Human metapneumovirus (HMPV or 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 the identification of unknown viruses growing in cultured cells. As of 2016, it was the second most common cause—after respiratory syncytial virus (RSV)—of acute respiratory tract illness in otherwise-healthy children under the age of 5 in a large US outpatient clinic.

The peak age of hospitalization for infants with HMPV is between 6 and 12 months, slightly older than the peak of RSV, which is around 2 to 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 and infants.

Taxonomy

{| class="sortable wikitable"

|+ Genus Metapneumovirus: species and their viruses

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!Genus

!Species

!Virus (abbreviation)

!NCBI taxonomy ID

|- style="vertical-align:top"

| rowspan="2" | Metapneumovirus

| rowspan="1" | Metapneumovirus avis

| rowspan="1" | avian metapneumovirus (AMPV)

| rowspan="1" | 38525

|- style="vertical-align:top"

| rowspan="1" | Metapneumovirus hominis

| rowspan="1" | human metapneumovirus (HMPV)

| rowspan="1" | 162145

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Discovery and naming

Human metapneumovirus (HMPV) was first discovered in 2001 in the Netherlands by Bernadette G. van den Hoogen and her colleagues. HMPV was first detected in the respiratory secretions of 28 young children in the Netherlands and had initially stood out from other common respiratory viruses because the testing methods van den Hoogen and her colleagues had tried using—immunological assays using virus-specific antibodies and PCR-based methods using virus genome-specific primers—were able to test only for known respiratory viruses and, therefore, were unable to identify the novel virus. The virus is distributed worldwide and, in temperate regions, has a seasonal distribution generally following that of RSV and influenza viruses 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.

HMPV may cause mild upper respiratory tract infection (e.g., 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 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.Symptoms include rhinorrhea, nasal congestion, cough, wheezing and sore throat.

Genome

thumb|Model structure and proteins encoded by Human Metapneumovirus (hMPV). (a) hMPV model structure indicating viral proteins encoded by (b) the viral 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. Genotyping based on sequences of the F and G genes showed that subtype B was associated with increased cough duration and increased general respiratory systems compared to HMPV-A.

Life cycle and reproduction

hMPV is estimated to have a 3–6 day incubation period and is often most active during the later winter and spring seasons in temperate climates, overlapping with the RSV and influenza seasons and possibly allowing for repeated infection.

The first step of the hMPV replication cycle is attachment to the host cell, specifically the epithelial cells of the respiratory tract, using the G protein. then mediates fusion of the cell membrane and viral envelope in a pH-independent fashion, likely within endosomes. HMPV then induces the response of chemokines and cytokines such as IL-6, IFN-alpha, TNF-alpha, IL-2, and macrophage inflammatory proteins, which in turn leads to peribronchiolar and perivascular infiltration and inflammation.

Detection

thumb|Frontal chest radiograph of a 47-year-old with encephalitis-associated human metapneumovirus. Consolidation in the right middle lobe (circle) indicating pneumonia.

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.

Distribution and hosts

Though hMPV was first discovered and identified in 2001, serological studies showed that hMPV, or a close relative of it, had already been circulating for at least 50 years. From this information, it is clear that the virus had not just "jumped" from birds, or some other animal reservoir, to humans shortly before its discovery. Hospital-acquired infections with human metapneumovirus have been reported. HMPV has been shown to circulate during autumn and winter months with alternating predominance of a single subtype each year. Ribavirin, a medication used to treat RSV, showed effectiveness in an animal model.

American pharmaceutical corporation Moderna conducted a clinical trial for a candidate modRNA vaccine against metapneumovirus. As of October 2019, the vaccine candidate had passed through phase I, with reports that the vaccine is well-tolerated at all dose levels at two months, and provokes an immune response which boosts the production of neutralising antibodies.

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 between 1875 and 1889 and diverged from avian metapneumovirus around 1800.

2024–2025 outbreak

The Chinese Center for Disease Control and Prevention published data showing that respiratory infections had risen significantly in the week of 16 to 22 December 2024; human metapneumovirus was linked to 6.2 percent of positive respiratory illness tests and 5.4 percent of respiratory-illness hospitalizations in China, more than COVID-19, rhinovirus, or adenovirus. Kan Biao, the head of the China CDC's National Institute for Communicable Disease Control and Prevention, announced that the rate of HMPV among children ages 14 and under was on the rise in China.

References

  • ICTV Virus Taxonomy Profile: Pneumoviridae (December 2017)
  • hMPV EIA kit (Biotrin, archived 13 February 2007)
  • Human Metapneumovirus, hMPV (Biotrin, archived 11 September 2007)

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