Non-Structural Protein 1 (NS1) in Zika Virus Pathogenesis

Rumi Habib is a senior who is a Biology and Philosophy double major. He was awarded a Fall 2018 Independent Grant which he used to conduct research on the Zika Virus under Dr. Ioanna  Skountzou.

Although it was first discovered in 1947, the Zika virus didn’t enter the headlines until 2015. During the 2015-2016 epidemic, a wave of infants born with microcephaly, a neurodevelopmental condition that causes babies to have smaller than normal heads, resulted in the World Health Organization declaring the outbreak an international public health emergency. Viruses in the same family as the Zika virus include dengue, West Nile, and yellow fever. However, during the epidemic it emerged that Zika fever, even though milder than the diseases caused by its relatives, has some very unusual features. With microcephaly being the major one, it also emerged that Zika could be sexually transmitted, can infect the eye, can cause thrombocytopenia (low platelet levels), and in extremely rare cases can cause neurological issues in adults such as Guillain-Barré syndrome or myelitis¹. Though these symptoms rarely manifest, they suggest that the virus has a unique mode of pathogenesis(the way the virus spreads through the body during infection). However, exactly how Zika causes these symptoms is still poorly understood.

My research project is looking at the role of one of the virus’ 10 proteins, Non-Structural protein 1 (NS1), in its pathogenesis. The NS1 protein is unusual because cells infected with the virus secrete it into the bloodstream, something that should alert the immune system to the virus. Studies have found that NS1 based vaccines are effective², and so it is unclear why the virus “vaccinates” for itself during infection. Towards this project, we are currently still in the process of getting the NS1 protein by genetically engineering a line of cells to produce it, and upon isolating it will look at its effects in mice.

Working on the project, I have found that perhaps the most frustrating yet exciting part of the scientific process is its unpredictable nature. When reading scientific papers, experiments are presented in a way that makes projects seem linear. However, whether interpreting unexpected results, troubleshooting failed experiments, or figuring out how to move forward, the process of science is nothing like the clean-cut way in which it is presented.

 

One of the best parts of studying virology is that it’s an excuse to learn about all of biology. Working in virology combines approaches from various subfields such as genetics, biochemistry, evolutionary biology, and more. This is shown by how some of the greatest discoveries in biology, such as the fact that DNA stores information or the triplet code, came from studying viruses. Furthermore, there is direct translational value to virology research, and the study of viruses is useful not only in working towards curing diseases, but also for the development of new technologies. Examples of virus-based technologies on the horizon include oncolytic virus therapies for cancers, vectors for gene delivery, and recombinant expression systems for making proteins. The development of such technologies, and the constant emergence of new diseases such as Zika, mean that it is an exciting time to study virology. 

1.    Aliota, M. T., Bassit, L., Bradrick, S. S., Cox, B., Garcia-Blanco, M. A., Gavegnano, C., . . . Weaver, S. C. (2017). Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network. Antiviral Research, 144(Supplement C), 223-246. 

2.    Brault A.C., Domi A., McDonald E.M., Talmi-Frank D., McCurley N., Basu R., Robinson H.L., Hellerstein M., Duggal N.K., Bowen R.A., et al (2017). A Zika vaccine targeting NS1 protein protects immunocompetent adult mice in a lethal challenge model. Sci. Rep, 7:14769.

Visit the Undergraduate Research Programs website to learn more about applying for Independent

Research Grants.