Paramyxoviruses: Classification, structure, resistance and replication
The History of Discovery of Pathogenic Paramyxoviruses
First representative of Paramyxoviridae family, measles virus, was detected in 1911 by J. Anderson and J. Goldberger. Then in 1934 C. Johnson and E. Goodpasture isolated the causative agent of epidemic parotitis or mumps – mumps virus. And in 1956 R. Chanock discovered first human parainfluenza virus.
Zoonotic Hendra virus was primarily isolated after infection outbreak in Australia in 1994. Similarly, zoonotic Nipah virus was first isolated in 1998-1999 in Malaysia in the village of Nipah. Later both agents were proved to pertain to paramyxoviruses and placed into the same genus. These viruses are highly pathogenic for humans.
Classification of Paramyxoviruses
The family Paramyxoviridae pertain to the order Mononegavirales.
Human pathogenic viruses belong to genera Respirovirus (with pathogenic species human parainfluenza virus 1 and 3), Rubulavirus (species are human parainfluenza viruses 2, 4, 5, and mumps virus), Morbillivirus, containing measles virus species, and genus Henipavirus with highly pathogenic species Hendra virus and Nipah virus.
Structure of Paramyxoviruses
All paramyxoviruses contain linear single-stranded negative-sense non-segmented RNA.
These viruses are covered with the external lipid envelope of spherical shape. The size of virions is rather large (about 150-300 nm). Sometimes viral particles with the diameter of 400-700 nm can be found.
Viral nucleocapsid displays the helical symmetry.
Paramyxoviruses contain nucleocapsid proteins bound to viral RNA. Internal protein L develops RNA polymerase activity.
Three outer proteins are the structural components of the viral envelope. The matrix (M) protein supports envelope structure; other two glycoproteins are localized in the viral external spikes. The larger glycoprotein (HN) reveals both hemagglutinin and neuraminidase activities (in case of the measles virus – H-protein with hemagglutinin activity only). It promotes viral attachment to the susceptible cells. Another glycoprotein F (or fusion protein) provides membrane fusion and displays hemolytic and cytotoxic activities.
The viability of Paramyxoviridae virions is rather low. They generally stay infectious for several hours only. These viruses can withstand low-temperature exposure for some time, but heating, the action of ether, organic solvents, disinfectants and UV light readily inactivate them. Measles virus is the most unstable agent – it is inactivated within 30 min at room temperature; hence, the disinfection is not performed in measles.
Viral Replication Cycle
The replication of paramyxoviruses occurs in the cytoplasm of infected cells.
Their attachment to the host cells is mediated via hemagglutinin glycoprotein. For measles virus CD46 membrane molecule serves as the cell receptor.
Extracellular proteases of tissues cleave viral F protein that triggers its fusion activity. It activates the direct fusion of the viral envelope with the cell membrane without endosome formation. Fusion is possible only at neutral pH of the extracellular environment; acidification inhibits virus penetration.
Then envelope-free nucleocapsids are released into the cytoplasm.
After uncoating viral RNA polymerase catalyzes the formation of mRNAs that encode viral proteins.
In addition, viral polymerase produces the positive-strand RNA intermediate (antigenome) that serves as the template for synthesis of genomic (–) RNA.
Nucleocapsid assembly is performed in the cytoplasm. Maturating virions migrate towards the cell membrane and interact with HN- and F-proteins. M protein promotes mature particle formation, joining the viral envelope with the nucleocapsid. Finally paramyxoviruses are released from the infected cells by budding.
In case of intracellular protease presence, viral F protein is cleaved and activated progressively, resulting in fusion of the host cell membranes with symplast and syncytia formation.
During the replication cycle acidophilic cytoplasmic inclusions appear within the cells. Measles virus can produce intranuclear inclusions.