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Pediatric Annals Mar 2024
Topics: Humans; Immunization; Vaccination; Respiratory Syncytial Virus, Human
PubMed: 38466331
DOI: 10.3928/19382359-20240214-01 -
International Journal of Biological... Sep 2023As an important structural protein in virion morphogenesis, the matrix (M) protein of Newcastle disease virus (NDV) is demonstrated to be a nuclear-cytoplasmic... (Review)
Review
As an important structural protein in virion morphogenesis, the matrix (M) protein of Newcastle disease virus (NDV) is demonstrated to be a nuclear-cytoplasmic trafficking protein and plays essential roles in viral assembly and budding. In recent years, increasing lines of evidence have indicated that the M protein has obvious influence on the pathotypes of NDV, and the interaction of M protein with cellular proteins is also closely associated with the replication and pathogenicity of NDV. Although substantial progress has been made in the past 40 years towards understanding the structure and function of NDV M protein, the available information is scattered. Therefore, this review article summarizes and updates the research progress on the structural feature, virulence and pathotype correlation, and nucleocytoplasmic transport mechanism of NDV M protein, as well as the functions of M protein and cellular protein interactions in M's intracellular localization, viral RNA synthesis and transcription, viral protein synthesis, viral immune evasion, and viral budding and release, which will provide an in-depth understanding of the biological functions of M protein in the replication and pathogenesis of NDV, and also contribute to the development of effective antiviral strategies aiming at blocking the early or late steps of NDV lifecycles.
Topics: Animals; Humans; Newcastle disease virus; Newcastle Disease; Virus Replication; Chickens; Virus Assembly
PubMed: 37532184
DOI: 10.1016/j.ijbiomac.2023.126089 -
The Lancet. Microbe Dec 2023
Topics: Humans; Henipavirus; Henipavirus Infections; Nervous System Physiological Phenomena
PubMed: 37804851
DOI: 10.1016/S2666-5247(23)00295-1 -
Cellular and Molecular Life Sciences :... Feb 2024The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed... (Review)
Review
The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed that it may also engender severe complications in the context of viral respiratory disease. Here, we review the mechanisms of complement activation and regulation and explore their roles in both protecting against infection and exacerbating disease. We discuss emerging evidence related to complement-targeted therapeutics in COVID-19 and compare the role of the complement in other respiratory viral diseases like influenza and respiratory syncytial virus. We review recent mechanistic studies and animal models that can be used for further investigation. Novel knockout studies are proposed to better understand the nuances of the activation of the complement system in respiratory viral diseases.
Topics: Animals; Humans; COVID-19; Pandemics; Complement System Proteins; Influenza, Human; Respiratory Syncytial Virus, Human
PubMed: 38368584
DOI: 10.1007/s00018-024-05157-8 -
The Lancet. Microbe Mar 2024
Topics: Animals; Humans; Nipah Virus; Public Health; Zoonoses; Henipavirus Infections
PubMed: 38141635
DOI: 10.1016/S2666-5247(23)00361-0 -
Methods in Molecular Biology (Clifton,... 2024Ebola (EBOV) and Marburg (MARV) viruses cause hemorrhagic fever disease in humans and non-human primates (NHPs) with case-fatality rates as high as 90%. The 2013-2016...
Ebola (EBOV) and Marburg (MARV) viruses cause hemorrhagic fever disease in humans and non-human primates (NHPs) with case-fatality rates as high as 90%. The 2013-2016 Ebola virus disease (EVD) outbreak led to over 28,000 cases and 11,000 deaths and took an enormous toll on the economy of West African nations, in the absence of any vaccine or therapeutic options. Like EVD, there have been at least 6 outbreaks of MVD with ~88% case-fatality and the most recent cases emerging in Equatorial Guinea in February 2023. These outbreaks have spurred an unprecedented global effort to develop vaccines and therapeutics for EVD and MVD and led to an approved vaccine (ERVEBO™) and two monoclonal antibody (mAb) therapeutics for EBOV. In contrast to EVD, therapeutic options against Marburg and another Ebola-relative Sudan virus (SUDV) are lacking. The filovirus glycoprotein (GP), which mediates host cell entry and fusion, is the primary target of neutralizing antibodies. In addition to its pre- and post-fusion trimeric states, the protein is highly glycosylated making production of pure and homogeneous trimers on a large scale, a requirement for subunit vaccine development, a challenge. In efforts to address this roadblock, we have developed a unique combination of structure-based design, selection of expression system, and purification methods to produce uniform and stable EBOV and MARV GP trimers at scales appropriate for vaccine production.
Topics: Animals; Humans; Hemorrhagic Fever, Ebola; Antibodies, Viral; Ebolavirus; Marburgvirus; Glycoproteins; Vaccines
PubMed: 38315357
DOI: 10.1007/978-1-0716-3666-4_2 -
Emerging Microbes & Infections Dec 2023Viral RNA synthesis of several non-segmented, negative-sense RNA viruses (NNSVs) takes place in inclusion bodies (IBs) that show properties of liquid organelles, which...
Viral RNA synthesis of several non-segmented, negative-sense RNA viruses (NNSVs) takes place in inclusion bodies (IBs) that show properties of liquid organelles, which are formed by liquid-liquid phase separation of scaffold proteins. It is believed that this is driven by intrinsically disordered regions (IDRs) and/or multiple copies of interaction domains, which for NNSVs are usually located in their nucleo - and phosphoproteins. In contrast to other NNSVs, the Ebola virus (EBOV) nucleoprotein NP alone is sufficient to form IBs without the need for a phosphoprotein, and to facilitate the recruitment of other viral proteins into these structures. While it has been proposed that also EBOV IBs are liquid organelles, this has so far not been formally demonstrated. Here we used a combination of live cell microscopy, fluorescence recovery after photobleaching assays, and mutagenesis approaches together with reverse genetics-based generation of recombinant viruses to study the formation of EBOV IBs. Our results demonstrate that EBOV IBs are indeed liquid organelles, and that oligomerization but not IDRs of the EBOV nucleoprotein plays a key role in their formation. Additionally, VP35 (often considered the phosphoprotein-equivalent of EBOV) is not essential for IB formation, but alters their liquid behaviour. These findings define the molecular mechanism for the formation of EBOV IBs, which play a central role in the life cycle of this deadly virus.
Topics: Humans; Ebolavirus; Hemorrhagic Fever, Ebola; Inclusion Bodies; Nucleoproteins; Phosphoproteins
PubMed: 37306660
DOI: 10.1080/22221751.2023.2223727 -
The Lancet. Microbe Aug 2023
Topics: Humans; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 37390835
DOI: 10.1016/S2666-5247(23)00195-7 -
Communications Biology Oct 2023The respiratory syncytial virus polymerase complex, consisting of the polymerase (L) and phosphoprotein (P), catalyzes nucleotide polymerization, cap addition, and cap...
The respiratory syncytial virus polymerase complex, consisting of the polymerase (L) and phosphoprotein (P), catalyzes nucleotide polymerization, cap addition, and cap methylation via the RNA dependent RNA polymerase, capping, and Methyltransferase domains on L. Several nucleoside and non-nucleoside inhibitors have been reported to inhibit this polymerase complex, but the structural details of the exact inhibitor-polymerase interactions have been lacking. Here, we report a non-nucleoside inhibitor JNJ-8003 with sub-nanomolar inhibition potency in both antiviral and polymerase assays. Our 2.9 Å resolution cryo-EM structure revealed that JNJ-8003 binds to an induced-fit pocket on the capping domain, with multiple interactions consistent with its tight binding and resistance mutation profile. The minigenome and gel-based de novo RNA synthesis and primer extension assays demonstrated that JNJ-8003 inhibited nucleotide polymerization at the early stages of RNA transcription and replication. Our results support that JNJ-8003 binding modulates a functional interplay between the capping and RdRp domains, and this molecular insight could accelerate the design of broad-spectrum antiviral drugs.
Topics: Respiratory Syncytial Virus, Human; RNA-Dependent RNA Polymerase; Protein Binding; RNA; Nucleotides
PubMed: 37865687
DOI: 10.1038/s42003-023-05451-4 -
Frontiers in Immunology 2023Respiratory syncytial virus (RSV) is a significant causative agent of bronchitis and pneumonia in infants and children. The identification and structural analysis of the... (Review)
Review
Respiratory syncytial virus (RSV) is a significant causative agent of bronchitis and pneumonia in infants and children. The identification and structural analysis of the surface fusion glycoprotein of RSV represents a pivotal advancement in the development of RSV prevention. This review provides a comprehensive summary of RSV monoclonal antibody (mAb) and vaccine clinical trials registered on ClinicalTrials.gov, emphasizing on the classification, name, target, phase, clinical outcomes, and safety data of RSV vaccination in newborns, infants and children. We also discuss the characteristics of the types of RSV vaccines for maternal immunity and summarize the current clinical research progress of RSV vaccination in pregnant women and their protective efficacy in infants. This review will provide new ideas for the development of RSV prevention for children in the future.
Topics: Humans; Infant, Newborn; Infant; Child; Female; Pregnancy; Pregnant Women; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Vaccines; Vaccination; Antibodies, Viral
PubMed: 38327765
DOI: 10.3389/fimmu.2023.1329426