Pneumoviridae

The virus family Pneumoviridae (from Greek pneumo- lung, -viridae- virus, from Latin poison, mucous fluid), formerly subfamily Pneumovirinae of the family Paramyxoviridae, comprises viruses within the order Mononegavirales (negative-stranded RNA viruses). They have been delimited from the subfamily Paramyxovirinae. The Pneumoviridae are a family of negative-strand RNA viruses. Humans, cattle, and rodents serve as natural hosts. Respiratory infections are associated with viruses in this family such as human respiratory syncytial virus.

As of ICTV November 2018, the family is divided as follows:

Genus: Orthopneumovirus (known since 1956; formerly called pneumovirus; worldwide occurrence, formation of syncytia of multinucleated giant cells in cell cultures).

• Species: Human orthopneumovirus (human respiratory syncytial virus, HRSV; occurs in the two most common subtypes A and B and the rarer types S2 and RSS-2; causes respiratory infection, common cold; Stein RT et al. 2017).
• Type: Bovine orthopneumovirus (bovine respiratory syncytial virus, BRSV, infecting cattle).
• Species: Murine orthopneumovirus (infects mice)

Genus: Metapneumovirus (known since 2001)

• Species: Avian metapneumovirus (AMPV - affects birds)
• Species: Human metapneumovirus (HMPV, types A1 to 2, B1 to B2 - respiratory infection, colds, also affects chimpanzees and gorillas)

Structure: Pneumoviruses belong to the group of viruses with negative-stranded RNA genome. They are pleomorphic and can form spherical and filamentous enveloped virions (virus particles) varying in size from 150 to 200 nm in diameter. The nucleocapsid, consisting of a protein coat and viral nucleic acids, has a helical symmetry. Nucleocapsids have a diameter of 13.5 nm and a helical pitch of 6.5 nm.

Genome: The genome consists of negative-sense, single-stranded RNA that is not segmented. The genome is about 15 kbp in size and codes for eleven proteins. A unique feature of the genome is the M2 gene, which encodes the M2-1 and M2-2 proteins. The M2-1 protein of pneumovirus is distinctive. No homologue has been found in other virus families. The M2-1 protein functions as a processivity factor for the RNA-dependent RNA polymerase of the virus and promotes viral RNA synthesis. Viruses of this family are commonly associated with respiratory infections and are transmitted through respiratory secretions.

Proteins: N - Nucleocapsid protein. Essential for viral replication and transcription. Plays an important role in the formation of a capsid around the viral genome.

P - Phosphoprotein required for replication. Facilitates binding of RNA-dependent RNA polymerase and recruits M2 protein.

M1 - Matrix protein. Facilitates interaction between nucleocapsid and envelope.

M2-1 - Matrix protein. Intragenic and intergenic transcription factor required for elongation of the mRNA transcript. Binds to nascent RNA and provides stability to prevent premature termination.

M2-2 - Matrix protein. Participates in the regulation of transcription and replication. When overexpressed, has been shown to inhibit viral replication.

F - Fusion protein. Type I glycoprotein that facilitates fusion between the virus and the host cell membrane.

SH - Small hydrophobic protein. Non-essential. Exact function is unknown. It is thought to alter membrane permeability and block apoptosis.

G - Type II glycoprotein. Facilitates viral attachment through interactions with glycosaminoglycans.

L - RNA-dependent RNA polymerase. Required for replication. Adds a methylated guanosine cap and poly(A) tail to nascent mRNA.

Replication: Pneumoviruses replicate in the cytoplasm of the host cell. First, the virus binds to HN glycoprotein receptors expressed on the cell surface. Then, through the action of the fusion protein, the virus fuses with the host plasma membrane and the nucleocapsid is released. Prior to replication, the mRNA is transcribed and viral proteins are translated. Transcription is dependent on the virally encoded RNA-dependent RNA polymerase, which binds the genome at the 3'-leader region and then sequentially transcribes the individual genes. The viral proteins are translated by host cell ribosomes. Once sufficient P, N, L and M2 proteins are available to form a capsid around the newly replicated genome, replication of the virus occurs. After replication, the P, L and M proteins are involved in the formation of the ribonucleocapsid. Once the assembly of the virion is complete, the virion emerges from the cell by budding.

Human metapneumovirus (HMPV) was first classified as a pneumovirus in 2001. It is a negative-strand RNA virus, and the second most common cause of lower respiratory tract infections in young children. Pneumoviruses are intermediate in size between viruses of the families Paramyxoviridae and Orthomyxoviridae. The cytoplasmic inclusions are much denser than in other viruses of the family. Human metapneumovirus infection is very similar to the common cold; it is an upper respiratory tract infection. It typically occurs in winter and early spring. This specific infection is most common in children, especially those under the age of five. Common symptoms include a runny nose, congestion, sore throat, cough, headache, and fever that can feel like a cold. They typically go away after a few days. When this occurs in people over the age of 75, there is reason to be concerned as it can develop into a threatening pneumonia.

Human orthopneumovirus (human respiratory syncytial virus, HRSV) was first identified in chimpanzees in 1956. It occurs in the two most common subtypes A and B and the rarer types S2 and RSS-2. It causes about ¾ of all colds in infants. The infections proceed in the nasopharyngeal region as harmless rhinitis. Severe forms such as bronchiolitis and pneumonia are possible (Borchers AT et al. 2013; Shi T et al. 2017).

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2. Griffiths C et al (2017) Respiratory syncytial virus: infection, detection, and new options for prevention and treatment. Clin Microbiol Rev 30:277-319.
3. Hogan C et al. (2018) Rapid and simple molecular tests for the detection of respiratory syncytial virus: a review. Expert Rev Mol Diagn 18:617-629.
4. Piedimonte G et al (2015) Respiratory syncytial virus infection and bronchiolitis. Pediatr Rev 35:519-530.
5. Shi T et al. (2017) RSV Global Epidemiology Network. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 390:946-958.
6. Stein RT et al. (2017) Respiratory syncytial virus hospitalization and mortality: systematic review and meta-analysis. Pediatr Pulmonol 52:556-569.