Picornaviruses: Classification, structure, resistance and replication
The History of Picornavirus Discovery
The investigation of picornaviruses has commenced as far back as in 1908-1909, when К. Landsteiner and E. Popper demonstrated the viral nature of poliomyelitis. However, poliomyelitis virus was isolated only in 1949 by J. Enders.
In 1948 G. Dalldorf and G. Sickles discovered a new enterovirus during infection outbreak in the town of Coxsackie (USA); hence, it was designated as Coxsackie virus.
First representatives of the numerous group of ECHO viruses were isolated and studied by M Ramos-Alvarez and A. Sabin in 1953-1956.
Classification of Picornaviruses
Picornaviruses pertain to the same name order Picornavirales and family Picornaviridae. This family comprises more than 30 viral genera. The genera of primary medical relevance are Enterovirus, Parechovirus, and Hepatovirus.
Most of pathogenic human viruses belong to genus Enterovirus. It embraces 12 species – 9 enteroviral species Enterovirus A-J (without I) and 3 rhinoviral species Rhinovirus A, B, C.
By their antigenic variations enteroviruses are additionally divided into serogroups encompassing more than 100 serotypes.
Species Enterovirus A contains serotypes of group A Coxsackieviruses.
Species Enterovirus B includes group B Coxsackieviruses and more than 30 serotypes of ECHO-viruses.
Species Enterovirus C comprises polioviruses of 1, 2, 3 serotypes, and the rest of serotypes of group A Coxsackieviruses.
In addition, Enterovirus A, B, and C species harbor many enteroviral serotypes that are not included into certain viral serogroup.
Rhinovirus A, B, and C species represent more than 150 serotypes.
Parechovirus genus (species – parechoviruses А and В) has 14 serotypes; some of them may affect humans. Hepatovirus genus has single serotype (“serotype 72”).
Besides above mentioned agents, in rare cases the members of other picornaviral genera Cardiovirus and Kobuvirus may cause human pathology.
Finally, the representatives of genus Aphthovirus cause foot-and-mouth disease – severe highly contagious epizootic disorder affecting domestic and wild even-toed ungulates – e.g., cattle, sheep or swine.
Structure and Properties of Picornaviruses
Picornaviruses are single stranded positive-sense RNA-containing naked viruses.
Virus size is very small (28-30 nm). Viral nucleocapsid possesses icosahedral symmetry. It is composed of 60 capsomers. Four structural proteins VP1-VP4 of enteroviruses are folded into capsomer unit. Capsid proteins of many picornaviruses possess hemagglutinin activity.
VP4 is tightly bound to viral RNA. Also viral nucleocapsid has small inner Vpg protein.
Slightly distinct parechovirus capsomers are composed of 3 viral proteins. These proteins develop major antigenic activity of enteroviruses.
Virus culture of polioviruses is performed in various cell lines. They don’t propagate in experimental animals or embryonated eggs.
Coxackieviruses are highly pathogenic for newborn (“suckling”) mice.
Picornaviridae members are highly resistant viruses. They can withstand acidic pH, UV irradiation, long-term drying, etc. Viruses can survive in water for about 100 days, in milk for 90 days, in feces and in sewage for several months.
Enteroviruses are sensitive to chlorine-containing disinfectants. Heating at 56° inactivates them in 30 min.
Viral Replication Cycle
Virus attachment is performed via specific receptors of host cell membrane. Polioviruses interact with their specific membrane receptor CD155, whereas many other enteroviruses and all rhinoviruses bind to intercellular adhesion molecule ICAM-1 (or CD54). Specific binding induces viral conformational change with subsequent viral penetration by endocytosis. Acidification of endosome facilitates viral uncoating and RNA release. All cycle of virus propagation takes place in cytoplasm of infected cells.
Viral uncoating is followed by genomic (+) RNA translation, which results in large single polyprotein synthesis. It is rapidly cleaved into several structural and non-structural proteins, including RNA-dependent RNA polymerase (replicase) and viral protease. Subsequent RNA replication occurs through the stage of negative-sense RNA intermediate, which serves as template for viral genome synthesis.
Viral self-assemblage starts from genomic RNA pack into capsid proteins. After complete maturation the progeny viruses are released from the host cells resulting in cell disintegration and lysis. Picornavirus replication cycle takes about 5-10 hours.