Noroviruses are RNA viruses that tend to cause gastroenteritis in a range of species, including humans. They have been labeled the “perfect pathogen” and “the Ferrari of viruses” because of their ability to evolve rapidly and spread at high rates. The physical symptoms of noroviral illness are commonly vomiting and diarrhea, which is the principle mode of viral shedding. Other symptoms include myalgia, stomach cramps, and headaches.
Noroviruses were first identified in 1972, following the initial 1968 outbreak in Norwalk, Ohio, where the name originates. Originally called “Norwalk-like viruses,” norovirus strains are grouped into the Caliciviridae family. The virus itself has been classified into 40 different strains, which has been further divided into genomic groups, I-V. I, II, and IV are known to be pathogenic in humans, with GII being the most common in massive breakouts. Specific strains are usually named after the location of their outbreak such as GII.4 Sydney or Snow Mountain virus.
The norovirus genome is an approximately 7.5 kb, plus-sense, single stranded RNA that contains 3 Open Read Frames (ORFs). ORF1 constitutes nonstructural protein synthesis, and is cleaved by virus protease 3C into 6 proteins that are used in RNA polymerase and other essential cell functions. ORF2 encodes capsid proteins, along with protruding domains (P1 and P2 and shell S). It is believed that the protruding domain plays a significant role in lethality. These arch-like protruding structural proteins are grouped into what is known as VP1 (viral protein 1), which is the main binding site to histo-blood group antigens HBGA. P1 and P2 sites are crucial for cell interactions and immune recognition, because it protrudes from the surface of the capsid. The protruding groups are also considered extremely variable, especially the P2 region. Variation rates between members of the same genogroup are between 45-61% and within genotypes at a rate of 14-44% (Zheng). This is alarming because of the rate of evolution occurring in areas most common for immune response will make permanent immunization (like polio) unlikely. ORF3 contains a basic protein sequence that codes for a small capsid protein, and is important for VP1 stability and interaction with genome RNA during virion formation. It is contested whether ORF3 or ORF2 is more variable, but there is definite consensus that this segment of the genome displays greater change over time.
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