Global genetic diversity of human metapneumovirus fusion gene.
Ontology highlight
ABSTRACT:
SUBMITTER: Boivin G
PROVIDER: S-EPMC3323143 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in children. We examined the diversity and molecular evolution of HMPV using 85 full-length F (fusion) gene sequences collected over a 20-year period.The F gene sequences fell into two major groups, each with two subgroups, which exhibited a mean of 96% identity by predicted amino acid sequences. Amino acid identity within and between subgroups was higher than nucleotide identity, suggesting structural or functional constraints on F protein diversity. There was minimal progressive drift over time, and the genetic lineages were stable over the 20-year period. Several canonical amino acid differences discriminated between major subgroups, and polymorphic variations tended to cluster in discrete regions. The estimated rate of mutation was 7.12 x 10(-4) substitutions/site/year and the estimated time to most recent common HMPV ancestor was 97 years (95% likelihood range 66-194 years). Analysis suggested that HMPV diverged from avian metapneumovirus type C (AMPV-C) 269 years ago (95% likelihood range 106-382 years).HMPV F protein remains conserved over decades. HMPV appears to have diverged from AMPV-C fairly recently.
| S-EPMC2753315 | biostudies-literature
Project description:Complete genes encoding the predicted nucleoprotein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), M2-1protein, M2-2protein, small hydrophobic protein (SH), and attachmentprotein (G) of seven newly isolated human metapneumoviruses (hMPVs) were analyzed and compared with previously published data for hMPV genes. Phylogenetic analysis of the nucleotide sequences indicated that there were two genetic groups, tentatively named groups 1 and 2, similar to the grouping of human respiratory syncytial virus. Although the predicted amino acid sequences of N, P, M, F, and M2 were highly conserved between the two groups (amino acid identities, 96% for N, 85% for P, 97% for M, 94% for F, 95% for M2-1, and 90% for M2-2), the amino acid identities of the SH and G proteins were low (SH, 58%; G, 33%). Furthermore, each group could be subdivided into two subgroups by phylogenetic analysis, tentatively named subgroups 1A and 1B and subgroups 2A and 2B. The predicted amino acid sequences of G within members of each subgroup were highly conserved (amino acid identities, 88% for group 1A, 93% for group 1B, and 96% for group 2B). The G of hMPV is thought to be the major antigenic determinant and to play an important role in the production of neutralizing antibodies. Clarification of the antigenic diversity of G is important for epidemiological analysis and for establishment of strategies to prevent hMPV infection.
| S-EPMC497604 | biostudies-literature
Project description:Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November-April) and correlated with higher relative humidity and number of rainy days (P < 0.05). Phylogenetic analysis of the fusion and attachment genes identified the co-circulation of three known HMPV sub-lineages, A2b and B1 (30.2% each, 26/86) and B2 (20.9%, 18/86), with genotype shift from sub-lineage B1 to A2b observed in 2013. Interestingly, a previously unrecognized sub-lineage of A2 was identified in 18.6% (16/86) of the population. Using a custom script for network construction based on the TN93 pairwise genetic distance, we identified up to nine HMPV transmission clusters circulating as multiple sub-epidemics. Although no apparent major outbreak was observed, the increased frequency of transmission clusters (dyads) during seasonal peaks suggests the potential roles of transmission clusters in driving the spread of HMPV. Our findings provide essential information for therapeutic research, prevention strategies, and disease outbreak monitoring of HMPV.
| S-EPMC4899729 | biostudies-literature
Project description:Human metapneumovirus (HMPV) is a leading cause of respiratory infection that causes upper airway and severe lower respiratory tract infections. HMPV infection is initiated by viral surface glycoproteins that attach to cellular receptors and mediate virus membrane fusion with cellular membranes. Most paramyxoviruses use two viral glycoproteins to facilitate virus entry-an attachment protein and a fusion (F) protein. However, membrane fusion for the human paramyxoviruses in the Pneumovirus subfamily, HMPV and respiratory syncytial virus (hRSV), is unique in that the F protein drives fusion in the absence of a separate viral attachment protein. Thus, pneumovirus F proteins can perform the necessary functions for virus entry, i.e., attachment and fusion. In this review, we discuss recent advances in the understanding of how HMPV F mediates both attachment and fusion. We review the requirements for HMPV viral surface glycoproteins during entry and infection, and review the identification of cellular receptors for HMPV F. We also review our current understanding of how HMPV F mediates fusion, concentrating on structural regions of the protein that appear to be critical for membrane fusion activity. Finally, we illuminate key unanswered questions and suggest how further studies can elucidate how this clinically important paramyxovirus fusion protein may have evolved to initiate infection by a unique mechanism.
| S-EPMC3564117 | biostudies-literature
Project description:Human metapneumovirus (hMPV) has been associated with respiratory illnesses like those caused by human respiratory syncytial virus (HRSV) infection. Similar to other pneumoviruses, genetic diversity has been reported for hMPV. Little information is currently available on the genetic variability of the G glycoprotein (G), which is the most variable gene in RSV and avian pneumovirus. The complete nucleotide sequences of the G open reading frame (ORF) of 24 Canadian hMPV isolates were determined. Phylogenetic analysis showed the existence of two major groups or clusters (1 and 2). All but one of the hMPV isolates that we examined belonged to cluster 1. Additional genetic variability was observed in cluster 1, which separated into two genetic subclusters. Within cluster 1 the nucleotide sequence identity for the G ORF was 74.2 to 100%, and the identity for the predicted amino acid sequence was 61.4 to 100%. The G genes of cluster 1 isolates were more divergent from the cluster 2 isolates, with 45.6 to 50.5% and 34.2 to 37.2% identity levels for the nucleotide and amino acid sequences, respectively. Sequence analysis also revealed changes in stop codon usage, resulting in G proteins of different lengths (217, 219, 228, and 236 residues). Western blot analysis with the use of hMPV-specific polyclonal antisera to each hMPV cluster showed significant antigenic divergence between the G proteins of clusters 1 and 2. These results suggest that the G protein of hMPV is continuously evolving and that the genetic diversity observed for the hMPV genes is reflected in the antigenic variability, similar to HRSV.
| S-EPMC497612 | biostudies-literature
Project description:The molecular epidemiology and genetic diversity of the human metapneumovirus (hMPV) were characterized for a 3-year period (2000-2002) from viruses that were identified in South Africa. Two major genetic groups (A and B) and 2 subgroups (1 and 2) of hMPV were identified, as well as 2-6 possible genotypes within the subgroups. A shift in the predominant group was documented in successive seasons. Whereas the F gene was relatively conserved between subgroups, a high degree of variation was observed in the extracellular domain of the G gene of the virus. The G protein identities between groups A and B were 45.1%-53.1% at the nucleotide level and 22.4%-27.6% at the amino acid level. These results provide evidence for the diversity of both surface glycoproteins of hMPV in Africa, which may be a prerequisite to understanding protective immunity against hMPV.
| S-EPMC3371776 | biostudies-literature
Project description:Human metapneumovirus (HMPV) is an important respiratory pathogen and is divided in two main groups (A and B). HMPV strains with partial duplications (111-nt and 180-nt duplication) of the G gene have been reported in recent years. Since the initial reports, viruses with these characteristics have been reported in several countries. We analyzed all complete HMPV G gene ectodomain sequences available at GenBank to determine if viruses with 111-nt or 180-nt duplication have become the leading HMPV strains worldwide, and to describe their temporal and geographic distribution. We identified 1462 sequences that fulfilled study criteria (764 HMPV A and 698 HMPV B) reported from 37 countries. The most frequent HMPV A genotype was A2b2 (n = 366), and the most frequent B genotype was B2 (n = 374). A total of 84 sequences contained the 111-nt duplication, and 90 sequences contained the 180-nt duplication. Since 2016, viruses with a partial duplication comprise the most frequent HMPV A sequences globally and have displaced other HMPV A viruses in Asia, Europe, and South America; no sequences of viruses with partial duplication have been reported in North America or Africa so far. Continued surveillance of HMPV is required to identify the emergence and spread of epidemiologically relevant variants.
| S-EPMC9146545 | biostudies-literature
Project description:The human metapneumovirus (hMPV) fusion (F) protein is essential for viral entry and is a key target of neutralizing antibodies and vaccine development. The prefusion conformation is thought to be the optimal vaccine antigen, but previously described prefusion F proteins expressed poorly and were not well stabilized. Here, we use structures of hMPV F to guide the design of 42 variants containing stabilizing substitutions. Through combinatorial addition of disulfide bonds, cavity-filling substitutions, and improved electrostatic interactions, we describe a prefusion-stabilized F protein (DS-CavEs2) that expresses at 15 mg/L and has a melting temperature of 71.9 °C. Crystal structures of two prefusion-stabilized hMPV F variants reveal that antigenic surfaces are largely unperturbed. Importantly, immunization of mice with DS-CavEs2 elicits significantly higher neutralizing antibody titers against hMPV A1 and B1 viruses than postfusion F. The improved properties of DS-CavEs2 will advance the development of hMPV vaccines and the isolation of therapeutic antibodies.
| S-EPMC8921277 | biostudies-literature
Project description:The human metapneumovirus (HMPV) fusion protein (F) mediates fusion of the viral envelope and cellular membranes to establish infection. HMPV F from some, but not all, viral strains promotes fusion only after exposure to low pH. Previous studies have identified several key residues involved in low pH triggering, including H435 and a proposed requirement for glycine at position 294. We analyzed the different levels of fusion activity, protein expression and cleavage of three HMPV F proteins not previously examined. Interestingly, low pH-triggered fusion in the absence of G294 was identified in one F protein, while a novel histidine residue (H434) was identified that enhanced low pH promoted fusion in another. The third F protein failed to promote cell-to-cell fusion, suggesting other requirements for F protein triggering. Our results demonstrate HMPV F triggering is more complex than previously described and suggest a more intricate mechanism for fusion protein function and activation.
| S-EPMC6486425 | biostudies-literature
Project description:Human metapneumovirus (hMPV) causes acute respiratory infections in children and adults. It is classified into two major genetic lineages and each lineage into two sublineages. The purpose of the study was to identify and characterize hMPV in children who presented to the All India Institute of Medical Sciences, New Delhi, India with acute respiratory infection from April 2005 to March 2007. By reverse-transcription polymerase chain reaction, hMPV was detected in 21 (3%) of the 662 nasopharyngeal samples from children with acute respiratory infection and in none of the 120 control children. Seven of the 21 (33%) children infected with hMPV required hospital admission for pneumonia or bronchiolitis. Most hMPV detections were during the winter and spring seasons. The majority (67%, 11/21) of children positive for hMPV were within 24 months of age. Phylogenetic analysis of partial F and N gene and the full G gene sequences showed three sub-lineages of hMPV circulated during the study period, B1, B2, and the novel sub-lineage A2b. The circulation pattern of hMPV genotypes varied by season. Comparison of the F and G genes of eight strains revealed incongruencies in lineage assignments, raising the possibility that recombination had occurred. Sequence analysis also revealed the F gene was relatively conserved whereas the G gene was more variable between the A and B lineages. This study demonstrates that hMPV is an important contributor to acute respiratory infection in children in India, resulting in both outpatient visits and hospitalizations.
| S-EPMC4412166 | biostudies-literature