Earthusiastic’s Post

”Latent” viruses such as EBV, Cytomegalo and HHV-6 wreaks havoc in our bodies and brains. Add also SARS-CoV-2 to the mix of chronic pathogens that we harbour. Chronic pathogens are the culprit of many, if not most of modern day’s incurable disabling diseases, including MS and Alzheimers. Governments need to implement moonshot funding of virology research in order for effective antiviral treatments and vaccines to develop, the type of medications that will eradicate the source of disease mechanisms that would otherwise lead to some of the most prevalent chronic diseases that big pharma profits on.

Many bacteria utilize quorum sensing (QS) to coordinate group behaviours, and recently, this mechanism has been identified in bacteriophages (phages) as well. Phages can either release their own signalling molecules or eavesdrop on the host's communication system to alternate between lytic and lysogenic modes of infection. In this study, the interaction of Vibrio cholerae with the lysogenic phage VP882 was examined, which is activated by the QS signal DPO. The findings reveal that the activation of VP882 leads to the attachment of phage transcripts to the primary RNA chaperone Hfq, which competes with and reduces the levels of host-produced small RNAs (sRNAs). VP882 also produces sRNAs that bind to Hfq, and one of these sRNAs, known as VpdS, enhances phage replication by managing levels of host and phage mRNA. Additionally, it was demonstrate that host-generated sRNAs can hinder phage replication by diminishing phage mRNA expression, suggesting they may function as part of the host's defense against phages. https://buff.ly/3UzLsIS

Human cytomegalovirus degrades #DMXL1 to inhibit autophagy, lysosomal acidification, and viral assembly :- •Human cytomegalovirus (HCMV) is an important human pathogen that regulates host immunity and hijacks host compartments, including lysosomes, to assemble virions. •We combined a quantitative proteomic analysis of HCMV infection with a database of proteins involved in vacuolar acidification, revealing Dmx-like protein-1 (DMXL1) as the only protein that acidifies vacuoles yet is degraded by HCMV. •Systematic comparison of viral deletion mutants reveals the uncharacterized 7 kDa US33A protein as necessary and sufficient for DMXL1 degradation, which occurs via recruitment of the E3 ubiquitin ligase Kip1 ubiquitination-promoting complex (KPC). •US33A-mediated DMXL1 degradation inhibits lysosome acidification and autophagic cargo degradation. •Formation of the virion assembly compartment, which requires lysosomes, occurs significantly later with US33A-expressing virus infection, with reduced viral replication. •These data thus identify a viral strategy for cellular remodeling, with the potential to employ US33A in therapies for viral infection or rheumatic conditions, in which inhibition of lysosome acidification can attenuate disease. #highlights :- •Systematic proteomic definition of the function of seven HCMV proteins. •HCMV US33A hijacks the KPC E3 ligase and is necessary and sufficient to degrade DMXL1. •DMXL1 degradation inhibits lysosomal acidification and autophagic cargo degradation. •DMXL1 degradation inhibits virion assembly compartment formation and viral release.

https://lnkd.in/gyXC7qyh The lung-cell type that’s most susceptible to infection by SARS-CoV-2, the virus that causes COVID-19, is not the one previously assumed to be most vulnerable. What’s more, the virus enters this susceptible cell via an unexpected route. The medical consequences may be significant. Stanford Medicine investigators have implicated a type of immune cell known as an interstitial macrophage in the critical transition from a merely bothersome COVID-19 case to a potentially deadly one. Interstitial macrophages are situated deep in the lungs, ordinarily protecting that precious organby, among other things, engorging viruses, bacteria, fungi and dust particles that make their way down our airways. But it’s these very cells, the researchers have shown in a study published online April 10 in the Journal of Experimental Medicine, that of all known types of cells composing lung tissue are most susceptible to infection by SARS-CoVid.

This excellent paper by Ikeda et. al. describes studies on higher-order structure of adeno-associated virus serotype 8 by hydrogen/deuterium exchange mass spectrometry. Quoting from the abstract: "The higher-order structure (HOS) is a critical quality attribute of recombinant adeno-associated viruses (rAAVs). Evaluating the HOS of the entire rAAV capsid is challenging because of the flexibility and/or less folded nature of the VP1 unique (VP1u) and VP1/VP2 common regions, which are structural features essential for these regions to exert their functions following viral infection. In this study, hydrogen/deuterium exchange mass spectrometry (HDX-MS) was used for the structural analysis of full and empty rAAV8 capsids. We obtained 486 peptides representing 85% sequence coverage. Surprisingly, the VP1u region showed rapid deuterium uptake even though this region contains the phospholipase A2 domain composed primarily of α-helices. The comparison of deuterium uptake between full and empty capsids showed significant protection from hydrogen/deuterium exchange in the full capsid at the channel structure of the 5-fold symmetry axis. This corresponds to cryo-electron microscopy studies in which the extended densities were observed only in the full capsid. In addition, deuterium uptake was reduced in the VP1u region of the full capsid, suggesting the folding and/or interaction of this region with the encapsidated genome. This study demonstrated HDX-MS as a powerful method for probing the structure of the entire rAAV capsid."

"Many studies have shown that macrophages can internalize viruses and degrade them in lysosomes for clearance in vivo. Inspired by these natural behaviors and using SARS-CoV-2 as a testbed, researchers harvest lysosomes from activated macrophages and anchor the protein-receptor ACE2 as bait, thus constructing a lysosomal “TRAP” (lysoTRAP) that selectively captures, internalizes, and eventually degrades SARS-CoV-2. Through experiments with cells, female mice, female hamsters, and human lung organoids, we demonstrate that lysoTRAP effectively clears SARS-CoV-2." https://lnkd.in/eXybvhWX #lysosomes #virus clearance

📃Scientific paper: Coinfection of Parvovirus B19 with Influenza A/H1N1 Causes Fulminant Myocarditis and Pneumonia. An Autopsy Case Report Abstract: International audience; Parvovirus-B19 (PVB19) is a frequent causative agent of myocarditis. For unclear reasons, viral reactivation can cause acute myocarditis, a leading cause of sudden death in the young. Influenza A/H1N1(2009) virus (IAV/H1N1) is known for causing flu/pneumonia, but the heart is rarely involved. Co-infections of cardiotropic viruses are rarely reported and the mechanisms of viral interactions remain unknown. A 5-year old girl had a flu-like syndrome, when she suddenly presented with a respiratory distress and cardiac arrest. At autopsy, the lungs were found haemorrhagic. Lungs’ histology showed severe bronchiolitis, diffuse haemorrhagic necrosis, and mononuclear inflammation. In the heart, a moderate inflammation was found with no necrosis. IAV/H1N1 was detected in nasal and tracheal swabs, lungs, and the heart. The viral load was high in the lungs, but low in the heart. PVB19 was detected in the heart with a high viral load. Viral coinfection increases the risk of severe outcome but the mechanisms of interaction between viruses are poorly understood. In our case, viral loads suggested a reactivated PVB19-induced acute myocarditis during an IAV/H1N1 pneumonia. Viral interactions may involve an IAV/H1N1-induced cytokine storm, with a fulminant fatal outcome. Clinically, our case shows the importance of investigating inflammatory pathways as therapeutic targets. Continued on ES/IODE ➡️ https://etcse.fr/Y5TGM ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Coinfection of Parvovirus B19 with Influenza A/H1N1 Causes Fulminant Myocarditis and Pneumonia. An Autopsy Case Report Abstract: International audience; Parvovirus-B19 (PVB19) is a frequent causative agent of myocarditis. For unclear reasons, viral reactivation can cause acute myocarditis, a leading cause of sudden death in the young. Influenza A/H1N1(2009) virus (IAV/H1N1) is known for causing flu/pneumonia, but the heart is rarely involved. Co-infections of cardiotropic viruses are rarely reported and the mechanisms of viral interactions remain unknown. A 5-year old girl had a flu-like syndrome, when she suddenly presented with a respiratory distress and cardiac arrest. At autopsy, the lungs were found haemorrhagic. Lungs’ histology showed severe bronchiolitis, diffuse haemorrhagic necrosis, and mononuclear inflammation. In the heart, a moderate inflammation was found with no necrosis. IAV/H1N1 was detected in nasal and tracheal swabs, lungs, and the heart. The viral load was high in the lungs, but low in the heart. PVB19 was detected in the heart with a high viral load. Viral coinfection increases the risk of severe outcome but the mechanisms of interaction between viruses are poorly understood. In our case, viral loads suggested a reactivated PVB19-induced acute myocarditis during an IAV/H1N1 pneumonia. Viral interactions may involve an IAV/H1N1-induced cytokine storm, with a fulminant fatal outcome. Clinically, our case shows the importance of investigating inflammatory pathways as therapeutic targets. Continued on ES/IODE ➡️ https://etcse.fr/Y5TGM ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Innovative Natural Killer Cell Mimic to Combat Intracellular Pathogens Recent research introduces a groundbreaking natural killer (NK) cell mimic designed to target and eliminate intracellular pathogens. By simulating NK cell functions, this approach could enhance the immune response against pathogens hidden within host cells, which traditional therapies often struggle to reach. This promising advance opens new possibilities for treating infections like tuberculosis and certain viral diseases, potentially offering a more precise and effective solution to intracellular infections. #Immunotherapy #InfectiousDiseases #BiomedicalInnovation

WEBINAR: Advances in genomic profiling of respiratory viral pathogens In this webinar, we heard from Dr. Daniel Maloney on whole genome amplification of, and characterisation of Respiratory Syncytial Virus (RSV) A and B. He discussed the group’s results from eight laboratories in five countries, providing insight into the circulating diversity of RSV. By contrast, Dr. Nick Gauthier described an end-to-end, metagenomic next-generation sequencing (mNGS) assay for the pathogen-agnostic detection of respiratory viruses. In this webinar, viewers learnt: 1.). How you can use nanopore technology for viral respiratory pathogen surveillance. 2.). How to perform targeted viral sequencing of Respiratory Syncytial Virus for the purposes of genomic surveillance. 3.). About the potential utility of metagenomic nanopore sequencing for infection control and public health surveillance. https://lnkd.in/gkcNrTd3