Human metapneumovirus

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Human metapneumovirus (HMPV) is a negative-sense 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 by using the RAP-PCR (RNA arbitrarily primed PCR) technique for identification of unknown viruses growing in cultured cells. It is the second most common cause after human respiratory syncytial virus (RSV) of lower respiratory infection in young children.

The peak age of hospitalization for infants with HMPV occurs between 6-12 months of age, slightly older than the peak of RSV, which is around 2-3 months. The clinical features and severity of HMPV are similar to those of RSV. HMPV is also an important cause of disease in older adults.

Video Human metapneumovirus

Taxonomy

Table legend: "*" denotes type species.

Maps Human metapneumovirus

Epidemiology

HMPV is associated with 6% to 40% of respiratory tract infections in hospitalized and outpatient children. The virus is distributed worldwide and, in temperate regions, has a seasonal distribution generally following that of RSV and influenza virus during late winter and spring. Serologic studies have shown that by the age of five, virtually all children worldwide have been exposed to the virus. Despite near universal infection during early life, reinfections are common in older children and adults. Human metapneumovirus may cause mild upper respiratory tract infection (the common cold). However, premature infants, immunocompromised persons, and older adults >65 years are at risk for severe disease and hospitalization. In some studies of hospitalizations and emergency room visits, HMPV is nearly as common and as severe as influenza in older adults. HMPV is associated with more severe disease in people with asthma and adults with chronic obstructive pulmonary disease (COPD). Numerous outbreaks of HMPV have been reported in long-term care facilities for children and adults, causing fatalities.

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Genome

The genomic organisation of HMPV is similar to RSV; 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.

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Virology

HMPV infects airway epithelial cells in the nose and lung. HMPV is thought to attach to the target cell via the glycoprotein (G) protein interactions with heparan sulfate and other glycosaminoglycans. The HMPV fusion (F) protein encodes an RGD (Arg-Gly-Asp) motif that engages RGD-binding integrins as cellular receptors, then mediates fusion of the cell membrane and viral envelope in a pH-independent fashion, likely within endosomes.

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Detection

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.

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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.

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Treatment

No treatment is yet known, but ribavirin has shown effectiveness in an animal model.

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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).

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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.

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References

External links

• ICTV Online (10th) Report Pneumoviridae
• hMPV EIA kit
• hMPV, Human Metapnuemovirus
• Virus Pathogen Database and Analysis Resource (ViPR): Paramyxoviridae

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