Rubella virus: Classification, structure, resistance and replication

86

The History of Rubella Virus Discovery

Rubella virus (RV) is the causative agent of the same name rubella disease. The earliest description of rubella goes back to the 1700s, when the clinical manifestations of this illness were described by two German physicians, de Bergan in 1752 and Orlow in 1758. At this time it was considered to be a derivative of measles, thus the disease became known as German measles. The illness was renamed “rubella” (Lat. – reddish) in 1866 by H. Veale.

Y. Hiro and S. Tasaka in 1938 established the viral etiology of the disease. In 1941 N. Gregg reported the devastating teratogenic effects of the virus. And finally, the isolation of rubella virus culture was elaborated by P.D. Parkman and T.H. Weller with F.A. Neva in 1962.

Classification of Virus

Rubella virus is placed into Togaviridae family. It is classified as the single species of the genus Rubivirus.

Humans are the only known natural hosts for RV.

Structure of Rubella Virus

Rubella virion is a spherical particle about 60 nm in diameter. Virion envelope is composed of host-derived lipid bilayer with embedded spikes made up of E1 and E2 glycoproteins.

Icosahedral internal capsid, or core, made of C proteins holds viral genome. Genome is composed of non-segmented single-stranded RNA of positive polarity.

Viral genome encodes several enzymes, including replicase (RNA-dependent RNA polymerase), protease and helicase.

Virus possesses core protein antigen and surface external glycoprotein antigens E1 and E2, which develop hemagglutinating activity and can cause the synthesis of neutralizing antibodies. Only one serotype of virus exists.

Virion Resistance

The viability of rubella viruses beyond the human body is rather low. They stay infectious outside only for about 1 day. These viruses gradually lose infectivity under freezing; heating at 50-56oC kills them in 5-20 minutes. They are readily inactivated by ether, organic solvents, disinfectants and UV light. Also they are sensitive to pH fluctuations losing the stability at pH levels less than 6.8 and above 8.0. Viral Replication Cycle

RV enters susceptible cells via endosomal uptake. Viral E1 and E2 glycoproteins under endosome acidification stimulate the fusion of the viral envelope to the endosomal membrane. Uncoating occurs within the endosome, allowing next release of viral genomic RNA. Low pH of the endosome promotes not only virion envelope fusion but also triggers uncoating of the capsid protein.

Virus-modified cytoplasmic endosome-lysosomal structures (termed as replication complexes) are the sites of RV replication.

Viral genomic (+) RNA is translated on ribosomes creating early viral proteins (i.e., enzymes replicase, protease and helicase). Initially single polyprotein chain is formed that is further processed into final proteins by proteases.

Replicase enzyme catalyzes the synthesis of genomic positive RNA through the stage of double-stranded RNA intermediate, containing both positive and negative RNA strands. Positive RNAs serve as templates for next synthesis of non-structural and capsid viral proteins.

Replication complexes contain small vesicles, where viral morphogenesis takes place.

After assembly virus is released out of the cell by budding. It is not followed by cell lysis.

Overall, the duration of replication cycle of rubella virus is long and covers 36-46 hours.