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Proceedings of the National Academy of... Mar 2009The matrix protein (M) of respiratory syncytial virus (RSV), the prototype viral member of the Pneumovirinae (family Paramyxoviridae, order Mononegavirales), has been...
The matrix protein (M) of respiratory syncytial virus (RSV), the prototype viral member of the Pneumovirinae (family Paramyxoviridae, order Mononegavirales), has been crystallized and the structure determined to a resolution of 1.6 A. The structure comprises 2 compact beta-rich domains connected by a relatively unstructured linker region. Due to the high degree of side-chain order in the structure, an extensive contiguous area of positive surface charge covering approximately 600 A(2) can be resolved. This unusually large patch of positive surface potential spans both domains and the linker, and provides a mechanism for driving the interaction of the protein with a negatively-charged membrane surface or other virion components such as the nucleocapsid. This patch is complemented by regions of high hydrophobicity and a striking planar arrangement of tyrosine residues encircling the C-terminal domain. Comparison of the RSV M sequence with other members of the Pneumovirinae shows that regions of divergence correspond to surface exposed loops in the M structure, with the majority of viral species-specific differences occurring in the N-terminal domain.
Topics: Cell Membrane; Crystallization; Crystallography, X-Ray; Hydrophobic and Hydrophilic Interactions; Mononegavirales; Protein Conformation; Respiratory Syncytial Viruses; Static Electricity; Viral Matrix Proteins; Viral Proteins
PubMed: 19251668
DOI: 10.1073/pnas.0805740106 -
Current Opinion in Immunology Aug 2022Viral proteins fold into a variety of structures as they perform their functions. Structure-based vaccine design aims to exploit knowledge of an antigen's architecture... (Review)
Review
Viral proteins fold into a variety of structures as they perform their functions. Structure-based vaccine design aims to exploit knowledge of an antigen's architecture to stabilize it in a vulnerable conformation. We summarize the general principles of structure-based vaccine design, with a focus on the major types of sequence modifications: proline, disulfide, cavity-filling, electrostatic and hydrogen-bond substitution, as well as domain deletion. We then review recent applications of these principles to vaccine-design efforts across five viral families: Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, and Filoviridae. Outstanding challenges include continued application of proven design principles to pathogens of interest, as well as development of new strategies for those pathogens that resist traditional techniques.
Topics: Coronaviridae; Filoviridae; Humans; Orthomyxoviridae; Paramyxoviridae; Pneumovirinae; Vaccine Development; Viral Proteins; Viral Vaccines
PubMed: 35598506
DOI: 10.1016/j.coi.2022.102209 -
The Journal of General Virology Nov 2021is a family of viruses in the order , with unsegmented (except for members of the genus ), negative-sense RNA genomes of 10-13 kb. Nyamviruses have a genome...
is a family of viruses in the order , with unsegmented (except for members of the genus ), negative-sense RNA genomes of 10-13 kb. Nyamviruses have a genome organisation and content similar to that of other mononegaviruses. includes several genera that form monophyletic clades on phylogenetic analysis of the RNA polymerase. Nyamiviruses have been found associated with diverse invertebrates as well as land- and seabirds. Members of the genera and produce enveloped, spherical virions. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family which is available at ictv.global/report/nyamiviridae.
Topics: Animals; Genome, Viral; Invertebrates; Mononegavirales; Phylogeny; RNA, Viral; Viral Proteins; Virion
PubMed: 34738886
DOI: 10.1099/jgv.0.001681 -
Viruses Jan 2023The order contains a variety of highly pathogenic viruses that may infect humans, including the families , , , and . Animal models have historically been important to... (Review)
Review
The order contains a variety of highly pathogenic viruses that may infect humans, including the families , , , and . Animal models have historically been important to study virus pathogenicity and to develop medical countermeasures. As these have inherent shortcomings, the rise of microphysiological systems and organoids able to recapitulate hallmarks of the diseases caused by these viruses may have enormous potential to add to or partially replace animal modeling in the future. Indeed, microphysiological systems and organoids are already used in the pharmaceutical R&D pipeline because they are prefigured to overcome the translational gap between model systems and clinical studies. Moreover, they may serve to alleviate ethical concerns related to animal research. In this review, we discuss the value of animal model alternatives in human pathogenic filovirus and bornavirus research. The current animal models and their limitations are presented followed by an overview of existing alternatives, such as organoids and microphysiological systems, which might help answering open research questions.
Topics: Animals; Humans; Filoviridae; Bornaviridae; Models, Animal
PubMed: 36680198
DOI: 10.3390/v15010158 -
The Journal of Infectious Diseases Nov 2023Vesicular stomatitis virus-Ebola virus (VSV-EBOV) vaccine has been successfully used in ring vaccination approaches during EBOV disease outbreaks demonstrating its...
Vesicular stomatitis virus-Ebola virus (VSV-EBOV) vaccine has been successfully used in ring vaccination approaches during EBOV disease outbreaks demonstrating its general benefit in short-term prophylactic vaccination, but actual proof of its benefit in true postexposure prophylaxis (PEP) for humans is missing. Animal studies have indicated PEP efficacy when VSV-EBOV was used within hours of lethal EBOV challenge. Here, we used a lower EBOV challenge dose and a combined intravenous and intramuscular VSV-EBOV administration to improve PEP efficacy in the rhesus macaque model. VSV-EBOV treatment 1 hour after EBOV challenge resulted in delayed disease progression but little benefit in outcome. Thus, we could not confirm previous results indicating questionable benefit of VSV-EBOV for EBOV PEP in a nonhuman primate model.
Topics: Humans; Animals; Ebolavirus; Macaca mulatta; Hemorrhagic Fever, Ebola; Vesiculovirus; Vesicular stomatitis Indiana virus; Ebola Vaccines
PubMed: 37474155
DOI: 10.1093/infdis/jiad280 -
Trends in Biochemical Sciences May 2002The Mononegavirales virus group comprises several major human pathogens, including measles, rabies and Ebola viruses. This article reports a computational analysis of...
The Mononegavirales virus group comprises several major human pathogens, including measles, rabies and Ebola viruses. This article reports a computational analysis of the C-terminal region of RNA-dependent RNA-polymerases from Mononegavirales. Using a combination of sequence similarity and threading analysis, a 2'-O-ribose methyltransferase domain was identified that is involved in the capping of viral mRNAs.
Topics: Amino Acid Sequence; DNA-Directed RNA Polymerases; Humans; Methyltransferases; Molecular Sequence Data; Mononegavirales; Protein Structure, Tertiary; RNA Caps; RNA Processing, Post-Transcriptional; RNA, Viral; Sequence Alignment
PubMed: 12076527
DOI: 10.1016/s0968-0004(02)02091-1 -
Current Topics in Microbiology and... 2009Measles virus belongs to the Paramyxoviridae family within the Mononegavirales order. Its nonsegmented, single-stranded, negative-sense RNA genome is encapsidated by the... (Review)
Review
Measles virus belongs to the Paramyxoviridae family within the Mononegavirales order. Its nonsegmented, single-stranded, negative-sense RNA genome is encapsidated by the nucleoprotein (N) to form a helical nucleocapsid. This ribonucleoproteic complex is the substrate for both transcription and replication. The RNA-dependent RNA polymerase binds to the nucleocapsid template via its co-factor, the phosphoprotein (P). This chapter describes the main structural information available on the nucleoprotein, showing that it consists of a structured core (N(CORE)) and an intrinsically disordered C-terminal domain (N(TAIL)). We propose a model where the dynamic breaking and reforming of the interaction between N(TAIL) and P would allow the polymerase complex (L-P) to cartwheel on the nucleocapsid template. We also propose a model where the flexibility of the disordered N and P domains allows the formation of a tripartite complex (No-P-L) during replication, followed by the delivery of N monomers to the newly synthesized genomic RNA chain. Finally, the functional implications of structural disorder are also discussed in light of the ability of disordered regions to establish interactions with multiple partners, thus leading to multiple biological effects.
Topics: Animals; Humans; Measles; Measles virus; Nucleocapsid; Nucleocapsid Proteins; Protein Binding; Protein Structure, Tertiary; Virus Replication
PubMed: 19198564
DOI: 10.1007/978-3-540-70523-9_6 -
Revista Chilena de Infectologia :... 2018With the apparition of the crazy cows disease at the end of twentieth century, great was the temptation for denominate "crazy horses disease" an ancient enzootic...
With the apparition of the crazy cows disease at the end of twentieth century, great was the temptation for denominate "crazy horses disease" an ancient enzootic encephalo-myelitis, known from the 17th century and now named "Borna disease" in 1970, because severe outbreaks affecting horses in this city of Germany since 1885. But the sickness was not a prion disease but a viral one, causing also encephalopathy in several other animal species. After seventy years of investigation, the finding of the virus in human patients with psychiatric pathology in the eighties gave an incentive to work harder, and the genome structure of the so called Bornavirus was completely described. Recently, japanese investigators found that elements homologous to the nucleoprotein (N) gene of Bornavirus exist in the genomes of several mammalian species, including humans, in which these sequences have been designated endogenous Borna-like N (EBLN) elements. And now the question is what they are doing there since their integration two million years ago.
Topics: Animals; Bornaviridae; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; Horse Diseases; Horses; Mononegavirales Infections
PubMed: 31095192
DOI: 10.4067/S0716-10182018000600700 -
The Veterinary Clinics of North... Dec 2000Borna disease is a sporadically occurring, progressive viral polioencephalomyelitis that primarily affects horses and sheep. The etiological agent, Borna disease virus... (Review)
Review
Borna disease is a sporadically occurring, progressive viral polioencephalomyelitis that primarily affects horses and sheep. The etiological agent, Borna disease virus (BDV), is an enveloped, single-stranded RNA virus that has been classified in the new virus family Bornaviridae within the order Mononegavirales. Serological evidence of BDV infection has been found in an increasing number of countries throughout the world. After an incubation period lasting a few weeks to several months, BDV infection can cause locomotor and sensory dysfunction followed by paralysis and death. Borna disease is the result of a virus-induced immunopathological reaction. BDV-specific antibodies and viral RNA have been found in humans with various psychiatric disorders.
Topics: Animals; Antibodies, Viral; Borna Disease; Borna disease virus; Horse Diseases; Horses
PubMed: 11219351
DOI: 10.1016/s0749-0739(17)30097-4 -
Trends in Microbiology Nov 2013Viruses of the Mononegavirales have helical nucleocapsids containing a single-stranded negative-sense RNA genome complexed with the nucleoprotein and several other... (Comparative Study)
Comparative Study Review
Viruses of the Mononegavirales have helical nucleocapsids containing a single-stranded negative-sense RNA genome complexed with the nucleoprotein and several other virus-encoded proteins. This RNA-protein complex acts as the template for replication and transcription during infection. Recent structural data has advanced our understanding of how these functions are achieved in filoviruses, which include dangerous pathogens such as Ebola virus. Polyploid filoviruses package multiple genome copies within strikingly long filamentous viral envelopes, which must be flexible to avoid breakage of the 19kb non-segmented genomic RNA. We review how the structure of filoviruses and paramyxoviruses permits this morphological flexibility in comparison to rhabdoviruses that have short, bullet-shaped virions with relatively rigid envelopes.
Topics: Filoviridae; Macromolecular Substances; Models, Biological; Models, Molecular; Nucleocapsid; Rhabdoviridae; Virus Assembly
PubMed: 24011860
DOI: 10.1016/j.tim.2013.08.001