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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 -
Vaccine Jan 2017Despite the recent explosion in RSV vaccine development, there remain substantial hurdles to overcome before licensing of effective vaccines will allow widespread use,... (Review)
Review
Despite the recent explosion in RSV vaccine development, there remain substantial hurdles to overcome before licensing of effective vaccines will allow widespread use, particularly in high-risk populations. Incomplete understanding of mechanisms and correlates of protection against RSV mean that, for the time being, successful RSV vaccines must directly demonstrate efficacy, which necessitates large and costly clinical trials in naturally infected patients. To mitigate the risks inherent in progressing to these late-stage trials, experimental human RSV infection studies have recently been re-established, representing the interface between pre-clinical models and observational studies of patients. Not only can they be used for early proof-of-concept clinical trials to test vaccine efficacy, but human challenge studies also offer the potential to better understand protective immunity against RSV infection to improve vaccine design and delivery. In the past, controlled human infection studies with RSV have been instrumental in elucidating the influence of factors such as route of infection and type of inoculum on the course of disease. Recently, efficacy trials of novel RSV antiviral drugs have also been successfully undertaken. Now, with advances in technology, detailed investigations of human mucosal immunity in the RSV-infected airway are possible. These have indicated defects in RSV-induced humoral and CD8+ T cell immunity that may contribute to the recurrent symptomatic infection that occurs throughout life and should be circumvented by optimal vaccines. Here, we discuss the insights derived from RSV human challenge models; the major impediments to their more widespread uptake; and their potential benefit in accelerating vaccine development, including future directions to further enhance the relevance of these models to at-risk patient populations.
Topics: Host-Pathogen Interactions; Human Experimentation; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 27889256
DOI: 10.1016/j.vaccine.2016.08.086 -
Communications Biology Jun 2023Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are related RNA viruses responsible for severe respiratory infections and resulting disease in...
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are related RNA viruses responsible for severe respiratory infections and resulting disease in infants, elderly, and immunocompromised adults. Therapeutic small molecule inhibitors that bind to the RSV polymerase and inhibit viral replication are being developed, but their binding sites and molecular mechanisms of action remain largely unknown. Here we report a conserved allosteric inhibitory site identified on the L polymerase proteins of RSV and HMPV that can be targeted by a dual-specificity, non-nucleoside inhibitor, termed MRK-1. Cryo-EM structures of the inhibitor in complexes with truncated RSV and full-length HMPV polymerase proteins provide a structural understanding of how MRK-1 is active against both viruses. Functional analyses indicate that MRK-1 inhibits conformational changes necessary for the polymerase to engage in RNA synthesis initiation and to transition into an elongation mode. Competition studies reveal that the MRK-1 binding pocket is distinct from that of a capping inhibitor with an overlapping resistance profile, suggesting that the polymerase conformation bound by MRK-1 may be distinct from that involved in mRNA capping. These findings should facilitate optimization of dual RSV and HMPV replication inhibitors and provide insights into the molecular mechanisms underlying their polymerase activities.
Topics: Infant; Adult; Humans; Aged; Metapneumovirus; RNA-Dependent RNA Polymerase; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; RNA, Messenger
PubMed: 37337079
DOI: 10.1038/s42003-023-04990-0 -
The Journal of Pediatrics Dec 2021
Topics: Brain; Humans; Influenza, Human; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34450121
DOI: 10.1016/j.jpeds.2021.08.037 -
Current Topics in Microbiology and... 2018Analysis of host gene expression profiles following viral infections of target cells/tissues can reveal crucial insights into the host: virus interaction and enables the... (Review)
Review
Analysis of host gene expression profiles following viral infections of target cells/tissues can reveal crucial insights into the host: virus interaction and enables the development of novel therapeutics and prophylactics. Regions of the host genome that do not code for protein, encode structural, and functional non-coding RNAs that are important not only in regulation of host gene expression but also may impact viral replication. This review summarizes the role of host non-coding RNAs during replication of multiple respiratory viruses with a focus on Respiratory Syncytial Virus (RSV), an important pediatric pathogen. This review highlights the current state of knowledge and understanding regarding the function(s) of ncRNAs for respiratory viral infection and host immunity in general.
Topics: Host-Pathogen Interactions; Humans; RNA, Untranslated; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Virus Replication
PubMed: 28646339
DOI: 10.1007/82_2017_32 -
The Lancet. Digital Health Nov 2023
Topics: Humans; Infant; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 37890899
DOI: 10.1016/S2589-7500(23)00206-6 -
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 -
Clinical Infectious Diseases : An... Jun 2021
Topics: Child; Child, Preschool; Communicable Diseases; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Severity of Illness Index
PubMed: 33216146
DOI: 10.1093/cid/ciaa1753 -
The Journal of Pediatrics Jan 2021
Topics: Antibodies, Monoclonal, Humanized; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 33342497
DOI: 10.1016/j.jpeds.2020.10.066