Human Metapneumovirus: lessons learned over the first decade

Abstract

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.

Fig. 1.

Electron micrograph of HMPV particles. Virions concentrated from infected cell culture supernatants were visualized by negative-contrast electron microscopy after phosphotungstic acid staining. Magnification, ×92,000.

Fig. 2.

Genomic maps of HMPV and RSV showing the important differences between the two viruses. Compared to HMPV, RSV expresses two extra proteins, NS1 and NS2, the positions of the SH and G proteins differ, and the reading frames for M2 and L overlap in RSV. The double diagonal lines crossing the L ORF indicate the shortened representation of the L gene. Le, leader; N, nucleoprotein; P, phosphoprotein; M, matrix protein; F, fusion protein; SH, small hydrophobic protein; G, attachment protein; L, large polymerase protein; Tr, trailer; NS1 and NS2, nonstructural proteins 1 and 2.

Fig. 3.

Schematic representation of the HMPV life cycle. After attachment of the virion to the plasma membrane, the viral and plasma membranes fuse, resulting in uncoating of the virion and release of the RNP (containing the negative-sense viral RNA) into the cytoplasm. After primary transcription, the genome is replicated to produce the antigenome. The antigenome is used to synthesize genomic RNA, which is used to produce additional antigenomes for incorporation into progeny virions or as a template for secondary transcription. After translation, M proteins and RNPs are transported intracellularly to the plasma membrane and the viral glycoproteins F (fusion), G (glycoprotein), and SH (small hydrophobic) are transported from the endoplasmic reticulum (ER) to the Golgi apparatus and then the plasma membrane. Finally, new virions are assembled and are subsequently released from the plasma membrane by a budding process.

Fig. 4.

Phylogenetic trees for fusion (F) and attachment (G) genes of selected HMPV isolates. For each of the four genetic lineages (233), four representative isolates were selected, and maximum likelihood trees were generated for the G gene (right) and for 451 nucleotides of the F gene (left). Numbers in trees represent percent amino acid identities between virus isolates.