Project description:The human Metapneumovirus (HMPV), a new member of the Paramyxoviridae family, has been recently associated with respiratory tract infections in young children. We report the case of a young, immunocompromised child who had severe lower respiratory tract infections during two consecutive winter seasons caused by genetically distinct HMPV strains.
Project description:Human metapneumovirus (hMPV) utilizes a bifurcated cellular entry strategy, fusing either with the plasma membrane or, after endocytosis, with the endosome membrane. Whether cellular factors restrict or enhance either entry pathway is largely unknown. We found that the interferon-induced transmembrane protein 3 (IFITM3) inhibits hMPV infection to an extent similar to endocytosis-inhibiting drugs, and an IFITM3 variant that accumulates at the plasma membrane in addition to its endosome localization provided increased virus restriction. Mechanistically, IFITM3 blocks hMPV F protein-mediated membrane fusion, and inhibition of infection was reversed by the membrane destabilizing drug amphotericin B. Conversely, we found that infection by some hMPV strains is enhanced by the endosomal protein toll-like receptor 7 (TLR7), and that IFITM3 retains the ability to restrict hMPV infection even in cells expressing TLR7. Overall, our results identify IFITM3 as an endosomal restriction factor that limits hMPV infection of cells.
Project description:The transmission of human metapneumovirus (hMPV) among family members is not well understood. We identified 15 families in which multiple members were diagnosed with hMPV infection by real-time PCR in 2008 and 2010. Index patients ranged in age from 2 years to 11 years (median 5 years), and all 15 index cases were children who attended primary school, kindergarten, or nursery school. Contact patients ranged in age from 2 months to 46 years (median 6 years). Excluding five adult cases, contact patients were significantly younger than index patients (P = 0·0389). Of the 12 contact children, seven (58%) were infants who were taken care of at home. The serial interval between the onset of symptoms in an index patient and the onset of symptoms in a contact patient was estimated to be 5 days. These results suggest that the control of school-based outbreaks is important for preventing hMPV infection in infants.
Project description:Human metapneumovirus (hMPV) has been recently discovered as an etiological agent of acute respiratory infections. Our purpose was to asses the virological and clinical features of children with respiratory infections caused by hMPV. We examined 658 nasopharyngeal swab samples obtained from 637 children with respiratory infections for hMPV by using reverse transcription-PCR (RT-PCR). A total of 268 samples from 637 children were inoculated onto tertiary monkey kidney cells. A total of 36 serum samples (26 in the acute phase and 10 in the convalescent phase) from the 26 hMPV-positive children were tested for immunoglobulin G (IgG) and IgM antibodies to hMPV by using an indirect immunofluorescence assay. We detected hMPV in 57 (8.9%) of the 637 samples by using RT-PCR and isolated 7 (2.6%) hMPV strains of the 268 samples in cell cultures. A total of 12 (46.2%) of 26 hMPV-positive children were suspected to have primary infection with hMPV as determined by an indirect immunofluorescence assay. The infected children were diagnosed as having wheezy bronchitis (36.8%), upper respiratory tract infection (26.3%), bronchitis (22.8%), and pneumonia (14.0%). We showed that two hMPV groups were circulating in different regions during the same period and that reinfection with hMPV frequently occurs in childhood. The RT-PCR test is the most sensitive test for detection of hMPV, and a serological test may be useful to differentiate between primary infection and reinfection with hMPV.
Project description:Human metapneumovirus (hMPV) is a recently described paramyxovirus that causes lower respiratory infections in children and adults worldwide. The hMPV fusion (F) protein is a membrane-anchored glycoprotein and major protective antigen. All hMPV F protein sequences determined to date contain an Arg-Gly-Asp (RGD) sequence, suggesting that F engages RGD-binding integrins to mediate cell entry. The divalent cation chelator EDTA, which disrupts heterodimeric integrin interactions, inhibits infectivity of hMPV but not the closely related respiratory syncytial virus (RSV), which lacks an RGD motif. Function-blocking antibodies specific for alphavbeta1 integrin inhibit infectivity of hMPV but not RSV. Transfection of nonpermissive cells with alphav or beta1 cDNAs confers hMPV infectivity, whereas reduction of alphav and beta1 integrin expression by siRNA inhibits hMPV infection. Recombinant hMPV F protein binds to cells, whereas Arg-Gly-Glu (RGE)-mutant F protein does not. These data suggest that alphavbeta1 integrin is a functional receptor for hMPV.
Project description:Zoonotic disease transmission and infections are of particular concern for humans and closely related great apes. In 2009, an outbreak of human metapneumovirus infection was associated with the death of a captive chimpanzee in Chicago, Illinois, USA. Biosecurity and surveillance for this virus in captive great ape populations should be considered.
Project description:Human metapneumovirus (hMPV), a newly discovered paramyxovirus, has been associated with acute respiratory tract infections (ARIs) ranging from upper ARIs to severe bronchiolitis and pneumonia. Important questions remain on the contribution of hMPV to ARIs and its impact on public health. During the 2001-2002 season, we conducted a collaborative study with four provincial public health laboratories to study the prevalence of this new virus in the Canadian population. A total of 445 specimens were collected from patients of all age groups with ARIs and were tested for the presence of hMPV by reverse transcription-PCR. Of these, 66 (14.8%) tested positive for hMPV. Positive specimens were found in all age groups and in all four provinces studied. Virus activity peaked in February and March. The age range of the patients with hMPV infection was 2 months to 93 years (median age, 25 years), with similar numbers of females (35%) and males (41%). Thirty-three percent (n = 22) of hMPV-infected patients were hospitalized; of these, 27% (n = 6) had rhinitis and pneumonia, 23% (n = 5) had bronchiolitis, and 9% (n = 2) had bronchitis. The hospitalization rates were significantly higher among patients <5 years of age (P = 0.0005) and those >50 years of age (P = 0.0044) than among those 6 to 50 years of age. Phylogenetic analysis of the F gene showed that two hMPV genetic clusters were cocirculating in the 2001-2002 season, and comparison with earlier studies suggests a temporal evolutionary pattern of hMPV isolates. These results provide further evidence of the importance of hMPV in ARIs, particularly in young children and elderly individuals.
Project description:We report a case of human metapneumovirus infection that spread from humans to chimpanzees and back to humans. Bronchopneumonia developed in 4 of 6 members of a chimpanzee family, and 2 subsequently died. The chimpanzees' keeper also became ill. Sequencing showed 100% identity between virus sequences from chimpanzees and the keeper.
Project description:The genetic relatedness of mountain gorillas and humans has led to concerns about interspecies transmission of infectious agents. Human-to-gorilla transmission may explain human metapneumovirus in 2 wild mountain gorillas that died during a respiratory disease outbreak in Rwanda in 2009. Surveillance is needed to ensure survival of these critically endangered animals.
Project description:BackgroundThe inpatient and outpatient burden of human metapneumovirus (HMPV) infection among young children has not been well established.MethodsWe conducted prospective, population-based surveillance for acute respiratory illness or fever among inpatient and outpatient children less than 5 years of age in three U.S. counties from 2003 through 2009. Clinical and demographic data were obtained from parents and medical records, HMPV was detected by means of a reverse-transcriptase polymerase-chain-reaction assay, and population-based rates of hospitalization and estimated rates of outpatient visits associated with HMPV infection were determined.ResultsHMPV was detected in 200 of 3490 hospitalized children (6%), 222 of 3257 children in outpatient clinics (7%), 224 of 3001 children in the emergency department (7%), and 10 of 770 asymptomatic controls (1%). Overall annual rates of hospitalization associated with HMPV infection were 1 per 1000 children less than 5 years of age, 3 per 1000 infants less than 6 months of age, and 2 per 1000 children 6 to 11 months of age. Children hospitalized with HMPV infection, as compared with those hospitalized without HMPV infection, were older and more likely to receive a diagnosis of pneumonia or asthma, to require supplemental oxygen, and to have a longer stay in the intensive care unit. The estimated annual burden of outpatient visits associated with HMPV infection was 55 clinic visits and 13 emergency department visits per 1000 children. The majority of HMPV-positive inpatient and outpatient children had no underlying medical conditions, although premature birth and asthma were more frequent among hospitalized children with HMPV infection than among those without HMPV infection.ConclusionsHMPV infection is associated with a substantial burden of hospitalizations and outpatient visits among children throughout the first 5 years of life, especially during the first year. Most children with HMPV infection were previously healthy. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health.).