Pneumoviridae

Pneumoviridae (from Greek pneumo-, lung, -viridae, virus from Latin, poison, slimy liquid)^[1][2] is a new virus family in the order Mononegavirales.^[3] It was created in 2016 by elevating the now dissolved paramyxoviral subfamily Pneumovirinae.^[4] Natural hosts include humans, cattle, and rodents.^[5] There are currently 5 species in the Pneumoviridae family, divided between 2 genera (Metapneumovirus and Orthopneumovirus).^[3] Pneumoviruses are pleomorphic, capable of producing spherical and filamentous enveloped virions (virus particles) that vary in size from 150 to 200 nm in diameter. The nucleocapsid consisting of a protein shell and viral nucleic acids has a helical symmetry. Nucleocapsids have a diameter of 13.5 nm and a helical pitch of 6.5 nm.^[6] The genome is composed of negative-sense single-stranded RNA that is non-segmented. It is about 15kb in size, and encodes 11 proteins.^[5] A unique feature of the genome is the M2 gene, which encodes proteins M2-1 and M2-2. The Pneumoviridae M2-1 protein is distinctive, and no homologue has been found in any other virus families. It functions as a processivity factor for the virus RNA-dependent RNA polymerase, and promotes viral RNA synthesis.^[7] Viruses in this family are often associated with respiratory infections, and are transmitted through respiratory secretions.^[5]

Taxonomy

Table legend: "*" denotes type species.

Human metapneumovirus

Human metapneumovirus was first classified as a pneumovirus in 2001. Human metapnuemovirus (HMPV) is a negative single-stranded RNA virus that is the second most common cause of lower respiratory infection in young children. Pneumovirus is intermediate in size between other Paramyxoviridae and the Orthomyxoviridae. Cytoplasmic inclusions are considerably more dense than those of other viruses in the family. Human metapneumovirus is very similar to your common cold; it is an upper respiratory infection. It will typically occur in the winter and early spring. This specific infection is most common in children, especially under the age of five. Common symptoms include runny nose, congestion, sore throat, cough, headache, and fever, which can be seen as a cold. It will typically go away after a few days. If this is seen in people over 75 then there is a cause for concern as it can turn to pneumonia.^{[9][10][11][12][13]}

Life cycle

Pneumoviruses replicate in the cytoplasm of the host cell.^[3][5] First, the virus binds to HN glycoprotein receptors expressed on the surface of the cell.^[5] Then, through the action of the fusion protein, the virus fuses to the host plasma membrane and the nucleocapsid is released.^[5] Prior to undergoing replication, mRNA is transcribed and viral proteins are translated. Transcription is dependent on virally encoded RNA-dependent-RNA-polymerase, which binds the genome at the 3' leader region and then sequentially transcribes each gene. Translation of viral proteins is carried out by host cell ribosomes.^[14][15] Once sufficient P, N, L, and M2 proteins are available to create a capsid around the newly replicated genome, the virus undergoes replication.^[15] After replication, the P, L, and M proteins participate in forming the ribonucleocapsid. Once virion assembly is complete, the virion egresses by budding out of the cell.^[15]

Proteins

N- Nucleocapsid protein. Essential for viral replication and transcription. Plays a major role in forming a capsid around the viral genome.^[16]

P- Phosphoprotein required for replication.^[16] Facilitates RNA-dependent RNA polymerase attachment and recruits M2 protein.^[17]

M1- Matrix protein. Facilitates nucleocapsid and envelope interactions.^[18]

M2-1- Matrix protein. Intragenic and intergenic transcription factor required for mRNA transcript elongation.^[16] Binds to nascent and provides stability in order to prevent premature termination.^[19]

M2-2- Matrix protein. Involved in regulating transcription and replication. When overexpressed, has been shown to inhibit viral replication.^[20]

F- Fusion protein. Type I glycoprotein that facilitates fusion between the virus and the host cell membrane.^[21]

SH- Small hydrophobic protein. Non essential. Exact function is unknown. Suggested to alter membrane permeability and block apoptosis.^[21][22]

G- Type II glycoprotein.^[21] Facilitates virus attachment through interactions with glycosaminoglycans.^[23]

L- RNA dependent RNA polymerase.^[24] Required for replication.^[16] Adds a methylated guanosine cap and poly(A) tail to nascent mRNA.^[24]

References