Rasha Raghei

Biology SF01 Essay

Norovirus: The Perfect Pathogen?

What is Norovirus?
Norovirus is a non-enveloped single-stranded RNA virus of the family caliciviridae known
for causing acute gastroenteritis (inflammation of the stomach and small intestines leading to
vomiting and diarrhoea). Noroviruss first recorded outbreak was in an elementary school, followed
by various recordings mostly being in cruise ships, schools, and hospitals (Cdc.gov, 2016). It is
estimated to be the cause of 50% of all gastroenteritis cases, infecting about 21 million people,
hospitalizing over 70,000, and killing about 800 in the US alone annually (Hall, A. 2012). Norovirus
has five genogroups (GI GV) with several genotypes and strains in each; GI and GII are the
genogroups that affect humans (Princeton University, 2010). The norovirus is dubbed as the perfect
pathogen for several characteristics that make it very efficient in causing disease as well as
maintaining survival, making it difficult to make a vaccine (Hall, A. 2012).

Abilities that Make Norovirus an Effective Virus

Norovirus can be transmitted in several ways, both directly and indirectly. Viral particles can
be spread directly through ingestion of contaminated food or drink, and mouth-to-hand spread of
saliva, or indirectly through aerosolized vomitus or faecal particles. The indirect transmission of
norovirus is remarkable, because a hotel outbreak shows evidence of viral particles on untouched
chandeliers. Another incident of indirect norovirus transmission is when an infected football player
developed acute gastroenteritis on a trip without having direct contact with her teammates, yet they
all developed the infection after eating from a lunch bag that was in a bag that was placed near the
bathroom (Hall, A. 2012).
Having an incubation period of 24-48 hours, being moderately harmful (keeping its hosts
alive), the ability to cause asymptomatic infection (spreading silently), rapid shedding (5 billion viral
particles found in one gram of faeces of asymptomatic patients), low infectious ratio of 18 viral
particles, the ability to withstand freezing temperatures up until 60C, and being constantly evolving
are characteristics that enable the efficient spread of norovirus(Karst, S. 2010). An example of their
evolving is the unique pattern of outbreaks in 2002. Since 1990, GII.4 (genogroup GII genotype 4)
dominated 70-80% of outbreaks, however, in winter; in 2002, a variant strain of the genotype GII.4
appeared and infection rate increased dramatically during spring and summer (around 66%), meaning
the virus gained environmental stability (Lopman, B. et al, 2004).

Effects of Norovirus on the Body

Due to the inability to culture human noroviruses, knowledge of its processes inside the body
are based mostly on observations of infected humans, and experiment on murine norovirus (GV
norovirus) and other viruses of the same family caliciviridae (Karst, S. 2010).
When the norovirus enters the body, it goes to the stomach then small intestines. The small
intestines, specifically in the jejunum, is where viral shedding takes place. The viral particles bind to

Rasha Raghei
Biology SF01 Essay
cells with HBGA (histo-blood group antigen) or epithelial cells in the linings of the small intestines.
Norovirus can also bind to HBGA receptor enteric bacteria which release carbohydrates that enhance
the infection of B cells, restricting antibody synthesis (Jones, M. et al 2014). A correlation was found
between the genogroups and histo-blood groups whether A, B, or O; GI better identified cells with
blood group antigens A and O, and GII better identified cells with blood group antigens A and B
(Singh, B. 2014). Once the virus binds to the receptors, it allows endocytosis and enters the cells. It
then unzips its capsid, releasing its genomic RNA into the cytoplasm. VPg (genome-linked virus
particles) from the RNA is then translated into ORF1 polyprotein that codes for the yield of
replication proteins. DsRNA (double-stranded RNA) genome is made by the ssRNA (+) (positive
single-stranded RNA) genomes; the dsRNA then duplicates itself into ssRNA that also serves as
mRNA (messenger RNA). Subgenomic sections of the mRNA are translated into the capsid and VP2
(viral particles 2), finalizing the duplication process. The cells then lysis (burst) releasing the new set
of viruses (ViralZone, 2016).
The bursting of the cells releases fluid from the cells cytoplasm, which is what causes
vomiting, diarrhoea and stomach cramps. With its short incubation period, however, the virus
finishes shedding in about 1-2 days stopping the symptoms, and thus keeping a healthy host
(Microbewiki.kenyon.edu, 2016).

Treatments for Norovirus

Both viruses are from caliciviridae family and have capsids with diameters sized 38 nm and icosahedral symmetry of
T=3 (Karst, S. 2010)

As mentioned earlier, norovirus is difficult to make a vaccine for. The main reasons are that it
has several genetic variants that are constantly evolving, binds to multiple receptors, and is not
cultivable in a lab due to lack of suitable animal models or tissue culture. Nonetheless, current
studies are using similar VLPs of the same family caliciviridae such as Hawaii virus, Norwalk-like
virus, and Snow Mountain virus. The most recent published report about a norovirus vaccine was
published in March 15 2015. In the study, a vaccine was made from the GI and GII.4 ;50g GI and
50g GII.4 made from Norwalk virus VLP and the arrangement of GII.4 capsid protein sequences
respectively). Unsurprisingly, the vaccine was deemed not so successful with a 26% efficiency in 50

Rasha Raghei
Biology SF01 Essay
ill patients, compared to a 33% efficiency using sterile saline as a placebo on 48 ill patients
(Bernstein, D et al 2015).
The symptoms of norovirus can be treated very easily. First, a symptomatic patient loses
plenty of water in diarrhea and vomit, so must constantly drink fluids to avoid dehydration.
Paracetamol and other fever and pain relievers can be taken to ease abdominal cramps. Adult patients
can have anti-diarrheal and anti-vomiting medication. Patients must also reside to light foods such as
soup, crackers, and bread until their stomach feels stronger, and get enough rest (NHS, 2016).

Conclusion
In conclusion, the norovirus deserves being named the perfect pathogen due to its long
success in keeping its effectiveness, maintaining a large pool of hosts, and escaping the potential of a
vaccine. Nonetheless, how long can the norovirus exceed the human ability to make a vaccine
targeting it? With the advancement of technology and the ability to use VLPs of similar viruses, a
vaccine will probably be made soon, and another pathogen will take noroviruss title as the perfect
pathogen.

Rasha Raghei
Biology SF01 Essay

References:
Bernstein, D et al (2015). Norovirus Vaccine Against Experimental Human GII.4 Virus Illness: A
Challenge Study in Healthy Adults. Journal of Infectious Diseases, 211(6), pp.870-878.
Cdc.gov, (2016). Updated Norovirus Outbreak Management and Disease Prevention Guidelines.
[online] Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6003a1.htm [Accessed 26
Jan. 2016].
Hall, A. (2012). Noroviruses: The Perfect Human Pathogens?. Journal of Infectious Diseases,
205(11), pp.1622-1624.
Jones, M et al (2014). Enteric bacteria promote human and mouse norovirus infection of B cells.
Science, 346(6210), pp.755-759.
Karst, S. (2010) Pathogenesis of Noroviruses, Emerging RNA Viruses. Viruses, 2(3), pp: 748-781
Lopman, B. et al (2004). Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of
new norovirus variant. The Lancet, 363(9410), pp.682-688.
Microbewiki.kenyon.edu, (2016). Norovirus - MicrobeWiki. [online] Available at:
https://microbewiki.kenyon.edu/index.php/Norovirus [Accessed 26 Jan. 2016].
NHS, (2016). Norovirus - NHS Choices. [online] Nhs.uk. Available at:
http://www.nhs.uk/Conditions/Norovirus/Pages/Introduction.aspx [Accessed 25 Jan. 2016].
Princeton University, (2010). Viral shape -shifting: Norovirus Evasion of the Human Immune System.
[online] Available at:
https://eeb.princeton.edu/diseasegroup/JournalClub/Donaldson.et.al.2010.ViralShapeShifting.pdf
[Accessed 20 Jan. 2016].
Singh, B. (2014). Human Noroviruses' Fondness for Histo-Blood Group Antigens. J. Virol., 89(4),
pp.2024-2040.