A5090139633- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- RNA and protein synthesis mechanisms
- COVID-19 Clinical Research Studies
- Virus-based gene therapy research
- Animal Virus Infections Studies
- Respiratory viral infections research
- Animal Disease Management and Epidemiology
- Viral Infections and Immunology Research
- Optimism, Hope, and Well-being
- Retinal and Optic Conditions
- Click Chemistry and Applications
- Viral gastroenteritis research and epidemiology
- Long-Term Effects of COVID-19
- COVID-19 and healthcare impacts
Imperial College London
2019-2024
The London College
2020
SummaryBackgroundSevere COVID-19 has a high mortality rate. Comprehensive pathological descriptions of are scarce and limited in scope. We aimed to describe the histopathological findings viral tropism patients who died severe COVID-19.MethodsIn this case series, were considered eligible if they older than 18 years, with premortem diagnosis acute respiratory syndrome coronavirus 2 infection listed clinically as direct cause death. Between March 1 April 30, 2020, full post-mortem examinations...
Summary SARS-CoV-2 enters cells via its spike glycoprotein which must be cleaved sequentially at the S1/S2, then S2’ cleavage sites (CS) to mediate membrane fusion. has a unique polybasic insertion S1/S2 CS, we demonstrate can by furin. Using lentiviral pseudotypes and cell-culture adapted virus with deletion, show that is selected for in lung primary human airway epithelial cultures but against Vero E6, cell line used passaging SARS-CoV-2. We find this selective advantage depends on...
Influenza viruses naturally reside in wild aquatic birds. However, the high mutation rate of influenza allows them to rapidly and frequently adapt new hosts, including mammals.
Abstract Avian influenza A viruses (IAVs) pose a public health threat, as they are capable of triggering pandemics by crossing species barriers. Replication avian IAVs in mammalian cells is hindered species-specific variation acidic nuclear phosphoprotein 32 (ANP32) proteins, which essential for viral RNA genome replication. Adaptive mutations enable the IAV polymerase (FluPolA) to surmount this barrier. Here, we present cryo-electron microscopy structures monomeric and dimeric H5N1 FluPolA...
Abstract Human ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most viruses cannot replicate in edited human cells lacking both ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an A these unexpectedly, after 2 passages, observe robust viral We find two mutations different subunits of the polymerase that enable mutant to use a novel factor, ANP32E, alternative family member, which is unable support wild...
Abstract Rationale The secondary thrombotic/vascular clinical syndrome of COVID-19 suggests that SARS-CoV-2 infects not only respiratory epithelium but also the endothelium activating thrombotic pathways, disrupting barrier function and allowing access virus to other organs body. However, a direct test susceptibility authentic endothelial cell lines has been performed. Objective To determine infectibility primary with live pseudoviruses expressing spike protein. Methods Results Expression...
SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness, although extrapulmonary involvement, such in gastrointestinal tract and nervous system, well frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at histological level, however, remains unclear. Here, we perform comprehensive validation monoclonal antibody against nucleocapsid protein (NP) followed by systematic multisystem immunohistochemistry analysis...
To infect humans and cause a pandemic, avian influenza must first adapt to use human versions of the proteins virus hijacks for replication, instead orthologues found in bird cells. One critical host protein is ANP32.
Avian influenza viruses occasionally infect and adapt to mammals, including humans. Swine are often described as "mixing vessels," being susceptible both avian- human-origin viruses, which allows the emergence of novel reassortants, such precursor 2009 H1N1 pandemic. ANP32 proteins host factors that act virus polymerase cofactors. In this study, we describe how swine ANP32A, uniquely among mammalian tested, supports activity avian-origin polymerases avian replication. We further show after...
Abstract Avian influenza viruses occasionally infect and adapt to mammals, including humans. Swine are often described as ‘mixing vessels’, being susceptible both avian human origin viruses, which allows the emergence of novel reassortants, such precursor 2009 H1N1 pandemic. ANP32 proteins host factors that act virus polymerase cofactors. In this study we describe how swine ANP32A, uniquely among mammalian tested, supports some, albeit limited, activity polymerases. We further show after...
Abstract ANP32 proteins, which act as influenza polymerase co-factors, vary between birds and mammals. The well-known mammalian adaptation, PB2-E627K, enables to use proteins. However, some mammalian-adapted viruses do not harbour this adaptation. Here, we show that alternative PB2 adaptations, Q591R D701N also allow PB2-E627K strongly favours of ANP32B whereas shows no such bias. Accordingly, adaptation emerges in species with strong pro-viral humans mice, while is more commonly seen...
Abstract Host restriction limits the emergence of novel pandemic strains from Influenza A Virus avian reservoir. For efficient replication in mammalian cells, influenza RNA-dependent RNA polymerase must adapt to use human orthologues host factor ANP32, which lack a 33 amino acid insertion relative ANP32A. Here we find that requires ANP32 proteins support both steps replication: cRNA and vRNA synthesis. Nevertheless, are only restricted synthesis cells. Therefore, can synthesis, without...
<title>Abstract</title> Avian influenza A viruses (IAVs) pose a public health threat, as they are capable of triggering pandemics by crossing species barriers. Replication avian IAVs in mammalian cells is hindered species-specific variation acidic nuclear phosphoprotein 32 (ANP32) proteins, which essential for viral RNA genome replication. Adaptive mutations enable the IAV polymerase (FluPolA) to surmount this barrier. Here, we present cryo-electron microscopy structures monomeric and...
Influenza A viruses (IAVs) have a significant impact on public health through seasonal epidemics. Moreover, the sporadic emergence of zoonotic and pandemic strains represents an additional global threat. Understanding how novel IAV adapt to infect transmit between humans is essential for effective surveillance may provide rationale anti-viral therapeutics. IAVs replicate their RNA genomes in host cell nucleus. Host proteins, such as proviral factor ANP32, are co-opted support viral...