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Advances in Experimental Medicine and... 2015In this review we summarize available data showing the abundance of structural disorder within the nucleoprotein (N) and phosphoprotein (P) from three paramyxoviruses,... (Review)
Review
In this review we summarize available data showing the abundance of structural disorder within the nucleoprotein (N) and phosphoprotein (P) from three paramyxoviruses, namely the measles (MeV), Nipah (NiV) and Hendra (HeV) viruses. We 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 P proteins. We also show that a significant flexibility persists within NTAIL-XD complexes, which therefore provide illustrative examples of "fuzziness". The functional implications of structural disorder for viral transcription and replication are discussed in light of the ability of disordered regions to establish a complex molecular partnership and to confer a considerable reach to the elements of the replicative machinery.
Topics: Intrinsically Disordered Proteins; Paramyxoviridae; Protein Conformation; Viral Proteins; Virus Replication
PubMed: 26387109
DOI: 10.1007/978-3-319-20164-1_12 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Sep 2018Newcastle disease virus is paramyxoviridae, Avian mumps virus genus type I, and infects more than 250 species of birds, causing huge losses on poultry farming worldwide.... (Review)
Review
Newcastle disease virus is paramyxoviridae, Avian mumps virus genus type I, and infects more than 250 species of birds, causing huge losses on poultry farming worldwide. Numerous experiments have demonstrated that Newcastle disease virus has oncolytic activity on tumor cells and can selectively replicate in cancer cells. Thus, Newcastle disease virus is a potential therapeutic agent for cancer treatment. Some human clinical trials achieved good results. In this review, we summarized research progress of the relationship between the structural protein of Newcastle disease virus and virulence, anti-tumor and autophagy of Newcastle disease.
Topics: Animals; Autophagy; Birds; Humans; Neoplasms; Newcastle disease virus; Oncolytic Virotherapy; Viral Structural Proteins
PubMed: 30255677
DOI: 10.13345/j.cjb.180153 -
Journal of Virology Feb 2024Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the genus, NiV and HeV use an...
Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the genus, NiV and HeV use an attachment (G) glycoprotein and a class I fusion (F) glycoprotein to invade host cells. The F protein rearranges from a metastable prefusion form to an extended postfusion form to facilitate host cell entry. Prefusion NiV F elicits higher neutralizing antibody titers than postfusion NiV F, indicating that stabilization of prefusion F may aid vaccine development. A combination of amino acid substitutions (L104C/I114C, L172F, and S191P) is known to stabilize NiV F in its prefusion conformation, although the extent to which substitutions transfer to other henipavirus F proteins is not known. Here, we perform biophysical and structural studies to investigate the mechanism of prefusion stabilization in F proteins from three henipaviruses: NiV, HeV, and Langya virus (LayV). Three known stabilizing substitutions from NiV F transfer to HeV F and exert similar structural and functional effects. One engineered disulfide bond, located near the fusion peptide, is sufficient to stabilize the prefusion conformations of both HeV F and LayV F. Although LayV F shares low overall sequence identity with NiV F and HeV F, the region around the fusion peptide exhibits high sequence conservation across all henipaviruses. Our findings indicate that substitutions targeting this site of conformational change might be applicable to prefusion stabilization of other henipavirus F proteins and support the use of NiV as a prototypical pathogen for henipavirus vaccine antigen design.IMPORTANCEPathogenic henipaviruses such as Nipah virus (NiV) and Hendra virus (HeV) cause respiratory symptoms, with severe cases resulting in encephalitis, seizures, and coma. The work described here shows that the NiV and HeV fusion (F) proteins share common structural features with the F protein from an emerging henipavirus Langya virus (LayV). Sequence alignment alone was sufficient to predict which known prefusion-stabilizing amino acid substitutions from NiV F would stabilize the prefusion conformations of HeV F and LayV F. This work also reveals an unexpected oligomeric interface shared by prefusion HeV F and NiV F. Together, these advances lay a foundation for future antigen design targeting henipavirus F proteins. In this way, Nipah virus can serve as a prototypical pathogen for the development of protective vaccines and monoclonal antibodies to prepare for potential henipavirus outbreaks.
Topics: Humans; Glycoproteins; Hendra Virus; Henipavirus; Henipavirus Infections; Nipah Virus; Peptides; Viral Fusion Proteins; Viral Proteins
PubMed: 38214525
DOI: 10.1128/jvi.01372-23 -
Avian Pathology : Journal of the W.V.P.A Aug 2019To date, four subgroups of avian metapneumoviruses have been defined (AMPV-A, B, C and D) based on genetic and antigenic differences. The extent of infection in the...
To date, four subgroups of avian metapneumoviruses have been defined (AMPV-A, B, C and D) based on genetic and antigenic differences. The extent of infection in the three principal species (turkeys, chickens and ducks) by these subgroups is, however, not well defined. Here, a series of controlled and ethically approved experimental infections were performed in specific pathogen-free turkeys, chickens and ducks with each of the four AMPV subgroups. For subgroup C, one strain isolated from turkeys in the USA (turkey AMPV-C) and one isolated from ducks in France (duck AMPV-C) were compared. Globally, these extensive experimental trials demonstrated that AMPV-A, B, turkey C and D were well adapted to Galliformes, especially turkeys; however, chickens showed limited clinical signs and differences in seroconversion and transmission. Notably, chickens did not transmit AMPV-A to contacts and were shown for the first time to be susceptible to AMPV-D. The duck AMPV-C was well adapted to ducks; however, chickens and turkeys seroconverted and were positive by virus isolation. In addition, seroconversion of contact turkeys to duck AMPV-C demonstrated horizontal transmission of this virus in a non-palmiped species under our experimental conditions. Interestingly, in chickens and turkeys, duck AMPV-C isolation was possible despite a lack of detection of viral RNA. Likewise, the turkey AMPV-C virus was well adapted to turkeys yet was also isolated from chickens despite a lack of detection of viral RNA. These results would suggest a selection for viral genetic sequences that differ from the original strain upon adaptation to a 'non-conventional host'.
Topics: Animals; Antibodies, Viral; Chick Embryo; Chickens; Chlorocebus aethiops; Ducks; Host Specificity; Metapneumovirus; Paramyxoviridae Infections; Poultry Diseases; RNA, Viral; Real-Time Polymerase Chain Reaction; Serial Passage; Specific Pathogen-Free Organisms; Turkeys; Vero Cells
PubMed: 30777452
DOI: 10.1080/03079457.2019.1584390 -
Virology Nov 2016The recent flurry of high resolution structures of Negative Strand RNA Virus RNA-dependent RNA polymerases has rekindled interest in the manner in which these... (Review)
Review
The recent flurry of high resolution structures of Negative Strand RNA Virus RNA-dependent RNA polymerases has rekindled interest in the manner in which these polymerases, and in particular those of the nonsegmented viruses, recognize the RNA sequences that control mRNA synthesis and genome replication. In the light of these polymerase structures, we re-examine some unusual aspects of the Paramyxoviridae, namely bipartite replication promoters and mRNA editing, and the manner in which these properties are governed by genome hexamer phase.
Topics: 3' Untranslated Regions; Animals; Gene Expression Regulation, Viral; Genome, Viral; Humans; Paramyxoviridae; Promoter Regions, Genetic; RNA Editing; RNA, Messenger; RNA, Viral; Transcription, Genetic; Viral Proteins
PubMed: 27567257
DOI: 10.1016/j.virol.2016.08.018 -
Essays in Biochemistry Dec 2022Measles, Nipah and Hendra viruses are severe human pathogens within the Paramyxoviridae family. Their non-segmented, single-stranded, negative-sense RNA genome is... (Review)
Review
Measles, Nipah and Hendra viruses are severe human pathogens within the Paramyxoviridae family. Their non-segmented, single-stranded, negative-sense RNA genome is encapsidated by the nucleoprotein (N) within a helical nucleocapsid that is the substrate used by the viral RNA-dependent-RNA-polymerase (RpRd) for transcription and replication. The RpRd is a complex made of the large protein (L) and of the phosphoprotein (P), the latter serving as an obligate polymerase cofactor and as a chaperon for N. Both the N and P proteins are enriched in intrinsically disordered regions (IDRs), i.e. regions devoid of stable secondary and tertiary structure. N possesses a C-terminal IDR (NTAIL), while P consists of a large, intrinsically disordered N-terminal domain (NTD) and a C-terminal domain (CTD) encompassing alternating disordered and ordered regions. The V and W proteins, two non-structural proteins that are encoded by the P gene via a mechanism of co-transcriptional edition of the P mRNA, are prevalently disordered too, sharing with P the disordered NTD. They are key players in the evasion of the host antiviral response and were shown to phase separate and to form amyloid-like fibrils in vitro. In this review, we summarize the available information on IDRs within the N, P, V and W proteins from these three model paramyxoviruses and describe their molecular partnership. We discuss the functional benefit of disorder to virus replication in light of the critical role of IDRs in affording promiscuity, multifunctionality, fine regulation of interaction strength, scaffolding functions and in promoting liquid-liquid phase separation and fibrillation.
Topics: Hendra Virus; Nucleoproteins; RNA; Virus Replication; Measles virus; Nipah Virus
PubMed: 36148633
DOI: 10.1042/EBC20220045 -
Viruses Jan 2022Particles of many paramyxoviruses include small amounts of proteins with a molecular weight of about 20 kDa. These proteins, termed "C", are basic, have low amino acid... (Review)
Review
Particles of many paramyxoviruses include small amounts of proteins with a molecular weight of about 20 kDa. These proteins, termed "C", are basic, have low amino acid homology and some secondary structure conservation. C proteins are encoded in alternative reading frames of the phosphoprotein gene. Some viruses express nested sets of C proteins that exert their functions in different locations: In the nucleus, they interfere with cellular transcription factors that elicit innate immune responses; in the cytoplasm, they associate with viral ribonucleocapsids and control polymerase processivity and orderly replication, thereby minimizing the activation of innate immunity. In addition, certain C proteins can directly bind to, and interfere with the function of, several cytoplasmic proteins required for interferon induction, interferon signaling and inflammation. Some C proteins are also required for efficient virus particle assembly and budding. C-deficient viruses can be grown in certain transformed cell lines but are not pathogenic in natural hosts. C proteins affect the same host functions as other phosphoprotein gene-encoded proteins named V but use different strategies for this purpose. Multiple independent systems to counteract host defenses may ensure efficient immune evasion and facilitate virus adaptation to new hosts and tissue environments.
Topics: Animals; Defective Interfering Viruses; Genome, Viral; Humans; Immune Evasion; Immunity, Innate; Inflammasomes; Open Reading Frames; Paramyxoviridae Infections; Paramyxovirinae; Phosphoproteins; Phylogeny; Viral Proteins; Virus Assembly; Virus Replication
PubMed: 35062341
DOI: 10.3390/v14010137 -
Clinical Features of Human Metapneumovirus-Associated Community-acquired Pneumonia Hospitalizations.Clinical Infectious Diseases : An... Jan 2021Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated...
BACKGROUND
Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated pneumonia with other pathogens.
METHODS
Active, population-based surveillance was previously conducted for radiographically confirmed, community-acquired pneumonia hospitalizations among children and adults in 8 United States hospitals. Clinical data and specimens for pathogen detection were systematically collected. We described clinical features of all HMPV-associated pneumonia and, after excluding codetections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled the severity (mild, moderate, and severe) and length of stay using multivariable proportional odds regression.
RESULTS
HMPV was detected in 298/2358 (12.6%) children and 88/2320 (3.8%) adults hospitalized with pneumonia and was commonly codetected with other pathogens (125/298 [42%] children and 21/88 [24%] adults). Fever and cough were the most common presenting symptoms of HMPV-associated pneumonia and were also common symptoms of other pathogens. After excluding codetections in children (n = 1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.43-9.40), respiratory syncytial virus (RSV; OR, 0.76; 95% CI, .59-.99) and atypical (OR, 0.39; 95% CI, .19-.81) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (OR, 0.88; 95% CI, .55-1.39). In adults (n = 2145), bacterial (OR, 3.74; 95% CI, 1.87-7.47) and RSV pneumonia (OR, 1.82; 95% CI, 1.32-2.50) were more severe than HMPV (reference), but all other pathogens had similar severity.
CONCLUSIONS
Clinical features did not reliably distinguish HMPV-associated pneumonia from other pathogens. HMPV-associated pneumonia was less severe than bacterial and adult RSV pneumonia, but was otherwise as or more severe than other common pathogens.
Topics: Adult; Child; Hospitalization; Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Pneumonia, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 32010955
DOI: 10.1093/cid/ciaa088 -
Revista Da Sociedade Brasileira de... 2018Infections caused by respiratory viruses are important problems worldwide, especially in children. Human metapneumovirus (hMPV) is a respiratory pathogen and causes... (Comparative Study)
Comparative Study
INTRODUCTION
Infections caused by respiratory viruses are important problems worldwide, especially in children. Human metapneumovirus (hMPV) is a respiratory pathogen and causes severe infections with nonspecific symptoms. This study reports the hMPV occurrence and dissemination in southern Brazil and compares the frequency of occurrence of this virus and the human respiratory syncytial virus (hRSV) in the epidemiological weeks in a three-year period (2009-2011).
METHODS
In total, 545 nasopharyngeal (NP) specimens from individuals with Severe Acute Respiratory Syndrome (SARS) who were negative for other seven respiratory viruses were analyzed for the presence of hMPV. Human metapneumovirus was detected by direct immunofluorescence and real-time reverse transcription polymerase chain reaction.
RESULTS
hMPV was detected in 109 patients from the main geographic regions of the southernmost state of Brazil, presenting similar overall prevalence in males (46.8%) and females (53.2%). Among children who were less than six years old, hMPV was detected in 99 samples of all age groups, with a higher frequency in infants who were less than one year old (45.7%) compared to all other age groups until six years. hMPV and hRSV infection occurred in almost the same epidemiological weeks (EWs) of each year, with peaks of incidence between EW 31/37 and EW 26/38 for the years 2009 and 2011, respectively. hMPV was further detected in several cases of SARS and it was the only virus detected in three deaths.
CONCLUSIONS
These findings indicate that hMPV is in circulation in southern Brazil and highlight the importance of diagnosing hMPV for influenza-like illness in the population.
Topics: Acute Disease; Adolescent; Adult; Brazil; Child; Child, Preschool; Female; Fluorescent Antibody Technique, Direct; Humans; Infant; Infant, Newborn; Male; Metapneumovirus; Middle Aged; Nasopharynx; Paramyxoviridae Infections; Prevalence; Real-Time Polymerase Chain Reaction; Respiratory Distress Syndrome; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Severity of Illness Index; Young Adult
PubMed: 29513839
DOI: 10.1590/0037-8682-0435-2017 -
Viruses Jun 2019Canine distemper virus (CDV) is a worldwide distributed virus which belongs to the genus within the family. CDV spreads through the lymphatic, epithelial, and nervous... (Review)
Review
Canine distemper virus (CDV) is a worldwide distributed virus which belongs to the genus within the family. CDV spreads through the lymphatic, epithelial, and nervous systems of domestic dogs and wildlife, in at least six orders and over 20 families of mammals. Due to the high morbidity and mortality rates and broad host range, understanding the epidemiology of CDV is not only important for its control in domestic animals, but also for the development of reliable wildlife conservation strategies. The present review aims to give an outlook of the multiple evolutionary landscapes and factors involved in the transmission of CDV by including epidemiological data from multiple species in urban, wild and peri-urban settings, not only in domestic animal populations but at the wildlife interface. It is clear that different epidemiological scenarios can lead to the presence of CDV in wildlife even in the absence of infection in domestic populations, highlighting the role of CDV in different domestic or wild species without clinical signs of disease mainly acting as reservoirs (peridomestic and mesocarnivores) that are often found in peridomestic habits triggering CDV epidemics. Another scenario is driven by mutations, which generate genetic variation on which random drift and natural selection can act, shaping the genetic structure of CDV populations leading to some fitness compensations between hosts and driving the evolution of specialist and generalist traits in CDV populations. In this scenario, the highly variable protein hemagglutinin (H) determines the cellular and host tropism by binding to signaling lymphocytic activation molecule (SLAM) and nectin-4 receptors of the host; however, the multiple evolutionary events that may have facilitated CDV adaptation to different hosts must be evaluated by complete genome sequencing. This review is focused on the study of CDV interspecies transmission by examining molecular and epidemiological reports based on sequences of the hemagglutinin gene and the growing body of studies of the complete genome; emphasizing the importance of long-term multidisciplinary research that tracks CDV in the presence or absence of clinical signs in wild species, and helping to implement strategies to mitigate the infection. Integrated research incorporating the experience of wildlife managers, behavioral and conservation biologists, veterinarians, virologists, and immunologists (among other scientific areas) and the inclusion of several wild and domestic species is essential for understanding the intricate epidemiological dynamics of CDV in its multiple host infections.
Topics: Animals; Animals, Wild; Distemper; Distemper Virus, Canine; Dogs; Evolution, Molecular; Host Specificity; Phylogeny
PubMed: 31247987
DOI: 10.3390/v11070582