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Viruses Mar 2021Human metapneumovirus (hMPV) is one of the main pathogens responsible for acute respiratory infections in children up to 5 years of age, contributing substantially to... (Review)
Review
Human metapneumovirus (hMPV) is one of the main pathogens responsible for acute respiratory infections in children up to 5 years of age, contributing substantially to health burden. The worldwide economic and social impact of this virus is significant and must be addressed. The structural components of hMPV (either proteins or genetic material) can be detected by several receptors expressed by host cells through the engagement of pattern recognition receptors. The recognition of the structural components of hMPV can promote the signaling of the immune response to clear the infection, leading to the activation of several pathways, such as those related to the interferon response. Even so, several intrinsic factors are capable of modulating the immune response or directly inhibiting the replication of hMPV. This article will discuss the current knowledge regarding the innate and adaptive immune response during hMPV infections. Accordingly, the host intrinsic components capable of modulating the immune response and the elements capable of restricting viral replication during hMPV infections will be examined.
Topics: Adaptive Immunity; Child, Preschool; Host Microbial Interactions; Humans; Immunity, Innate; Metapneumovirus; Paramyxoviridae Infections
PubMed: 33809875
DOI: 10.3390/v13030519 -
Viruses Oct 2023Henipaviruses are single-stranded RNA viruses that have been shown to be virulent in several species, including humans, pigs, horses, and rodents. Isolated nearly 30... (Review)
Review
Henipaviruses are single-stranded RNA viruses that have been shown to be virulent in several species, including humans, pigs, horses, and rodents. Isolated nearly 30 years ago, these viruses have been shown to be of particular concern to public health, as at least two members (Nipah and Hendra viruses) are highly virulent, as well as zoonotic, and are thus classified as BSL4 pathogens. Although only 5 members of this genus have been isolated and characterized, metagenomics analysis using animal fluids and tissues has demonstrated the existence of other novel henipaviruses, suggesting a far greater degree of phylogenetic diversity than is currently known. Using a variety of molecular biology techniques, it has been shown that these viruses exhibit varying degrees of tropism on a species, organ/tissue, and cellular level. This review will attempt to provide a general overview of our current understanding of henipaviruses, with a particular emphasis on viral tropism.
Topics: Humans; Animals; Horses; Swine; Henipavirus Infections; Phylogeny; Hendra Virus; Viral Tropism; Tropism; Nipah Virus
PubMed: 37896825
DOI: 10.3390/v15102048 -
MBio Feb 2022Canine distemper virus (CDV) is a highly contagious pathogen and is known to enter the host via the respiratory tract and disseminate to various organs. Current...
Canine distemper virus (CDV) is a highly contagious pathogen and is known to enter the host via the respiratory tract and disseminate to various organs. Current hypotheses speculate that CDV uses the homologous cellular receptors of measles virus (MeV), SLAM and nectin-4, to initiate the infection process. For validation, here, we established the well-differentiated air-liquid interface (ALI) culture model from primary canine tracheal airway epithelial cells. By applying the green fluorescent protein (GFP)-expressing CDV vaccine strain and recombinant wild-type viruses, we show that cell-free virus infects the airway epithelium mainly via the paracellular route and only after prior disruption of tight junctions by pretreatment with EGTA; this infection was related to nectin-4 but not to SLAM. Remarkably, when CDV-preinfected DH82 cells were cocultured on the basolateral side of canine ALI cultures grown on filter supports with a 1.0-μm pore size, cell-associated CDV could be transmitted via cell-to-cell contact from immunocytes to airway epithelial cultures. Finally, we observed that canine ALI cultures formed syncytia and started to release cell-free infectious viral particles from the apical surface following treatment with an inhibitor of the JAK/STAT signaling pathway (ruxolitinib). Our findings show that CDV can overcome the epithelial barrier through different strategies, including infection via immunocyte-mediated transmission and direct infection via the paracellular route when tight junctions are disrupted. Our established model can be adapted to other animals for studying the transmission routes and the pathogenicity of other morbilliviruses. Canine distemper virus (CDV) is not only an important pathogen of carnivores, but it also serves as a model virus for analyzing measles virus pathogenesis. To get a better picture of the different stages of infection, we used air-liquid interface cultures to analyze the infection of well-differentiated airway epithelial cells by CDV. Applying a coculture approach with DH82 cells, we demonstrated that cell-mediated infection from the basolateral side of well-differentiated epithelial cells is more efficient than infection via cell-free virus. In fact, free virus was unable to infect intact polarized cells. When tight junctions were interrupted by treatment with EGTA, cells became susceptible to infection, with nectin-4 serving as a receptor. Another interesting feature of CDV infection is that infection of well-differentiated airway epithelial cells does not result in virus egress. Cell-free virions are released from the cells only in the presence of an inhibitor of the JAK/STAT signaling pathway. Our results provide new insights into how CDV can overcome the barrier of the airway epithelium and reveal similarities and some dissimilarities compared to measles virus.
Topics: Animals; Dogs; Distemper Virus, Canine; Nectins; Egtazic Acid; Receptors, Cell Surface; Measles virus; Cell Adhesion Molecules; Respiratory Mucosa; Distemper
PubMed: 35038920
DOI: 10.1128/mbio.03043-21 -
Viruses Sep 2022The viral genus includes two highly virulent zoonotic viruses of serious public health concern. and outbreaks are restricted to Australia and Southeast Asia,...
The viral genus includes two highly virulent zoonotic viruses of serious public health concern. and outbreaks are restricted to Australia and Southeast Asia, respectively. The Henipavirus genus comprises mostly bat-borne viruses, but exceptions have already been described as novel viruses with rodents and shrews as reservoir animals. In the Americas, scarce evidence supports the circulation of these viruses. In this communication, we report a novel henipa-like virus from opossums () from a forest fragment area in the Peixe-Boi municipality, Brazil, after which the virus was named the Peixe-Boi virus (PBV). The application of next-generation sequencing and metagenomic approach led us to discover the original evidence of a henipa-like virus genome in Brazil and South America and the original description of a henipa-like virus in marsupial species. These findings emphasize the importance of further studies to characterize PBV and clarify its ecology, impact on public health, and its relationship with didelphid marsupials and henipaviruses.
Topics: Animals; Henipavirus Infections; Brazil; Hendra Virus; Nipah Virus; Genomics; Chiroptera
PubMed: 36298723
DOI: 10.3390/v14102167 -
Viral Immunology 2021The resolution revolution of cryo-electron microscopy (cryo-EM) has made a significant impact on the structural analysis of the multifunctional RNA polymerases. In...
The resolution revolution of cryo-electron microscopy (cryo-EM) has made a significant impact on the structural analysis of the multifunctional RNA polymerases. In recent months, several high-resolution structures of RNA polymerases of , which includes the human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), have been determined by single-particle cryo-EM. These structures illustrated high similarities and minor differences between the polymerases and revealed the potential mechanisms of the RNA synthesis.
Topics: Cryoelectron Microscopy; DNA-Directed RNA Polymerases; Humans; Pneumovirus; Respiratory Syncytial Virus, Human
PubMed: 32429800
DOI: 10.1089/vim.2020.0018 -
Journal of Virology Jan 2022Human parainfluenza virus 3 (HPIV3) belongs to the Paramyxoviridae, causing annual worldwide epidemics of respiratory diseases, especially in newborns and infants. The...
Human parainfluenza virus 3 (HPIV3) belongs to the Paramyxoviridae, causing annual worldwide epidemics of respiratory diseases, especially in newborns and infants. The core components consist of just three viral proteins: nucleoprotein (N), phosphoprotein (P), and RNA polymerase (L), playing essential roles in replication and transcription of HPIV3 as well as other paramyxoviruses. Viral genome encapsidated by N is as a template and recognized by RNA-dependent RNA polymerase complex composed of L and P. The offspring RNA also needs to assemble with N to form nucleocapsids. The N is one of the most abundant viral proteins in infected cells and chaperoned in the RNA-free form (N) by P before encapsidation. In this study, we presented the structure of unassembled HPIV3 N in complex with the N-terminal portion of the P, revealing the molecular details of the N and the conserved N-P interaction. Combined with biological experiments, we showed that the P binds to the C-terminal domain of N mainly by hydrophobic interaction and maintains the unassembled conformation of N by interfering with the formation of N-RNA oligomers, which might be a target for drug development. Based on the complex structure, we developed a method to obtain the monomeric N. Furthermore, we designed a P-derived fusion peptide with 10-fold higher affinity, which hijacked the N and interfered with the binding of the N to RNA significantly. Finally, we proposed a model of conformational transition of N from the unassembled state to the assembled state, which helped to further understand viral replication. Human parainfluenza virus 3 (HPIV3) causes annual epidemics of respiratory diseases, especially in newborns and infants. For the replication of HPIV3 and other paramyxoviruses, only three viral proteins are required: phosphoprotein (P), RNA polymerase (L), and nucleoprotein (N). Here, we report the crystal structure of the complex of N and its chaperone P. We describe in detail how P acts as a chaperone to maintain the unassembled conformation of N. Our analysis indicated that the interaction between P and N is conserved and mediated by hydrophobicity, which can be used as a target for drug development. We obtained a high-affinity P-derived peptide inhibitor, specifically targeted N, and greatly interfered with the binding of the N to RNA, thereby inhibiting viral encapsidation and replication. In summary, our results provide new insights into the paramyxovirus genome replication and nucleocapsid assembly and lay the basis for drug development.
Topics: Amino Acid Sequence; Antiviral Agents; Crystallography, X-Ray; Hydrophobic and Hydrophilic Interactions; Molecular Chaperones; Mutation; Nucleocapsid Proteins; Parainfluenza Virus 3, Human; Phosphoproteins; Protein Binding; Protein Conformation; RNA, Viral
PubMed: 34730394
DOI: 10.1128/JVI.01648-21 -
Frontiers in Immunology 2023Human metapneumovirus (HMPV) is a pneumovirus that may cause severe respiratory disease in humans. HMPV infection has been found to increase susceptibility to bacterial...
Human metapneumovirus (HMPV) is a pneumovirus that may cause severe respiratory disease in humans. HMPV infection has been found to increase susceptibility to bacterial superinfections leading to increased morbidity and mortality. The molecular mechanisms underlying HMPV-mediated increase in bacterial susceptibility are poorly understood and largely understudied. Type I interferons (IFNs), while critical for antiviral defenses, may often have detrimental effects by skewing the host immune response and cytokine output of immune cells. It is currently unknown if HMPV skews the inflammatory response in human macrophages triggered by bacterial stimuli. Here we report that HMPV pre-infection impacts production of specific cytokines. HMPV strongly suppresses IL-1β transcription in response to LPS or heat-killed and , while enhancing mRNA levels of IL-6, TNF-α and IFN-β. We demonstrate that in human macrophages the HMPV-mediated suppression of IL-1β transcription requires TANK-binding kinase 1 (TBK1) and signaling via the IFN-β-IFNAR axis. Interestingly, our results show that HMPV pre-infection did not impair the LPS-stimulated activation of NF-κB and HIF-1α, transcription factors that stimulate IL-1β mRNA synthesis in human cells. Furthermore, we determined that sequential HMPV-LPS treatment resulted in accumulation of the repressive epigenetic mark H3K27me3 at the promoter. Thus, for the first time we present data revealing the molecular mechanisms by which HMPV shapes the cytokine output of human macrophages exposed to bacterial pathogens/LPS, which appears to be dependent on epigenetic reprogramming at the promoter leading to reduced synthesis of IL-1β. These results may improve current understanding of the role of type I IFNs in respiratory disease mediated not only by HMPV, but also by other respiratory viruses that are associated with superinfections.
Topics: Humans; Cytokines; Metapneumovirus; Superinfection; Transcription, Genetic; Interleukin-1beta; Interferon-beta; Bacterial Infections; Paramyxoviridae Infections
PubMed: 37435074
DOI: 10.3389/fimmu.2023.1173605 -
Proceedings. Biological Sciences Oct 2021Canine distemper virus (CDV) and phocine distemper virus (PDV) are major pathogens to terrestrial and marine mammals. Yet little is known about the timing and...
Canine distemper virus (CDV) and phocine distemper virus (PDV) are major pathogens to terrestrial and marine mammals. Yet little is known about the timing and geographical origin of distemper viruses and to what extent it was influenced by environmental change and human activities. To address this, we (i) performed the first comprehensive time-calibrated phylogenetic analysis of the two distemper viruses, (ii) mapped distemper antibody and virus detection data from marine mammals collected between 1972 and 2018, and (iii) compiled historical reports on distemper dating back to the eighteenth century. We find that CDV and PDV diverged in the early seventeenth century. Modern CDV strains last shared a common ancestor in the nineteenth century with a marked radiation during the 1930s-1950s. Modern PDV strains are of more recent origin, diverging in the 1970s-1980s. Based on the compiled information on distemper distribution, the diverse host range of CDV and basal phylogenetic placement of terrestrial morbilliviruses, we hypothesize a terrestrial CDV-like ancestor giving rise to PDV in the North Atlantic. Moreover, given the estimated timing of distemper origin and radiation, we hypothesize a prominent role of environmental change such as the Little Ice Age, and human activities like globalization and war in distemper virus evolution.
Topics: Animals; Cetacea; Distemper; Distemper Virus, Canine; Distemper Virus, Phocine; Dogs; Phylogeny
PubMed: 34702073
DOI: 10.1098/rspb.2021.1969 -
Current Opinion in Virology Apr 2020Recently, a lateral flow rapid diagnostic test (RDT) with good accuracy has been described. This test enables measles specific IgM antibody detection in serum, capillary... (Review)
Review
Recently, a lateral flow rapid diagnostic test (RDT) with good accuracy has been described. This test enables measles specific IgM antibody detection in serum, capillary blood and oral fluid. RDTs have the potential to transform measles surveillance by allowing real-time case confirmation outside of central/regional laboratories and by facilitating a timely public health response. Measles virus genes can also be amplified and sequenced consistently from dried IgM-positive RDTs stored outside of cold chain, which will enable more complete virologic surveillance. Critical questions remain regarding operational use of RDTs as part of global measles surveillance. Projects to evaluate RDT use as part of national surveillance programs and to commercialize the RDT are underway.
Topics: Diagnostic Tests, Routine; Epidemiological Monitoring; Global Health; Humans; Measles; Measles virus
PubMed: 32615510
DOI: 10.1016/j.coviro.2020.05.007 -
Potential for Person-to-Person Transmission of Henipaviruses: A Systematic Review of the Literature.The Journal of Infectious Diseases Mar 2024Nipah virus Bangladesh (NiVB) is a bat-borne zoonosis transmitted between people through the respiratory route. The risk posed by related henipaviruses, including Hendra...
Nipah virus Bangladesh (NiVB) is a bat-borne zoonosis transmitted between people through the respiratory route. The risk posed by related henipaviruses, including Hendra virus (HeV) and Nipah virus Malaysia (NiVM), is less clear. We conducted a broad search of the literature encompassing both human infections and animal models to synthesize evidence about potential for person-to-person spread. More than 600 human infections have been reported in the literature, but information on viral shedding was only available for 40 case-patients. There is substantial evidence demonstrating person-to-person transmission of NiVB, and some evidence for NiVM. Less direct evidence is available about the risk for person-to-person transmission of HeV, but animals infected with HeV shed more virus in the respiratory tract than those infected with NiVM, suggesting potential for transmission. As the group of known henipaviruses continues to grow, shared protocols for conducting and reporting from human investigations and animal experiments are urgently needed.
Topics: Animals; Humans; Hendra Virus; Henipavirus Infections; Malaysia; Nipah Virus; Zoonoses
PubMed: 37925626
DOI: 10.1093/infdis/jiad467