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Recent Advances in Understanding Norovirus

Literature Review
HLTH 499 Capstone
Rachelle Martinez
March 28, 2021
Noroviruses are the leading cause of acute gastroenteritis around the world, affecting people
of all ages and geographic locations (Bartnicki, 2017). Also, known more locally as the “cruise
ship virus”, the Center for Disease Control (CDC) reported that Norovirus is the leading cause of
disease outbreaks from contaminated food in the US and estimated to infect over 20 million
Americans yearly (2019). Despite how common and prevalent this virus is, to date there is no
direct disease prevention or treatment modalities such as in vaccinations that are available
which can assist in protecting the public’s health (Bartnicki, 2017). However, the development
of such treatments is being tested and studying new critical findings that will further the
research and development and understanding of the norovirus. The goal of this paper is to
summarize the recent advances in understanding norovirus including the past difficulty to
cultivate norovirus, norovirus cell tropism, binding and entry as the virus uptake, norovirus and
the intestinal microbiome and lastly the successful usage of microfluidics in norovirus research.
Historically norovirus has been known as difficult to cultivate in a cell culture and then closely
cultivated in small animal models since only murine norovirus affects mine and human
norovirus affects humans (Gutierrez, 2016). In past years while some viruses could grow well,
norovirus did not both in vivo and in vitro. However, in recent years, norovirus research has
seen a breakthrough with the use of in- vitro culture systems for the human norovirus
(Bartnicki, 2017).
This great deal of groundbreaking research has helped to shed light on understanding the
norovirus better and allowing research teams to move closer to targeting and establishing
preventative care such as antiviral and vaccinations. Largely in part by further understanding
novel aspects of the norovirus biology (Bartnicki, 2017) as well as overcoming technical
difficulties with the disease cultivation. The norovirus tropism or cells that it targets was
understood that focus was previously studied to affect the host’s immune system cells such as
dendritic cells and macrophages and later understood that B- cells as well as the intestinal
epithelial cells that line most of the digestive tract (Kim, 2015). A lab created intestinal
environment was not perfectly replicated until the understanding that the norovirus and its
genetic strains required and thrived in the presence of bile acids, such as those found excreted
into the small intestine by the gallbladder. The bile acid was a key to replicate the exact bodily
environment. After the lab enterocytes were infected with norovirus plus the addition of bile
acids even smaller strains replicated in more numbers than previously observed without bile
acids (Gutierrez, 2016).
Norovirus behaves in the way a categorized virus would behave, essentially overtaking the
host’s mechanics and using it to replicate itself to infect and spread throughout the host’s
system. The attachment receptors for most norovirus are Histo-blood group antigens or
HBGA’s, terminal complex carbohydrates of lipid- or protein-linked glycan chains other cells
(Bartnicki, 2017). Norovirus capsids are also discussed as a proposed role in the pathogenesis of
Recent Advances in Understanding Norovirus
Literature Review
HLTH 499 Capstone
Rachelle Martinez
March 28, 2021
the disease (Kim, 2015). New information has been discovered in murine (mouse) norovirus as
two proteinaceous receptors, this is important as the first discovery of a functional receptor for
any strain of norovirus whether murine, bovine or human. The virology of norovirus also has a
relationship with other microbial inhabitants of the intestinal tract being gut bacteria or
intestinal microbiome. A few gut bacterial players are listed in detail in this article as being
present and could possibly be linked to norovirus and trans- microbial worlds (Karst, 2014).
These bacteria are Helicobacter pylori, Lactobacillus and strains of Enterobacter cloacae, that
are present during infection and may be utilized by norovirus just as the host immune cells due
to the norovirus abilities to utilize the bacteria’s resistant qualities. There is still much research
that will need to be completed but the future is very promising in regards to the further
development and studies of the norovirus.
The final topic of this article relates to a new technical development that is being used to more
precisely screen and analyze and even surpass the use of the traditional biochemical-, genetic-
or molecular- based techniques is called Microfluidics (Bartnicki, 2017). The platform uses
aqueous drops dispersed in oil as picoliter-volume reaction vessels (Bartnicki, 2017). They work
like a tiny computer chip of drop-based precision that can analyze individual virus particles and
assess them with much higher precision (Bartnicki, 2017). Microfluidics have played a large role
and will continue to play a large role in furthering the advancement of research for norovirus.
In closing, norovirus is a very remarkable, microbial, viral disease that to develop a direct
related preventative modality will require the efforts of many skilled scientists and technicians
across scientific fields specifically virology, immunology and bacteriology fields to bring even
further understanding and in hopes a preventative care and cure.
References
Bartnicki E, Cunha JB, Kolawole AO, Wobus CE, “Recent Advances in Understanding
Norovirus.”. https://www.ncbi.nlm.nih.gov/pubmed/28163914. 2017 Jan 26.

Preventing norovirus outbreaks. (2019, December 23). Retrieved March 28, 2021, from
https://www.cdc.gov/vitalsigns/norovirus/index.html

Gutierrez, Graciela, “Solving a 48-year-old mystery: scientists succeed at growing noroviruses


in human intestinal cell cultures in the lab”. https://www.bcm.edu/news/molecular-virology-
and-microbiology/norovirus-infection-grown-in-intestinal-cells. 2016 August 25

Karst, Stephanie M, Wobus, Christiane E, Goodfellow, Ian G, Green, Kim Y, & Virgin, Herbert
W. (2014). Advances in Norovirus Biology. Cell Host & Microbe, 15(6), 668–680.
https://doi.org/10.1016/j.chom.2014.05.015
Recent Advances in Understanding Norovirus
Literature Review
HLTH 499 Capstone
Rachelle Martinez
March 28, 2021

Kim, Yunjeong, Galasiti Kankanamalage, Anushka C, Chang, Kyeong-Ok, & Groutas, William C.
(2015). Recent Advances in the Discovery of Norovirus Therapeutics. Journal of Medicinal
Chemistry, 58(24), 9438–9450. https://doi.org/10.1021/acs.jmedchem.5b00762

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