Human Metapneumovirus

Etiology

Human metapneumovirus (HMPV) is a respiratory virus that has emerged as one of the most common causes of serious lower respiratory tract illness in children throughout the world.

Etiology

HMPV is an enveloped, single-stranded, nonsegmented, negative-sense RNA genome of the family Pneumoviridae, which comprises large enveloped negative-sense RNA viruses. This taxon was formerly a subfamily within the Paramyxoviridae, but was reclassified in 2016 as a family with two genera, Metapneumovirus (which includes HMPV) and Orthopneumovirus (which includes respiratory syncytial virus [RSV], see Chapter 287 ). HMPV and the avian pneumoviruses are highly related and are separated into the separate genus Metapneumovirus because the gene order in the nonsegmented genome is slightly altered and because avian pneumoviruses/HMPVs lack the genes for two nonstructural proteins, NS1 and NS2, which are encoded at the 3′ end of RSV genomes. These proteins are thought to counteract host type I interferons. The absence of NS1/NS2 in the metapneumoviruses (compared with RSV) may contribute to an overall slightly reduced pathogenicity relative to wild-type RSV strains.

The HMPV genome encodes nine proteins in the order 3′-N-P-M-F-M2-(orf1 and 2)-SH-G-L-5′. The genome also contains noncoding 3′ leader, 5′ trailer, and intergenic regions, consistent with the organization of most paramyxoviruses, with a viral promoter contained in the 3′ end of the genome. The F (fusion), G (glycosylated), and SH (short hydrophobic) proteins are integral membrane proteins on the surfaces of infected cells and virion particles. The F protein is a classic type I integral membrane viral fusion protein that contains two heptad repeats in the extracellular domain that facilitate membrane fusion. There is a predicted protein cleavage site near a hydrophobic fusion peptide that likely is cleaved by an extracellular protease, activating the F protein for fusion. The predicted attachment (G) protein of HMPV exhibits the basic features of a glycosylated type II mucin-like protein. The HMPV G protein differs from the RSV G protein in that it lacks a cysteine noose structure. This protein may inhibit innate immune responses. The internal proteins of the virus appear similar in function to those of other paramyxoviruses.

Epidemiology

HMPV outbreaks occur in annual epidemics during late winter and early spring in temperate climates, often overlapping with the second half of the annual RSV epidemic ( Fig. 288.1 ). Sporadic infections occur year round. The usual period of viral shedding is likely to be many days or even several weeks after primary infection in infants. The incubation period is approximately 3-5 days. Humans are the only source of virus; there is no known animal or environmental reservoir. Transmission occurs by close or direct contact with contaminated secretions involving large-particle aerosols, droplets, or contaminated surfaces. Nosocomial infections have been reported, and contact isolation with excellent handwashing for healthcare providers is critical in medical settings. This virus also affects the elderly, immunocompromised patients, and patients with reactive airways disease more severely than otherwise healthy individuals.

Pathology

Infection is usually limited to the superficial layer of airway epithelial cells and is associated with a local inflammatory infiltrate consisting of lymphocytes and macrophages. Immunocompromised individuals have evidence of both acute and organizing injuries during prolonged infection.