Human metapneumovirus

Human metapneumovirus (HMPV) is a negative single-stranded RNA virus of the family Pneumoviridae and is closely related to the avian metapneumovirus (AMPV) subgroup C. It was isolated for the first time in 2001 in the Netherlands^[1] by using the RAP-PCR (RNA arbitrarily primed PCR) technique for identification of unknown viruses growing in cultured cells. It may be the second most common cause (after the human respiratory syncytial virus) of lower respiratory infection in young children.

Compared with respiratory syncytial virus, infection with human metapneumovirus tends to occur in slightly older children and to produce disease that is less severe. Co-infection with both viruses can occur, and is generally associated with worse disease.

Taxonomy

Table legend: "*" denotes type species.

Epidemiology

Human metapneumovirus accounts for approximately 10% of respiratory tract infections that are not related to previously known etiologic agents. The virus seems to be distributed worldwide and to have a seasonal distribution with its incidence comparable to that for the influenza viruses during winter. Serologic studies have shown that by the age of five, virtually all children have been exposed to the virus and reinfections appear to be common. Human metapneumovirus may cause mild respiratory tract infection. However, small children, elderly and immunocompromised individuals are at risk of severe disease and hospitalization.

Genome

The genomic organisation of HMPV is analogous to HRSV, however HMPV lacks the non-structural genes, NS1 and NS2, and the HMPV antisense RNA genome contains eight open reading frames in slightly different gene order than RSV (viz. 3’-N-P-M-F-M2-SH-G-L-5’). HMPV is genetically similar to the avian metapneumoviruses A, B and in particular type C. Phylogenetic analysis of HMPV has demonstrated the existence of two main genetic lineages termed subtype A and B containing within them the subgroups A1/A2 and B1/B2 respectively.

Identification

The identification of HMPV has predominantly relied on reverse-transcriptase polymerase chain reaction (RT-PCR) technology to amplify directly from RNA extracted from respiratory specimens. Alternative more cost-effective approaches to the detection of HMPV by nucleic acid-based approaches have been employed and these include:

1. detection of hMPV antigens in nasopharyngeal secretions by immunofluorescent-antibody test
2. the use of immunofluorescence staining with monoclonal antibodies to detect HMPV in nasopharyngeal secretions and shell vial cultures
3. immunofluorescence assays for detection of hMPV-specific antibodies
4. the use of polyclonal antibodies and direct isolation in cultured cells.

Transmission

There are no conclusive studies to date, however, it is likely that transmission occurs by contact with contaminated secretions, via droplet, aerosol, or fomite vectors. Hospital acquired infections with human metapneumovirus have been reported.^[3]

Treatment

No treatment is yet known,^[4] but ribavirin has shown effectiveness in an animal model.^[5]

Vaccine Research

A licensed vaccine for humans is still many years distant. The Department of Virology of Erasmus MC, Rotterdam in the Netherlands is working on developing a Metapneumovirus vaccine for humans. Enhancement of the binding of palivizumab to the HRSV F protein resulted in a second-generation monoclonal antibody, motavizumab (Numax, MedImmune Inc.), which is currently under study in phase III clinical trials. For members of the Paramyxovirinae subfamily, very young infants are the main target group for immunization. Since these children have not yet developed a mature immune system, a multidose vaccine strategy may be needed, starting in the first weeks of life. The vaccination efficacy in these children may also be hampered by the presence of maternally derived antibodies, which may provide partial protection to wild-type virus infections but also suppress the primary immune response on immunization. Pneumoviruses replicate entirely in the cytoplasm, and this process begins with adsorption of the virus to the cellular receptor on the host cell, directed by the viral attachment protein, variously called G, H (hemagglutinin) or HN (hemagglutinin-neuraminidase).

Evolution

Human metapneumovirus was first reported in 2001 and avian metapneumovirus in the 1970s. There are at least four lineages of human metapneumovirus—A1, A2, B1 and B2. Avian metapneumovirus has been divided into four subgroups—A, B, C and D. Bayesian estimates suggest that human metapneumovirus emerged 119–133 ago and diverged from avian metapneumovirus around 1800.^[6]

References

External links

• hMPV EIA kit
• hMPV, Human Metapnuemovirus
• Virus Pathogen Database and Analysis Resource (ViPR): Paramyxoviridae