Novel Human Metapneumovirus Sublineage

Huck, Barbara; Scharf, Gesa; Neumann‐Haefelin, Dieter; Puppe, Wolfram; Weigl, Josef; Falcone, Valeria

doi:10.3201/eid1201.050772

Cited by 136 publications

(177 citation statements)

References 15 publications

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“…Our results indicate a 30 to 50% reduction in HMPV entry when intracellular pH is raised, suggesting that the low pH environment of the endosomal pathway can stimulate fusion and entry. The two major subtypes of HMPV, clade A and clade B, both contain multiple strains currently circulating in the human population, with clade A viruses often seen at a more prevalent rate (29). A recent report (27) found differences in the effect of pH on fusion promoted by HMPV F proteins from different strains.…”

Section: Discussionmentioning

confidence: 99%

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Schowalter

Chang

Robach

et al. 2009

J Virol

115

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Human metapneumovirus (HMPV) is a significant respiratory pathogen classified in the Pneumovirinae subfamily of the paramyxovirus family. Recently, we demonstrated that HMPV F protein-promoted cell-cell fusion is stimulated by exposure to low pH, in contrast to what is observed for other paramyxovirus F proteins. In the present study, we examined the potential role of histidine protonation in HMPV F fusion and investigated the role of low pH in HMPV viral entry. Mutagenesis of the three ectodomain histidine residues of the HMPV F protein demonstrated that the mutation of a histidine in the heptad repeat B linker domain (H435) ablated fusion activity without altering cell surface expression or proteolytic processing significantly. Modeling of the HMPV F protein revealed several basic residues surrounding this histidine residue, and the mutation of these residues also reduced fusion activity. These results suggest that electrostatic repulsion in the heptad repeat B linker region may contribute to the triggering of HMPV F. In addition, we examined the effect of inhibitors of endosomal acidification or endocytosis on the entry of a recombinant green fluorescent proteinexpressing HMPV. Interestingly, chemicals that raise the pH of endocytic vesicles resulted in a 30 to 50% decrease in HMPV infection, while the inhibitors of endocytosis reduced infection by as much as 90%. These data suggest that HMPV utilizes an endocytic entry mechanism, in contrast to what has been hypothesized for most paramyxoviruses. In addition, our results indicate that HMPV uses the low pH of the endocytic pathway to enhance infectivity, though the role of low pH likely differs from classically described mechanisms.

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Section: Discussionmentioning

confidence: 99%

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Schowalter

Chang

Robach

et al. 2009

J Virol

115

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“…Unfortunately, the virus could not be isolated in cell culture and was therefore not characterized further, and other groups have not confirmed its detection. However, several other groups have subsequently reported the detection of newly emerging sublineages of lineages A and B (2,9,41,44,70,118,146,242). In some of these studies, the available genetic information was limited to only small fragments of the HMPV genome, potentially giving rise to misclassifications.…”

Section: Molecular Epidemiology and Virus Evolutionmentioning

confidence: 99%

Human Metapneumovirus: Lessons Learned over the First Decade

Schildgen

Hoogen²,

Fouchier³

et al. 2011

Clin Microbiol Rev

181

187

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SUMMARY It has been 10 years since human metapneumovirus (HMPV) was identified as a causative agent of respiratory illness in humans. Since then, numerous studies have contributed to a substantial body of knowledge on many aspects of HMPV. This review summarizes our current knowledge on HMPV, HMPV disease pathogenesis, and disease intervention strategies and identifies a number of areas with key questions to be addressed in the future.

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“…Similar to respiratory syncytial virus (RSV), hMPV strains vary genetically and antigenically and have been classified into two broad groups: group A and group B (4,26), with each group divided into genetic subgroups 1 and 2 (12). More recently, phylogenetic analysis showed a further bipartition of subgroup A2 into two new genetic clusters designated A2a and A2b (3).…”

mentioning

confidence: 99%

Detection and Genetic Diversity of Human Metapneumovirus in Hospitalized Children with Acute Respiratory Infections in Southwest China

Zhang

et al. 2012

J Clin Microbiol

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Novel Human Metapneumovirus Sublineage

Abstract: In a pediatric surveillance network, 287 (5.1%) of 5,580 specimens from patients with acute respiratory infections tested positive for human metapneumovirus (HMPV). Phylogenetic analysis of N- and F-gene sequences of identified HMPV showed that 30% belonged to a novel phylogenetic cluster.

Cited by 136 publications

References 15 publications

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Human Metapneumovirus: Lessons Learned over the First Decade

Detection and Genetic Diversity of Human Metapneumovirus in Hospitalized Children with Acute Respiratory Infections in Southwest China

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