Effects of COVID-19
- HIV Research and Treatment
- RNA regulation and disease
- Immune Response and Inflammation
- Immune cells in cancer
- RNA Research and Splicing
- Animal Virus Infections Studies
- Phagocytosis and Immune Regulation
- Viral gastroenteritis research and epidemiology
King's College London
2020-2024
University College London
2019-2020
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...
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...
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%...
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...
The appearance of new dominant variants concern (VOC) severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) threatens the global response to disease 2019 (COVID-19) pandemic. Of these, alpha variant (also known as B.1.1.7), which appeared initially in United Kingdom, became much Europe and North America first half 2021. spike (S) glycoprotein acquired seven mutations two deletions compared ancestral virus, including P681H mutation adjacent polybasic cleavage site, has been...
Macrophages exist predominantly in two distinct states, G0 and a G1-like state that is accompanied by phosphorylation of SAMHD1 at T592. Here, we demonstrate Toll-like receptor 4 (TLR4) activation can potently induce arrest antiretroviral activity an interferon (IFN)-independent pathway. This pathway requires TLR4 engagement with TRIF, but not involvement TBK1 or IRF3. Exclusive Myd88 activators are unable to trigger dephosphorylation, demonstrating this also Myd88/nuclear factor κB (NF-κB)...
The 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 fully understand how these affect antigenicity Spike, we isolated characterized targeting beyond already identified epitopes. Using recombinant as a sorting bait,...
Evolution of SARS-CoV-2 in long-term persistent infections is hypothesised to be a major source variants concern (VOC). However, the linkage intra-host into haplotypes that reflect viral subpopulations has been limited by commonly used genomic sequencing techniques. We developed and bioinformatic workflow for identifying full-length spike analysed their diversification over course individuals with inherited or acquired immunodeficiencies. Mutations frequently emerged positions found VOCs...
SUMMARY Variants of concern (VOCs) severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) threaten the global response to COVID-19 pandemic. The alpha (B.1.1.7) variant appeared in UK became dominant Europe and North America early 2021. Spike glycoprotein has acquired a number mutations including P681H mutation polybasic cleavage site that been suggested enhance cleavage. Here, we show protein confers level resistance effects interferon-β (IFNβ) lung epithelial cells. This...
Interferons play a critical role in regulating host immune responses to SARS-CoV-2, but the interferon (IFN)-stimulated gene (ISG) effectors that inhibit SARS-CoV-2 are not well characterized. The IFN-inducible short isoform of human nuclear receptor coactivator 7 (NCOA7) inhibits endocytic virus entry, interacts with vacuolar ATPase, and promotes endo-lysosomal vesicle acidification lysosomal protease activity. Here, we used ectopic expression knockout demonstrate NCOA7 infection by as...
The interferon system is part of the innate immune response that inhibits viruses and other pathogens. This emerged approximately 500 million years ago in early vertebrates.
As SARS-CoV-2 variants continue to emerge globally, a major challenge for COVID-19 vaccination is the generation of durable antibody response with cross-neutralizing activity against both current and newly emerging viral variants. Cross-neutralizing concern (B.1.1.7, P.1 B.1.351) has been observed following vaccination, albeit at reduced potency, but whether vaccines based on Spike glycoprotein these will produce superior not fully investigated. Here, we used sera from individuals infected...
ABSTRACT The appearance of new dominant variants concern (VOCs) severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) threatens the global response to COVID-19 pandemic. Of these, alpha variant (also known as B.1.1.7) that appeared initially in UK became much Europe and North America first half 2021. Spike (S) glycoprotein acquired seven mutations two deletions compared ancestral virus, including P681H mutation polybasic cleavage site has been suggested enhance S cleavage. Here,...
The role of myeloid cells in the pathogenesis SARS-CoV-2 is well established, particular as drivers cytokine production and systemic inflammation characteristic severe COVID-19. However, potential for to act bona fide targets productive infection, specifics entry, remain unclear. Using a panel anti-SARS-CoV-2 monoclonal antibodies (mAbs) we performed detailed assessment antibody-mediated infection monocytes/macrophages. mAbs with most consistent mediate were those targeting conserved region...
ABSTRACT 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 (S). presence a polybasic cleavage site in SARS-CoV-2 S 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...
Abstract Interferons play a critical role in regulating host immune responses to SARS-CoV-2, but the interferon (IFN)-stimulated gene (ISG) effectors that inhibit SARS-CoV-2 are not well characterized. The IFN-inducible short isoform of human nuclear receptor coactivator 7 (NCOA7) inhibits endocytic virus entry, interacts with vacuolar ATPase, and promotes endo-lysosomal vesicle acidification lysosomal protease activity. Here, we used ectopic expression knockout demonstrate NCOA7 infection...
Abstract Monocyte-derived macrophages mostly reside in a resting, G0 state, expressing high levels of dephosphorylated, active SAMHD1. We have previously shown that can re-enter the cell cycle without division, into G1-like state. This re-entry is accompanied by phosphorylation dNTP hydrolase/ antiviral restriction factor SAMHD1 at T592 cyclin-dependent kinase CDK1. HIV-1 successfully infects G1 through exploiting this naturally occurring window opportunity where activity de-activated. Here...
ABSTRACT The zinc finger antiviral protein (ZAP) inhibits viral replication by directly binding CpG dinucleotides in cytoplasmic RNA to inhibit synthesis and target the for degradation. ZAP evolved tetrapods there are clear orthologs reptiles, birds mammals. When emerged, other proteins may have become cofactors its activity. KHNYN is a putative endoribonuclease that required restrict retroviruses. To determine evolutionary path after we compared mammals reptiles those fish, which do not...
ABSTRACT The zinc finger antiviral protein (ZAP) restricts a broad range of viruses by binding CpG dinucleotides in viral RNA to target it for degradation and inhibit its translation. KHNYN was recently identified as an required ZAP retroviral replication, though little is known about functional determinants. contains N-terminal extended di-KH-like domain, PIN endoribonuclease domain C-terminal CUBAN that binds NEDD8 ubiquitin. We show deletion the di-KH reduces activity. However, despite...