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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 -
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 -
MBio Feb 2023Human metapneumovirus (HMPV) is one of the leading causes of respiratory illness (RI), primarily in infants. Worldwide, two genetic lineages (A and B) of HMPV are...
Human metapneumovirus (HMPV) is one of the leading causes of respiratory illness (RI), primarily in infants. Worldwide, two genetic lineages (A and B) of HMPV are circulating that are antigenically distinct and can each be further divided into genetic sublineages. Surveillance combined with large-scale whole-genome sequencing studies of HMPV are scarce but would help to identify viral evolutionary dynamics. Here, we analyzed 130 whole HMPV genome sequences obtained from samples collected from individuals hospitalized with RI and partial fusion ( = 144) and attachment ( = 123) protein gene sequences obtained from samples collected from patients with RI visiting general practitioners between 2005 and 2021 in the Netherlands. Phylogenetic analyses demonstrated that HMPV continued to group in the four sublineages described in 2004 (A1, A2, B1, and B2). However, one sublineage (A1) was no longer detected in the Netherlands after 2006, while the others continued to evolve. No differences were observed in dominant (sub)lineages between samples obtained from patients with RI being hospitalized and those consulting general practitioners. In both populations, viruses of lineage A2 carrying a 180-nucleotide or 111-nucleotide duplication in the attachment protein gene became the most frequently detected genotypes. In the past, different names for the newly energing lineages have been proposed, demonstrating the need for a consistent naming convention. Here, criteria are proposed for the designation of new genetic lineages to aid in moving toward a systematic HMPV classification. Human metapneumovirus (HMPV) is one of the major causative agents of human respiratory tract infections. Monitoring of virus evolution could aid toward the development of new antiviral treatments or vaccine designs. Here, we studied HMPV evolution between 2005 and 2021, with viruses obtained from samples collected from hospitalized individuals and patients with respiratory infections consulting general practitioners. Phylogenetic analyses demonstrated that HMPV continued to group in the four previously described sublineages (A1, A2, B1, and B2). However, one sublineage (A1) was no longer detected after 2006, while the others continued to evolve. No differences were observed in dominant (sub)lineages between patients being hospitalized and those consulting general practitioners. In both populations, viruses of lineage A2 carrying a 180-nucleotide or 111-nucleotide duplication in the attachment protein gene became the most frequently detected genotypes. These data were used to propose criteria for the designation of new genetic lineages to aid toward a systematic HMPV classification.
Topics: Infant; Humans; Metapneumovirus; Paramyxoviridae Infections; Phylogeny; Genetic Variation; Respiratory Tract Infections; Genotype; Nucleotides
PubMed: 36507832
DOI: 10.1128/mbio.02280-22 -
Medicine Oct 2023Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections are common in children worldwide. However, the clinical factors related to extended...
Clinical factors associated with extended hospitalization in pediatric patients ≥3 years of age with respiratory syncytial virus or human metapneumovirus infection: A Japanese single-center, retrospective study.
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections are common in children worldwide. However, the clinical factors related to extended hospitalization in Japanese patients aged ≥3 years remain elusive. We aimed to elucidate the clinical risk factors contributing to hospital stays ≥7 days in patients with RSV and hMPV infections. Patients ≥3 years of age who were hospitalized due to RSV or hMPV infection between 2014 to 2020 were included. Twenty-one RSV- and 27 hMPV-infected patients were enrolled. Patients were divided into 2 groups: hospitalization for ≥ and <7 days. Univariate and multivariate analyses determined the clinical risk factors contributing to hospital stay ≥7 days. The RSV- and hMPV-infected patients had similar clinical characteristics. The clinical risk factors contributing to extended hospitalization were analyzed in the 48 infected patients of the 2 groups. The presence of prophylactic antibiotics usage, co-bacterial colonization, and underlying diseases were extracted by univariate analysis (P < .05). In multivariate analysis, underlying diseases were determined as an independent clinical risk factor (odds ratio 8.09, P = .005). Underlying diseases contributed to extended hospitalization in RSV- or hMPV-infected patients ≥3 years of age.
Topics: Child; Child, Preschool; Humans; Infant; Comorbidity; East Asian People; Hospitalization; Length of Stay; Metapneumovirus; Paramyxoviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Retrospective Studies; Japan
PubMed: 37861549
DOI: 10.1097/MD.0000000000035565 -
Molekuliarnaia Biologiia 2018Preclinical studies demonstrate that a broad spectrum of human and animal malignant cells can be killed by oncolytic paramyxoviruses, which includes cells of ecto-,... (Review)
Review
Preclinical studies demonstrate that a broad spectrum of human and animal malignant cells can be killed by oncolytic paramyxoviruses, which includes cells of ecto-, endo- and mesodermal origin. In clinical trials, significant reduction or even complete elimination of primary tumors and established metastases has been reported. Different routes of virus administration (intratumoral, intravenous, intradermal, intraperito-neal, or intrapleural) and single- vs. multiple-dose administration schemes have been explored. The reported side effects were grades 1 and 2, with the most common among them being mild fever. There are certain advantages in using paramyxoviruses as oncolytic agents compared to members of other virus families exist. Thanks to cytoplasmic replication, paramyxoviruses do not integrate the host genome or engage in recombination, which makes them safer and more attractive candidates for widely used therapeutic oncolysis than ret-roviruses or some DNA viruses. The list of oncolytic Paramyxoviridae members includes the attenuated measles virus, mumps virus, low pathogenic Newcastle disease, and Sendai viruses. Metastatic cancer cells frequently overexpress certain surface molecules that can serve as receptors for oncolytic paramyxoviruses. This promotes specific viral attachment to these malignant cells. Paramyxoviruses are capable of inducing efficient syncytium-mediated lysis of cancer cells and elicit strong immune stimulation, which dramatically enforces anticancer immune surveillance. In general, preclinical studies and phases I-III of clinical trials yield very encouraging results and warrant continued research of oncolytic paramyxoviruses as a particularly valuable addition to the existing panel of cancer-fighting approaches.
Topics: Animals; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Paramyxoviridae
PubMed: 29989571
DOI: 10.7868/S0026898418030023 -
Frontiers in Cellular and Infection... 2023Nipah virus (NiV) and Hendra virus (HeV) are newly emerging dangerous zoonotic pathogens of the genus of the family. NiV and HeV (HNVs) which are transmitted by bats...
Nipah virus (NiV) and Hendra virus (HeV) are newly emerging dangerous zoonotic pathogens of the genus of the family. NiV and HeV (HNVs) which are transmitted by bats cause acute respiratory disease and fatal encephalitis in humans. To date, as there is a lack of antiviral drugs or effective antiviral therapies, the development of vaccines against those two viruses is of primary importance, and the immunogen design is crucial to the success of vaccines. In this study, the full-length protein (G), the ectodomain (Ge) and the head domain (Gs) of NiV attachment glycoprotein were delivered by the replication-defective type 5 adenovirus vector (Ad5) respectively, and the recombinant Ad5-NiV vaccine candidates (Ad5-NiVG, Ad5-NiVGe and Ad5-NiVGs) were constructed and their immunogenicity were evaluated in mice. The results showed that all the vaccine candidates stimulated specific humoral and cellular immune responses efficiently and rapidly against both NiV and HeV, and the Ad5-NiVGe elicited the strongest immune responses after a single-dose immunization. Furthermore, the potent conserved T-cell epitope DTLYFPAVGFL shared by NiV and HeV was identified in the study, which may provide valid information on the mechanism of HNVs-specific cellular immunity. In summary, this study demonstrates that the Ad5-NiVGe could be a potent vaccine candidate against HNVs by inducing robust humoral and cellular immune responses.
Topics: Humans; Animals; Mice; Hendra Virus; Nipah Virus; Virus Attachment; Glycoproteins; Vaccines, Synthetic; Immunity, Cellular; Adenoviridae
PubMed: 37577376
DOI: 10.3389/fcimb.2023.1180344 -
Cellular and Molecular Life Sciences :... Sep 2017In this review, we summarize computational and experimental data gathered so far showing that structural disorder is abundant within paramyxoviral nucleoproteins (N) and... (Review)
Review
In this review, we summarize computational and experimental data gathered so far showing that structural disorder is abundant within paramyxoviral nucleoproteins (N) and phosphoproteins (P). In particular, we focus on measles, Nipah, and Hendra viruses and highlight both commonalities and differences with respect to the closely related Sendai virus. The molecular mechanisms that control the disorder-to-order transition undergone by the intrinsically disordered C-terminal domain (N) of their N proteins upon binding to the C-terminal X domain (XD) of the homologous P proteins are described in detail. By having a significant residual disorder, N-XD complexes are illustrative examples of "fuzziness", whose possible functional significance is discussed. Finally, the relevance of N-P interactions as promising targets for innovative antiviral approaches is underscored, and the functional advantages of structural disorder for paramyxoviruses are pinpointed.
Topics: Antiviral Agents; Evolution, Molecular; Intrinsically Disordered Proteins; Molecular Chaperones; Nucleoproteins; Paramyxoviridae; Phosphoproteins; Protein Structure, Quaternary; RNA, Viral; Viral Proteins; Virus Replication
PubMed: 28600653
DOI: 10.1007/s00018-017-2556-3