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Scientific Reports Jul 2023Lloviu cuevavirus (LLOV) was the first identified member of Filoviridae family outside the Ebola and Marburgvirus genera. A massive die-off of Schreibers's bats...
Lloviu cuevavirus (LLOV) was the first identified member of Filoviridae family outside the Ebola and Marburgvirus genera. A massive die-off of Schreibers's bats (Miniopterus schreibersii) in the Iberian Peninsula in 2002 led to its initial discovery. Recent studies with recombinant and wild-type LLOV isolates confirmed the zoonotic nature of the virus in vitro. We examined bat samples from Italy for the presence of LLOV in an area outside of the currently known distribution range of the virus. We detected one positive sample from 2020, sequenced the complete coding region of the viral genome and established an infectious isolate of the virus. In addition, we performed the first comprehensive evolutionary analysis of the virus, using the Spanish, Hungarian and the Italian sequences. The most important achievement of this study is the establishment of an additional infectious LLOV isolate from a bat sample using the SuBK12-08 cells, demonstrating that this cell line is highly susceptible to LLOV infection and confirming the previous observation that these bats are effective hosts of the virus in nature. This result further strengthens the role of bats as the natural hosts for zoonotic filoviruses.
Topics: Animals; Chiroptera; Filoviridae; Marburgvirus; Cell Line; Italy; Phylogeny
PubMed: 37443182
DOI: 10.1038/s41598-023-38364-7 -
FEBS Letters Sep 2015In this review I summarize available data pointing to the abundance of structural disorder within the nucleoprotein (N) from three paramyxoviruses, namely the measles... (Review)
Review
In this review I summarize available data pointing to the abundance of structural disorder within the nucleoprotein (N) from three paramyxoviruses, namely the measles (MeV), Nipah (NiV) and Hendra (HeV) viruses. I provide a detailed description of the molecular mechanisms that govern the disorder-to-order transition that the intrinsically disordered C-terminal domain (NTAIL) of their N proteins undergoes upon binding to the C-terminal X domain (XD) of the homologous phosphoproteins. I also show that a significant flexibility persists within NTAIL-XD complexes, which makes them illustrative examples of "fuzziness". Finally, I discuss the functional implications of structural disorder for viral transcription and replication in light of the promiscuity of disordered regions and of the considerable reach they confer to the components of the replicative machinery.
Topics: Hendra Virus; Intrinsically Disordered Proteins; Measles virus; Models, Molecular; Nipah Virus; Nucleocapsid Proteins; Pliability; Protein Binding; Protein Folding; Protein Structure, Tertiary
PubMed: 26071376
DOI: 10.1016/j.febslet.2015.05.055 -
Virology May 2015Ebola viruses and Marburg viruses, members of the filovirus family, cause severe hemorrhagic fever. The ability of these viruses to potently counteract host innate... (Review)
Review
Ebola viruses and Marburg viruses, members of the filovirus family, cause severe hemorrhagic fever. The ability of these viruses to potently counteract host innate immune responses is thought to be an important component of viral pathogenesis. Several mechanisms of filoviral innate immune evasion have been defined and are reviewed here. These mechanisms include suppression of type I interferon (IFN) production; inhibition of IFN-signaling and mechanisms that either prevent cell stress responses or allow the virus to replicate in the face of such responses. A greater understanding of these innate immune evasion mechanisms may suggest novel therapeutic approaches for these deadly pathogens.
Topics: Ebolavirus; Host-Pathogen Interactions; Humans; Immune Evasion; Interferon Type I; Marburgvirus; Virus Replication
PubMed: 25843618
DOI: 10.1016/j.virol.2015.03.030 -
Proceedings of the National Academy of... Apr 2024Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and...
Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and fusion (F) glycoproteins which are the main targets of neutralizing antibodies. We show here that the LayV F and G glycoproteins promote membrane fusion with human, mouse, and hamster target cells using a different, yet unknown, receptor than Nipah virus (NiV) and Hendra virus (HeV) and that NiV- and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryoelectron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing their conformational landscape and distinct antigenicity relative to NiV and HeV. We computationally designed stabilized LayV G constructs and demonstrate the generalizability of an HNV F prefusion-stabilization strategy. Our data will support the development of vaccines and therapeutics against LayV and closely related HNVs.
Topics: Humans; Animals; Mice; Cryoelectron Microscopy; Nipah Virus; Hendra Virus; Glycoproteins; Henipavirus Infections; Virus Internalization; Henipavirus
PubMed: 38593070
DOI: 10.1073/pnas.2314990121 -
International Journal of Molecular... Jan 2018Bat rabies cases in Europe are mainly attributed to two lyssaviruses, namely European Bat Lyssavirus 1 (EBLV-1) and European Bat Lyssavirus 2 (EBLV-2). Prior to the... (Review)
Review
Bat rabies cases in Europe are mainly attributed to two lyssaviruses, namely European Bat Lyssavirus 1 (EBLV-1) and European Bat Lyssavirus 2 (EBLV-2). Prior to the death of a bat worker in Finland in 1985, very few bat rabies cases were reported. Enhanced surveillance in the two subsequent years (1986-1987) identified 263 cases (more than a fifth of all reported cases to date). Between 1977 and 2016, 1183 cases of bat rabies were reported, with the vast majority (>97%) being attributed to EBLV-1. In contrast, there have been only 39 suspected cases of EBLV-2, of which 34 have been confirmed by virus typing and presently restricted to just two bat species; and . The limited number of EBLV-2 cases in Europe prompted the establishment of a network of European reference laboratories to collate all available viruses and data. Despite the relatively low number of EBLV-2 cases, a large amount of anomalous data has been published in the scientific literature, which we have here reviewed and clarified. In this review, 29 EBLV-2 full genome sequences have been analysed to further our understanding of the diversity and molecular evolution of EBLV-2 in Europe. Analysis of the 29 complete EBLV-2 genome sequences clearly corroborated geographical relationships with all EBLV-2 sequences clustering at the country level irrespective of the gene studied. Further geographical clustering was also observed at a local level. There are high levels of homogeneity within the EBLV-2 species with nucleotide identities ranging from 95.5-100% and amino acid identities between 98.7% and 100%, despite the widespread distribution of the isolates both geographically and chronologically. The mean substitution rate for EBLV-2 across the five concatenated genes was 1.65 × 10, and evolutionary clock analysis confirms the slow evolution of EBLV-2 both between and within countries in Europe. This is further supported by the first detailed EBLV-2 intra-roost genomic analysis whereby a relatively high sequence homogeneity was found across the genomes of three EBLV-2 isolates obtained several years apart (2007, 2008, and 2014) from at the same site (Stokesay Castle, Shropshire, UK).
Topics: Animals; Evolution, Molecular; Genome, Viral; Humans; Lyssavirus; Philology; Rhabdoviridae Infections
PubMed: 29303971
DOI: 10.3390/ijms19010156 -
Journal of the Neurological Sciences May 2021Several Lyssaviruses are known to be a causative agent of rabies and rabies like syndrome. There are no proven effective treatment strategies for symptomatic rabies...
Several Lyssaviruses are known to be a causative agent of rabies and rabies like syndrome. There are no proven effective treatment strategies for symptomatic rabies patient. Risk of infection from dog variant of rabies virus is highest with deep bite reaching muscular layer and much higher when compared to scratch. Failure of viral eradication at the central nervous system (CNS) is partly due to inadequate immune response. Favipiravir selectively inhibit viral RNA polymerase and has been shown to reduce rabies replication in neuronal cell and mouse model system. Endocannabinoid system has emerged as an important regulator for CNS integrity, cell fate and may serve as an important novel neuroprotective agent. Cannabinoid may be able to regulate the impaired homeostasis induced by rabies virus by promoting infected cell survival and promote complete autophagy in infected cell.
Topics: Animals; Case Management; Central Nervous System; Dogs; Humans; Lyssavirus; Mice; Rabies; Rabies virus
PubMed: 33812240
DOI: 10.1016/j.jns.2021.117413 -
Viruses Aug 2016Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus... (Review)
Review
Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus (RABV) evades the immune response and kills its host. This review investigates the complex interplay between RABV and the immune system, including the various means by which RABV evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. Different factors that influence immune responses-including age, sex, cerebral lateralization and temperature-are discussed, with specific reference to RABV and the effects on host morbidity and mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial mechanism of the host's response to infection. The various RABV proteins and their roles in immune evasion are examined in depth with reference to important domains and the downstream effects of these interactions. Lastly, an overview of the means by which RABV evades important immune responses is provided. The research discussed in this review will be important in determining the roles of the immune response during RABV infections as well as to highlight important therapeutic target regions and potential strategies for rabies treatment.
Topics: Animals; Host-Pathogen Interactions; Humans; Immune Evasion; Rabies virus; Virus Replication
PubMed: 27548204
DOI: 10.3390/v8080231 -
Viruses Dec 2021Vesicular stomatitis virus (VSV), the founding member of the mononegavirus order (), was found to be a negative strand RNA virus in the 1960s, and since then the number... (Review)
Review
Vesicular stomatitis virus (VSV), the founding member of the mononegavirus order (), was found to be a negative strand RNA virus in the 1960s, and since then the number of such viruses has continually increased with no end in sight. Sendai virus (SeV) was noted soon afterwards due to an outbreak of newborn pneumonitis in Japan whose putative agent was passed in mice, and nowadays this mouse virus is mainly the bane of animal houses and immunologists. However, SeV was important in the study of this class of viruses because, like flu, it grows to high titers in embryonated chicken eggs, facilitating the biochemical characterization of its infection and that of its nucleocapsid, which is very close to that of measles virus (MeV). This review and opinion piece follow SeV as more is known about how various mononegaviruses express their genetic information and carry out their RNA synthesis, and proposes a unified model based on what all MNV have in common.
Topics: Animals; Genome, Viral; Humans; Mononegavirales; Mononegavirales Infections; RNA, Viral; Respirovirus Infections; Sendai virus
PubMed: 34960735
DOI: 10.3390/v13122466 -
Viruses Dec 2014We review the molecular and epidemiological characteristics of cetacean morbillivirus (CeMV) and the diagnosis and pathogenesis of associated disease, with six different... (Review)
Review
We review the molecular and epidemiological characteristics of cetacean morbillivirus (CeMV) and the diagnosis and pathogenesis of associated disease, with six different strains detected in cetaceans worldwide. CeMV has caused epidemics with high mortality in odontocetes in Europe, the USA and Australia. It represents a distinct species within the Morbillivirus genus. Although most CeMV strains are phylogenetically closely related, recent data indicate that morbilliviruses recovered from Indo-Pacific bottlenose dolphins (Tursiops aduncus), from Western Australia, and a Guiana dolphin (Sotalia guianensis), from Brazil, are divergent. The signaling lymphocyte activation molecule (SLAM) cell receptor for CeMV has been characterized in cetaceans. It shares higher amino acid identity with the ruminant SLAM than with the receptors of carnivores or humans, reflecting the evolutionary history of these mammalian taxa. In Delphinidae, three amino acid substitutions may result in a higher affinity for the virus. Infection is diagnosed by histology, immunohistochemistry, virus isolation, RT-PCR, and serology. Classical CeMV-associated lesions include bronchointerstitial pneumonia, encephalitis, syncytia, and lymphoid depletion associated with immunosuppression. Cetaceans that survive the acute disease may develop fatal secondary infections and chronic encephalitis. Endemically infected, gregarious odontocetes probably serve as reservoirs and vectors. Transmission likely occurs through the inhalation of aerosolized virus but mother to fetus transmission was also reported.
Topics: Animals; Cetacea; Morbillivirus; Morbillivirus Infections; Phylogeny
PubMed: 25533660
DOI: 10.3390/v6125145 -
Virology Journal Dec 2019Marburg virus (MARV) is a highly pathogenic virus associated with severe disease and mortality rates as high as 90%. Outbreaks of MARV are sporadic, deadly, and often... (Review)
Review
Marburg virus (MARV) is a highly pathogenic virus associated with severe disease and mortality rates as high as 90%. Outbreaks of MARV are sporadic, deadly, and often characterized by a lack of resources and facilities to diagnose and treat patients. There are currently no approved vaccines or treatments, and the chaotic and infrequent nature of outbreaks, among other factors, makes testing new countermeasures during outbreaks ethically and logistically challenging. Without field efficacy studies, researchers must rely on animal models of MARV infection to assess the efficacy of vaccines and treatments, with the limitations being the accuracy of the animal model in recapitulating human pathogenesis. This review will compare various animal models to the available descriptions of human pathogenesis and aims to evaluate their effectiveness in modeling important aspects of Marburg virus disease.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Marburg Virus Disease; Marburgvirus
PubMed: 31888676
DOI: 10.1186/s12985-019-1272-z