Human metapneumovirus and respiratory syncytial virus, Brazil

We describe the epidemiologic and clinical characteristics of 111 children attending clinics and hospitals in Aracaju, northeast Brazil, with acute respiratory infections attributable to human metapneumovirus (HMPV), respiratory syncytial virus (RSV), or both in May and June 2002. Fifty-three (48%) children were infected with RSV alone, 19 (17%) with HMPV alone, and 8 (7%) had RSV/HMPV co-infections.     

Human metapneumovirus detection in patients with severe acute respiratory syndrome

We used a combination approach of conventional virus isolation and molecular techniques to detect human metapneumovirus (HMPV) in patients with severe acute respiratory syndrome (SARS). Of the 48 study patients, 25 (52.1%) were infected with HMPV; 6 of these 25 patients were also infected with coronavirus, and another 5 patients (10.4%) were infected with coronavirus alone. Using this combination approach, we found that human laryngeal carcinoma (HEp-2) cells were superior to rhesus monkey kidney (LLC-MK2) cells commonly used in previous studies for isolation of HMPV. These widely available HEp-2 cells should be included in conjunction with a molecular method for cell culture followup to detect HMPV, particularly in patients with SARS.     

Genetic variability of human metapneumovirus amongst an all ages population in Cambodia between 2007 and 2009

First identified in 2001, human metapneumovirus (HMPV) is a novel pathogen and causative agent of acute respiratory tract infection. Re-infection with HMPV is common, and currently there is no available vaccine against HMPV infection. Two genotypes of HMPV have been identified, A and B, both of which can be divided further into at least two distinct sub-genotypes. Here we report the results of the first study to investigate the genetic variability of HMPV strains circulating within Cambodia. The overall incidence of HMPV infection amongst an all-ages population of patients hospitalised with ALRI in Cambodia during 3 consecutive years, between 2007 and 2009, was 1.7%. The incidence of HMPV infection was highest amongst children less than 5 years of age, with pneumonia or bronchopneumonia the most frequent clinical diagnoses across all age groups. The incidence of HMPV infection varied annually. As anticipated, genetic diversity was low amongst the conserved F gene sequences but very high amongst G gene sequences, some strains sharing as little as 56.3% and 34.2% homology at the nucleotide and amino acid levels, respectively. Simultaneous co-circulation of strains belonging to the HMPV sub-genotypes B1, B2 and lineage A2b, amongst patients recruited at 2 geographically distinct provincial hospitals, was detected. Sub-genotype B2 strains were responsible for the majority of the infections detected, and a significant (p  =  0.013) association between infection with lineage A2b strains and disease severity was observed.     

Human metapneumovirus infections in hospitalized children

We evaluated the percentage of hospitalizations for acute respiratory tract infections in children < or =3 years of age attributable to human metapneumovirus (HMPV) and other respiratory viruses in a prospective study during winter and spring 2002. We used real-time polymerase chain assays and other conventional diagnostic methods to detect HMPV, human respiratory syncytial virus (HRSV), and influenza viruses in nasopharyngeal aspirates of children. HMPV was detected in 12 (6%) of the 208 children hospitalized for acute respiratory tract infections, HRSV in 118 (57%), and influenza A in 49 (24%). Bronchiolitis was diagnosed in 8 (68%) and pneumonitis in 2 (17%) of HMPV-infected children; of those with HRSV infection, bronchiolitiss was diagnosed in 99 (84%) and pneumonitis in 30 (25%). None of the HMPV-infected children was admitted to an intensive-care unit, whereas 15% of those with HRSV or influenza A infections were admitted. HMPV is an important cause of illness in young children with a similar, although less severe, clinical presentation to that of HRSV.     

Emerging Human Metapneumovirus Gene Duplication Variants in Patients with Severe Acute Respiratory Infection,China, 2017–2019

We detected human metapneumovirus (HMPV) in 72 (7.1%) of 1,021 patients hospitalized with severe acute respiratory infection in Luohe, China, during 2017–2019. We detected HMPV most frequently in young children and less often in adults. HMPV genotype A2c variants 111 nt and 180 nt duplications predominated, demonstrating their continuing geographic spread.     

Human metapneumovirus in children, Singapore

Four hundred specimens were collected from pediatric patients hospitalized in Singapore; 21 of these specimens tested positive for human metapneumovirus (HMPV), with the A2 genotype predominating. A 5% infection rate was estimated, suggesting that HMPV is a significant cause of morbidity among the pediatric population of Singapore.     

Hospitalization rates for human metapneumovirus infection among 0- to 3-year-olds in Gipuzkoa (Basque Country), Spain

Numerous studies have been published on human metapneumovirus (HMPV) infection, but few have been population based. The main aim of this study was to estimate the incidence rate of hospitalization for community-acquired HMPV infection in infants and children aged <3 years. Between July 2004 and June 2007, 796 episodes (742 patients) of community-acquired acute respiratory infection were hospitalized. HMPV was detected in 90 episodes (11.3%). Fifty-nine episodes occurred in infants aged <1 year. The mean length of hospital stay was 6.2 days (range 2-31 days). Thirteen children required admission to the intensive care unit. Viral co-infections were detected in 46 episodes (51.1%). The incidence rate of hospitalization per 1000 inhabitants was 2.6 (95% CI 2.1-3.2), lower than that for respiratory syncytial virus, but higher than that observed for the influenza and parainfluenza viruses. HMPV is a major respiratory pathogen that leads to a high hospitalization rate.     

Human metapneumovirus, Peru

We retrospectively studied 420 pharyngeal swab specimens collected from Peruvian and Argentinean patients with influenzalike illness in 2002 and 2003 for evidence of human metapneumovirus (HMPV). Twelve specimens (2.3%) were positive by multiple assays. Six specimens yielded HMPV isolates. Four of the 6 isolates were of the uncommon B1 genotype.     

Human metapneumovirus and severity of respiratory syncytial virus disease

We screened 23 children with severe respiratory syncytial virus (RSV) disease and 23 children with mild RSV disease for human metapneumovirus (HMPV). Although HMPV was circulating in Connecticut, none of the 46 RSV-infected patients tested positive for HMPV. In our study population, HMPV did not contribute to the severity of RSV disease.     

Virus-like particle vaccine induces cross-protection against human metapneumovirus infections in mice

Human metapneumovirus (HMPV) is a paramyxovirus that causes acute respiratory-tract infections in children and adults worldwide. A safe and effective vaccine could decrease the burden of disease associated with this novel pathogen. We engineered HMPV viral-like particles (HMPV-VLPs) derived from retroviral core particles that mimic the properties of the viral surface of two HMPV viruses of either lineage A or B. These VLPs functionally display F and G HMPV surface glycoproteins. When injected in mice, HMPV-VLPs induce strong humoral immune response against both homologous and heterologous strains. Moreover, the induced neutralizing antibodies prevented mortality upon subsequent infection of the lungs with both homologous and heterologous viruses. Upon challenge, viral titers in the lungs of immunized animals were significantly reduced as compared to those of control animals. In conclusion, a HMPV-VLP vaccine that induces cross-protective immunity in mice is a promising approach to prevent HMPV infections.     

Soluble recombinant human metapneumovirus G protein is immunogenic but not protective

Human metapneumovirus (HMPV) expresses the major surface glycoproteins F and G. We evaluated the protective efficacy of immunization with G. We generated a recombinant form of G ectodomain (GΔTM) that was secreted from mammalian cells and purified by affinity chromatography. We tested the immunogenicity of GΔTM in cotton rats. Animals were immunized with PBS, GΔTM alone or adjuvanted, or were infected once with HMPV, and challenged with live HMPV at 28 days. Animals vaccinated with adjuvanted and non-adjuvanted GΔTM developed high levels of serum antibodies to both recombinant and native G protein; however, vaccinated animals did not develop neutralizing antibodies and were not protected against virus challenge. Unlike the analogous non-fusion glycoproteins of other human paramyxoviruses, HMPV G does not appear to be a protective antigen. This represents an unusual feature of HMPV.     

Human metapneumovirus RNA in encephalitis patient

We describe a fatal case of encephalitis that might be correlated with primary human metapneumovirus (HMPV) encephalitis. Postmortem HMPV RNA was detected in brain and lung tissue samples from the patient. Furthermore, HMPV RNA was found in culture fluids from cells coincubated with lung tissue.     

Antigenic and genetic variability of human metapneumoviruses

Human metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups on the basis of genetic or antigenic differences or both. For HMPV, the existence of different genetic lineages has been described on the basis of variation in a limited set of available sequences. We address the antigenic relationship between genetic lineages in virus neutralization assays. In addition, we analyzed the genetic diversity of HMPV by phylogenetic analysis of sequences obtained for part of the fusion protein (n = 84) and the complete attachment protein open reading frames (n = 35). On the basis of sequence diversity between attachment protein genes and the differences in virus neutralization titers, two HMPV serotypes were defined. Each serotype could be divided into two genetic lineages, but these did not reflect major antigenic differences.     

Respiratory tract reinfections by the new human Metapneumovirus in an immunocompromised child

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.     

Human metapneumovirus infection among children, Bangladesh

We confirmed circulation of human metapneumovirus (HMPV) among children with febrile and respiratory illness in an urban slum in Dhaka, Bangladesh, during active surveillance in 2001. HMPV was the most common single virus identified among febrile children and appears to contribute to the high rates of illness in this population.     

Novel HLA-A2-restricted human metapneumovirus epitopes reduce viral titers in mice and are recognized by human T cells

Human metapneumovirus (HMPV) is a major cause of morbidity and mortality from acute lower respiratory tract illness, with most individuals seropositive by age five. Despite the presence of neutralizing antibodies, secondary infections are common and can be severe in young, elderly, and immunocompromised persons. Preclinical vaccine studies for HMPV have suggested a need for a balanced antibody and T cell immune response to enhance protection and avoid lung immunopathology. We infected transgenic mice expressing human HLA-A*0201 with HMPV and used ELISPOT to screen overlapping and predicted epitope peptides. We identified six novel HLA-A2 restricted CD8⁺ T cell (T_CD8) epitopes, with M_39–47 (M39) immunodominant. Tetramer staining detected M39-specific T_CD8 in lungs and spleen of HMPV-immune mice. Immunization with adjuvant-formulated M39 peptide reduced lung virus titers upon challenge. Finally, we show that T_CD8 from HLA-A*0201 positive humans recognize M39 by IFNγ ELISPOT and tetramer staining. These results will facilitate HMPV vaccine development and human studies.     

Immunogenicity and efficacy of two candidate human metapneumovirus vaccines in cynomolgus macaques

Human metapneumovirus (HMPV) is an important cause of acute respiratory tract disease for which the development of vaccine candidates is warranted. We have previously described the generation of an iscom matrix-adjuvanted HMPV fusion protein subunit vaccine (Fsol) and a live-attenuated vaccine (HMPVM11). Here, we evaluate the immunogenicity and efficacy of these vaccines in cynomolgus macaques. Immunization with Fsol induced HMPV F-specific antibody responses, virus neutralizing antibody titers, and cellular immune responses, but the induced humoral immune response waned rapidly over time. HMPVM11 was strongly attenuated and displayed limited immunogenicity, although immunization with this virus primed for a good secondary HMPV-specific lymphoproliferative response after challenge infection. The duration of virus shedding in HMPVM11-immunized animals was reduced compared to sham-immunized animals. Both vaccines induced HMPV-specific immune responses, but the rapid waning of immunity is a challenging obstacle for vaccine development.