Human metapneumovirus (HMPV) is an enveloped, negative-sense, single-stranded RNA virus belonging to the family Pneumoviridae, which also contains respiratory syncytial virus (RSV). HMPV was first identified in 2001 in the Netherlands, although retrospective studies indicate it has circulated in the human population for decades prior to its discovery. It is now recognised as one of the leading causes of acute respiratory tract infection worldwide, alongside RSV and influenza.

HMPV enters host cells through attachment of the viral fusion (F) glycoprotein to cell-surface integrins and glycosaminoglycans, followed by direct fusion of the viral envelope with the plasma membrane, a process that, unlike many respiratory viruses, does not strictly require receptor-mediated endocytosis, although endocytic entry pathways have also been described. Following fusion, the viral ribonucleoprotein complex is released into the cytoplasm, where the viral RNA-dependent RNA polymerase carries out both transcription and replication of the genome. Newly assembled virions bud from the plasma membrane at sites where viral proteins accumulate in lipid-raft-like microdomains.

The HMPV genome is non-segmented and comprises eight genes encoding nine proteins, including three surface glycoproteins, fusion (F), attachment (G), and small hydrophobic (SH). The F protein mediates membrane fusion, is highly conserved between strains, and is the principal target of neutralising antibodies, while the G protein is more variable and contributes to immune evasion. HMPV strains are classified into two major genetic groups, A and B, each further divided into subgroups, and continued antigenic and genetic diversification allows the virus to cause repeated infections throughout life despite prior exposure.

HMPV is transmitted through respiratory droplets and direct or indirect contact with contaminated secretions or surfaces. Infection causes a spectrum of respiratory illness ranging from mild upper respiratory symptoms, such as cough, fever, and nasal congestion, to more severe lower respiratory tract disease, including bronchiolitis and pneumonia. Nearly all children have been infected by HMPV by the age of five, and reinfections are common across the lifespan. Severe disease and hospitalisation occur most frequently in young infants, older adults, and people with weakened immune systems or underlying cardiopulmonary conditions.

HMPV circulates seasonally, typically peaking in late winter and spring in temperate regions and often overlapping with RSV and influenza activity, which complicates clinical differentiation between these pathogens. Globally, HMPV is estimated to be associated with tens of millions of cases of acute lower respiratory infection in young children each year, along with substantial hospitalisation and mortality, particularly in infants and immunocompromised populations. Broader use of molecular diagnostic testing in recent years has increased recognition of HMPV as a significant contributor to the overall burden of respiratory disease.

There is currently no licensed antiviral therapy or vaccine specifically approved for HMPV, and clinical management remains supportive, centred on hydration, rest, and, in more severe cases, oxygen therapy and respiratory support. A number of vaccine candidates, including mRNA, subunit, live-attenuated, and vector-based platforms, together with monoclonal antibodies targeting the F protein, are in preclinical and early clinical development, with some showing promising immunogenicity in trials. Repurposed antiviral compounds such as ribavirin have also been investigated, although with limited clinical evidence to date. Prevention therefore continues to rely on general respiratory hygiene measures, including hand washing, surface cleaning, and staying home when symptomatic.

Overall, human metapneumovirus is an important and likely under-recognised cause of respiratory illness across all age groups, with a particular impact on infants, older adults, and immunocompromised individuals. The absence of any licensed vaccine or antiviral, combined with its close clinical overlap with RSV and influenza, continues to make HMPV a priority for diagnostic development, surveillance, and vaccine and therapeutic research.