Background

In 2001, a new infectious agent, human metapneumovirus (hMPV), was isolated from nasopharyngeal aspirates of young children with respiratory tract illness from The Netherlands [1]. Initially, hMPV was isolated from children with clinical symptoms of respiratory syncytial virus (RSV) infec tion in whom RSV could not be detected. Since then, numerous reports have described the detection of hMPV in clinical specimens from children, adults and the elderly (both immunocompetent and immunocompromised patients), diagnosed with an acute respiratory tract infection (RTI) all over the world.

hMPV is an enveloped virus with a genome that is a single strand of RNA of approximately 13 kb [1]. Its genome contains eight genes that presumably code for nine different proteins [2, 3]. The genomic organization for hMPV is similar but not identical to that for RSV being a member of the Pneumovirus. In contrast to the Pneumovirus, the Metapneumovirus lacks the NS1 and NS2 genes and has a different positioning of the other common genes, i.e., the N (nucleocapsid RNA binding protein), P (phosphoprotein), M (matrix protein), F (fusion glycoprotein), L (major polymerase subunit), G (major attachment protein), M2 (transcription elongation and RNA synthesis regulatory factor), and SH (small hydrophobic surface protein). The absence of open reading frames (ORFs) between the M and F genes in the hMPV virus and the lack of NS1 and NS2 genes is in agreement with it being the first identified non-avian member of the Metapneumovirus genus [2, 4]. Genetic analysis of the N, M, P and F genes revealed that hMPV showed a higher sequence homology to the Metapneumovirus genus (average of 66%) as compared to the genus Pneumovirus (average of 30%) [1, 5]. On the basis of the organization of the viral genome and sequence identity to the Metapneumovirus avian pneumovirus, also known as turkey rhinotracheitis virus, hMPV was assigned to be a member of the Metapneumovirus genus of the Paramyxoviridae family. The Metapneumovirus and the Pneumovirus genera are two genera within the subfamily of Pneumovirinae (Fig. 1). The Pneumovirinae and the Paramyxovirinae belong to the Paramyxoviridae family, a group of negatively stranded RNA viruses including several major pathogens of humans and animals. hMPV does not infect chickens or turkeys, and the virus is unlikely to be a zoonotic source.

RT-PCR analyses using primer sets for specific paramyxoviruses (parainfluenza virus, mumps virus, measles virus, RSV, simian virus type 5, Sendai virus and Newcastle disease virus) did not react with the newly identified hMPV, indicating no close genetic relatedness to these viruses. hMPV-spe-cific antisera did not react in immunofluorescence (IF) assays with cells infected with a panel of paramyxoviruses and orthomyxoviruses (parainfluenza viruses, influenza virus A and B, RSV) [1].

Although genetically not closely related, hMPV shares many biological properties with RSV. The hMPV isolates replicate slowly in tertiary monkey kidney (tMK) and rhesus monkey kidney (LLC-MK2) cells, very poorly in Vero cells and A549 cells, and could not be propagated in Madin Darby canine kidney (MDCK) cells or chicken embryo fibroblasts (CEF) [1]. The cytopathic effects are indistinguishable from those caused by RSV, although they occurred slightly later, 10-17 days post inoculation. Electron microscopy revealed paramyxovirus-like pleiomorphic particles of 150-600 nm,

Figure 1. Classification of viral pathogens of the Paramyxoviridae family that infect humans.

with short envelope projections of 13-17 nm, indistinguishable from RSV [1]. hMPV is chloroform sensitive, and replicates optimally in a trypsin -dependent manner, in contrast to RSV, in tMK cells. No hemagglutinating activity with turkey, chicken or guinea pig erythrocytes was displayed. These combined virological data indicate that the hMPV is indeed a member of the Paramyxoviridae family.

The mode of transmission has not been formally studied, but is likely by large particle respiratory secretions and fomites, based on its relatedness to other pneumoviruses. Nosocomial transmission does occur [6] and warrants contact isolation and scrupulous hand washing by health care providers.

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