Pneumoviridae


Pneumoviridae is a family of Negative-strand [RNA virus|negative-strand RNA viruses] in the order Mononegavirales. Humans, cattle, and rodents serve as natural hosts. Respiratory tract infections are associated with member viruses such as human respiratory syncytial virus. There are five species in the family which are divided between the genera Metapneumovirus and Orthopneumovirus. The family used to be considered as a sub-family of Paramyxoviridae, but has been reclassified as of 2016.

Virology

Structure

Pneumoviruses are pleomorphic, capable of producing spherical and filamentous, enveloped virions 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.

Genome

The genome is composed of negative-sense, single-stranded RNA that is non-segmented. It is about 15 kbp in size, and encodes eleven proteins. A unique feature of the genome is the M2 gene, which encodes proteins M2-1 and M2-2. The pneumovirus 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. Viruses in this family are often associated with respiratory infections, and are transmitted through respiratory secretions.

Proteins

N – Nucleocapsid protein. Essential for viral replication and transcription. Plays a major role in forming a capsid around the viral genome.
P – Phosphoprotein required for replication. Facilitates RNA-dependent RNA polymerase attachment and recruits M2 protein.
M1 – Matrix protein. Facilitates nucleocapsid and envelope interactions.
M2-1 – Matrix protein. Intragenic and intergenic transcription factor required for mRNA transcript elongation. Binds to nascent and provides stability in order to prevent premature termination.
M2-2 – Matrix protein. Involved in regulating transcription and replication. When over expressed, 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. Suggested to alter membrane permeability and block apoptosis.
G – Type II glycoprotein. Facilitates virus 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 surface of the cell. Then, through the action of the fusion protein, the virus fuses to the host plasma membrane and the nucleocapsid is released. 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. Once sufficient P, N, L, and M2 proteins are available to create a capsid around the newly replicated genome, the virus undergoes replication. 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.

Infection in humans

Human metapneumovirus was first classified as a pneumovirus in 2001. It is a negative-strand RNA virus that is the second most common cause of Lower [respiratory tract infection|lower respiratory infection] in young children. Pneumoviruses are intermediate in size between viruses of the families Paramyxoviridae and Orthomyxoviridae. Cytoplasmic inclusions are considerably more dense than those of other viruses in the family. Human metapneumovirus infection is very similar to the 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.