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RNA Modulates the Interaction Between Influenza A Virus Non-Structural Protein 1 and Human Poly (A) Binding Protein 1

  • Author(s): Arias, Bryan H.
  • Advisor(s): Joseph, Simpson
  • et al.
Abstract

Influenza A Virus (IAV) is a seasonal virus that infects millions of people and causes thousands of deaths per year. This (-)-sense RNA virus infects human lung epithelial cells where it synthesizes (+)-sense messenger RNAs (mRNAs) for the purposes of using host machinery to generate new IAV virions. Non-Structural Protein 1 (NS1) is an IAV protein that is known to stimulate the translation of viral mRNAs in order to efficiently produce new virions. How NS1 is able to differentiate between viral and non-viral mRNAs is not fully understood. Previous studies have indicated that NS1 binds to the unique 5’-UTRs of viral mRNA and recruits PABP1 and eIF4G proteins, which leads to viral protein production.

To better understand how NS1 stimulate the translation of viral mRNA, chapter 1 and 2 discuss the previous research about IAV and the structure and function of NS1 and PABP1. In order to determine whether NS1 preferentially binds to the 5’-UTR of viral genes, several short RNA substrates from viral and non-viral sequences were tested using anisotropy as presented in chapter 3. Chapter 4 examines the binding of NS1 with longer, viral and non-viral mRNAs using filter binding to better understand the interactions with more representative RNAs. Interestingly, data using both fluorescence anisotropy and filter binding assays show that NS1 does not preferentially bind to viral mRNAs.

Although NS1 does not preferentially bind to viral mRNA, the binding to RNAs may still affect NS1’s interaction with PABP1. Chapter 5 looks at the interaction between NS1 and PABP1 using FRET to determine whether RNA regulates the interaction. Using viral and non-viral RNA, I show that the NS1-PABP1 interaction is indeed modulated by RNA.

The information presented here shows that the model where NS1 binds preferentially to the 5’-UTR of viral mRNA to stimulate translation is not accurate. Instead, the data suggests that NS1 can enhance translation of any mRNA. Chapter 6 discusses the results and proposes an alternative model for NS1 regulation of the host machinery during infection.

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