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The Veterinary Quarterly Dec 2023Influenza A virus is a negative-sense single-stranded RNA virus that belongs to Orthomyxoviridae family. Based on the antigenic characteristics of hemagglutinin (HA) and... (Review)
Review
Influenza A virus is a negative-sense single-stranded RNA virus that belongs to Orthomyxoviridae family. Based on the antigenic characteristics of hemagglutinin (HA) and neuraminidase (NA) influenza viruses are classified into multiple subtypes. H9N2 belongs to the low pathogenic Avian Influenza Viruses (AIVs) and is one of the widely spread viruses in poultry, which can pose a threat to humans by directly infecting or providing internal genes for various zoonotic avian influenza strains. It has the potential to directly or indirectly participate in becoming an AIV that causes a human pandemic. When the virus enters a host, the innate immune system is activated first by pattern recognition receptors. The cytokines produced at the site of infection recruit innate immune cells and antigen-presenting cells and those cells subsequently transmit antigenic signals to adaptive immune cells (i.e. B cells and T cells), to trigger specific humoral and cellular immune responses. As a result, humoral and cellular immunity can clear virus and infected cells antibody-mediated neutralization and cytotoxicity, respectively. Understanding how chicken immune systems respond to H9N2 is a top priority for effectively controlling the virus's spread and designing vaccines. In this review, we comprehensively discuss the role of the chicken immune system in defending against H9N2, and clarify the current limitations in understanding chicken immune responses to H9N2 virus, thereby providing potential directions for future research as research on the chicken respiratory mucosal immune system has been stagnant for more than 20 years especially on how the mucosal immune system in chicken responds to avian influenza.
Topics: Animals; Humans; Chickens; Influenza in Birds; Influenza A Virus, H9N2 Subtype; Poultry; Immune System
PubMed: 37357919
DOI: 10.1080/01652176.2023.2228360 -
Nature Oct 2023Non-segmented negative-strand RNA viruses, including Ebola virus (EBOV), rabies virus, human respiratory syncytial virus and pneumoviruses, can cause respiratory...
Non-segmented negative-strand RNA viruses, including Ebola virus (EBOV), rabies virus, human respiratory syncytial virus and pneumoviruses, can cause respiratory infections, haemorrhagic fever and encephalitis in humans and animals, and are considered a substantial health and economic burden worldwide. Replication and transcription of the viral genome are executed by the large (L) polymerase, which is a promising target for the development of antiviral drugs. Here, using the L polymerase of EBOV as a representative, we show that de novo replication of L polymerase is controlled by the specific 3' leader sequence of the EBOV genome in an enzymatic assay, and that formation of at least three base pairs can effectively drive the elongation process of RNA synthesis independent of the specific RNA sequence. We present the high-resolution structures of the EBOV L-VP35-RNA complex and show that the 3' leader RNA binds in the template entry channel with a distinctive stable bend conformation. Using mutagenesis assays, we confirm that the bend conformation of the RNA is required for the de novo replication activity and reveal the key residues of the L protein that stabilize the RNA conformation. These findings provide a new mechanistic understanding of RNA synthesis for polymerases of non-segmented negative-strand RNA viruses, and reveal important targets for the development of antiviral drugs.
Topics: Animals; Humans; Antiviral Agents; Ebolavirus; Hemorrhagic Fever, Ebola; RNA, Viral; RNA-Dependent RNA Polymerase; Virus Replication; Genome, Viral; Nucleic Acid Conformation; Mutagenesis; RNA Stability
PubMed: 37699521
DOI: 10.1038/s41586-023-06608-1 -
Viruses Aug 2023currently encompasses seven genera and 53 species. Multiple hantaviruses such as Hantaan virus, Seoul virus, Dobrava-Belgrade virus, Puumala virus, Andes virus, and Sin... (Review)
Review
currently encompasses seven genera and 53 species. Multiple hantaviruses such as Hantaan virus, Seoul virus, Dobrava-Belgrade virus, Puumala virus, Andes virus, and Sin Nombre virus are highly pathogenic to humans. They cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome or hantavirus pulmonary syndrome (HCPS/HPS) in many countries. Some hantaviruses infect wild or domestic animals without causing severe symptoms. Rodents, shrews, and bats are reservoirs of various mammalian hantaviruses. Recent years have witnessed significant advancements in the study of hantaviruses including genomics, taxonomy, evolution, replication, transmission, pathogenicity, control, and patient treatment. Additionally, new hantaviruses infecting bats, rodents, shrews, amphibians, and fish have been identified. This review compiles these advancements to aid researchers and the public in better recognizing this zoonotic virus family with global public health significance.
Topics: Animals; Humans; Public Health; Chiroptera; Shrews; RNA Viruses; Orthohantavirus
PubMed: 37632047
DOI: 10.3390/v15081705 -
Archives of Microbiology Dec 2023Many zoonotic disease emergencies are associated with RNA viruses in rodents that substantially impact public health. With the widespread application of meta-genomics... (Review)
Review
Many zoonotic disease emergencies are associated with RNA viruses in rodents that substantially impact public health. With the widespread application of meta-genomics and meta-transcriptomics for virus discovery over the last decade, viral sequences deposited in public databases have expanded rapidly, and the number of novel viruses discovered in rodents has increased. As important reservoirs of zoonotic viruses, rodents have attracted increasing attention for the risk of potential spillover of rodent-borne viruses. However, knowledge of rodent viral diversity and the major factors contributing to the risk of zoonotic epidemic outbreaks remains limited. Therefore, this study analyzes the diversity and composition of rodent RNA viruses using virus records from the Database of Rodent-associated Viruses (DRodVir/ZOVER), which covers the published literatures and records in GenBank database, reviews the main rodent RNA virus-induced human infectious diseases, and discusses potential challenges in this field.
Topics: Animals; Humans; Rodentia; Zoonoses; Viruses; RNA Viruses; Disease Outbreaks
PubMed: 38038743
DOI: 10.1007/s00203-023-03732-4 -
Viruses Nov 2023Interferon-induced transmembrane proteins (IFITM1, 2 and 3) are important host antiviral defense factors. They are active against viruses like the influenza A virus... (Review)
Review
Interferon-induced transmembrane proteins (IFITM1, 2 and 3) are important host antiviral defense factors. They are active against viruses like the influenza A virus (IAV), dengue virus (DENV), Ebola virus (EBOV), Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In this review, we focus on IFITM3 -palmitoylation, a reversible lipid modification, and describe its role in modulating IFITM3 antiviral activity. Our laboratory discovered -palmitoylation of IFITMs using chemical proteomics and demonstrated the importance of highly conserved fatty acid-modified Cys residues in IFITM3 antiviral activity. Further studies showed that site-specific -palmitoylation at Cys72 is important for IFITM3 trafficking to restricted viruses (IAV and EBOV) and membrane-sterol interactions. Thus, site-specific lipid modification of IFITM3 directly regulates its antiviral activity, cellular trafficking, and membrane-lipid interactions.
Topics: Humans; Lipoylation; Zika Virus Infection; RNA-Binding Proteins; Zika Virus; Influenza A virus; Antiviral Agents; Lipids; Membrane Proteins
PubMed: 38140570
DOI: 10.3390/v15122329 -
Journal of Molecular Biology Aug 2023An emerging set of results suggests that liquid-liquid phase separation (LLPS) is the basis for the formation of membrane-less compartments in cells. Evidence is now... (Review)
Review
An emerging set of results suggests that liquid-liquid phase separation (LLPS) is the basis for the formation of membrane-less compartments in cells. Evidence is now mounting that various types of virus-induced membrane-less compartments and organelles are also assembled via LLPS. Specifically, viruses appear to use intracellular phase transitions to form subcellular microenvironments known as viral factories, inclusion bodies, or viroplasms. These compartments - collectively referred to as viral biomolecular condensates - can be used to concentrate replicase proteins, viral genomes, and host proteins that are required for virus replication. They can also be used to subvert or avoid the intracellular immune response. This review examines how certain DNA or RNA viruses drive the formation of viral condensates, the possible biological functions of those condensates, and the biophysical and biochemical basis for their assembly.
Topics: RNA Viruses; Virus Replication; DNA Viruses; Phase Transition; Biomolecular Condensates
PubMed: 36642156
DOI: 10.1016/j.jmb.2023.167955 -
Nature Microbiology Nov 2023Vaccines based on historical virus isolates provide limited protection from continuously evolving RNA viruses, such as influenza viruses or coronaviruses, which... (Review)
Review
Vaccines based on historical virus isolates provide limited protection from continuously evolving RNA viruses, such as influenza viruses or coronaviruses, which occasionally spill over between animals and humans. Despite repeated booster immunizations, population-wide declines in the neutralization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have occurred. This has been compared to seasonal influenza vaccinations in humans, where the breadth of immune responses induced by repeat exposures to antigenically distinct influenza viruses is confounded by pre-existing immunity-a mechanism known as imprinting. Since its emergence, SARS-CoV-2 has evolved in a population with partial immunity, acquired by infection, vaccination or both. Here we critically examine the evidence for and against immune imprinting in host humoral responses to SARS-CoV-2 and its implications for coronavirus disease 2019 (COVID-19) booster vaccine programmes.
Topics: Animals; Humans; COVID-19 Vaccines; SARS-CoV-2; Vaccination; Orthomyxoviridae
PubMed: 37932355
DOI: 10.1038/s41564-023-01505-9 -
Cell Death & Disease Jul 2023Uncontrolled viral replication and excessive inflammation are the main causes of death in the host infected with virus. Hence inhibition of intracellular viral...
Uncontrolled viral replication and excessive inflammation are the main causes of death in the host infected with virus. Hence inhibition of intracellular viral replication and production of innate cytokines, which are the key strategies of hosts to fight virus infections, need to be finely tuned to eliminate viruses while avoid harmful inflammation. The E3 ligases in regulating virus replication and subsequent innate cytokines production remain to be fully characterized. Here we report that the deficiency of the E3 ubiquitin-protein ligase HECTD3 results in accelerated RNA virus clearance and reduced inflammatory response both in vitro and in vivo. Mechanistically, HECTD3 interacts with dsRNA-dependent protein kinase R (PKR) and mediates Lys33-linkage of PKR, which is the first non-proteolytic ubiquitin modification for PKR. This process disrupts the dimerization and phosphorylation of PKR and subsequent EIF2α activation, which results in the acceleration of virus replication, but promotes the formation of PKR-IKK complex and subsequent inflammatory response. The finding suggests HECTD3 is the potential therapeutic target for simultaneously restraining RNA virus replication and virus-induced inflammation once pharmacologically inhibited.
Topics: Humans; Ubiquitin-Protein Ligases; Phosphorylation; Virus Replication; Cytokines; RNA, Double-Stranded; Viruses; Protein Kinases; Inflammation; RNA Viruses; eIF-2 Kinase
PubMed: 37402711
DOI: 10.1038/s41419-023-05923-9 -
Virulence Dec 2023Paramyxoviruses are a family of single-stranded negative-sense RNA viruses, many of which are responsible for a range of respiratory and neurological diseases in humans... (Review)
Review
Paramyxoviruses are a family of single-stranded negative-sense RNA viruses, many of which are responsible for a range of respiratory and neurological diseases in humans and animals. Among the most notable are the henipaviruses, which include the deadly Nipah (NiV) and Hendra (HeV) viruses, the causative agents of outbreaks of severe disease and high case fatality rates in humans and animals. NiV and HeV are maintained in fruit bat reservoirs primarily in the family and spillover into humans directly or by an intermediate amplifying host such as swine or horses. Recently, non-chiropteran associated Langya (LayV), Gamak (GAKV), and Mojiang (MojV) viruses have been discovered with confirmed or suspected ability to cause disease in humans or animals. These viruses are less genetically related to HeV and NiV yet share many features with their better-known counterparts. Recent advances in surveillance of wild animal reservoir viruses have revealed a high number of henipaviral genome sequences distributed across most continents, and mammalian orders previously unknown to harbour henipaviruses. In this review, we summarize the current knowledge on the range of pathogenesis observed for the henipaviruses as well as their replication cycle, epidemiology, genomics, and host responses. We focus on the most pathogenic viruses, including NiV, HeV, LayV, and GAKV, as well as the experimentally non-pathogenic CedV. We also highlight the emerging threats posed by these and potentially other closely related viruses.
Topics: Animals; Humans; Swine; Horses; Virulence; Henipavirus Infections; Nipah Virus; Hendra Virus; Disease Outbreaks; Chiroptera
PubMed: 37948320
DOI: 10.1080/21505594.2023.2273684 -
Microbiology and Molecular Biology... Dec 2023SUMMARYNegative and ambisense RNA viruses are the causative agents of important human diseases such as influenza, measles, Lassa fever, and Ebola hemorrhagic fever. The... (Review)
Review
SUMMARYNegative and ambisense RNA viruses are the causative agents of important human diseases such as influenza, measles, Lassa fever, and Ebola hemorrhagic fever. The viral genome of these RNA viruses consists of one or more single-stranded RNA molecules that are encapsidated by viral nucleocapsid proteins to form a ribonucleoprotein complex (RNP). This RNP acts as protection, as a scaffold for RNA folding, and as the context for viral replication and transcription by a viral RNA polymerase. However, the roles of the viral nucleoproteins extend beyond these functions during the viral infection cycle. Recent advances in structural biology techniques and analysis methods have provided new insights into the formation, function, dynamics, and evolution of negative sense virus nucleocapsid proteins, as well as the role that they play in host innate immune responses against viral infection. In this review, we discuss the various roles of nucleocapsid proteins, both in the context of RNPs and in RNA-free states, as well as the open questions that remain.
Topics: Humans; RNA Viruses; Ribonucleoproteins; RNA, Viral; Virus Replication; Nucleocapsid Proteins; Virus Diseases
PubMed: 37750733
DOI: 10.1128/mmbr.00082-23