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Full-Text Articles in Medicine and Health Sciences

Reverse Zoonosis Of Pandemic A(H1n1)Pdm09 Influenza Viruses At The Swine/Human Interface, Daniel Gene Darnell Oct 2019

Reverse Zoonosis Of Pandemic A(H1n1)Pdm09 Influenza Viruses At The Swine/Human Interface, Daniel Gene Darnell

Theses and Dissertations (ETD)

The 2009 pandemic influenza A(H1N1)pdm09 virus emerged from the swine population. Despite frequent zoonotic events, swine influenza viruses had not become established in humans previously and little is known about host-barriers which prevent swine influenza viruses from efficiently infecting humans. Thus, the emergence of the H1N1pdm09 viruses in humans and the subsequent reverse zoonoses back to swine offered an extremely valuable opportunity to expand current knowledge. We used our active swine farm surveillance platform in combination with viruses from the USDA surveillance program to look for evidence of interspecies transmission of H1N1pdm09 viruses in the US. We found phylogenetic evidence …


Roles Of Γδ T Cells In Influenza Infections And Methods For Tcr Expression And Characterization, Xizhi Guo May 2019

Roles Of Γδ T Cells In Influenza Infections And Methods For Tcr Expression And Characterization, Xizhi Guo

Theses and Dissertations (ETD)

"Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses associated with immune cell migration/activation and cytokine/chemokine release, can be induced after infections. Recent studies have painted a complex picture of viral clearance and tissue repair in adults. The immune responses in neonatal influenza infections and the potential methods to engineer antigen-specific T cells for immunotherapy against cancers and infections will be the focus of this dissertation." "Compared to adults, infants suffer higher rates of hospitalization, severe clinical complications, and mortality due to influenza infection. We found that …


Evaluating The Potential Of Repurposing Commercially Available Drugs For The Treatment Of Viral Infections, Brennan Connor Mcewan May 2019

Evaluating The Potential Of Repurposing Commercially Available Drugs For The Treatment Of Viral Infections, Brennan Connor Mcewan

Undergraduate Honors Capstone Projects

Viral infections that are often overlooked as common seasonal illnesses such as influenza can rapidly become a public threat. They threaten society as new, more dangerous strains of these common viruses emerge and as strains develop resistance to current vaccines and antiviral treatments (Kochanek, Murphy, Xu, & Tejada-Vera, 2014). To combat this, the development of antiviral treatments with novel mechanisms of action is essential. Repurposing drugs instead of developing new drugs can save years of development time and hundreds of millions of dollars (DiMasi, Hansen, & Grabowski, 2003). To support the effort to discover drugs with unique mechanisms of action, …


Structural And Functional Insights Into Influenza A Virus Ns1-Mediated Rig-I Antagonism, Alexander Jureka Jan 2019

Structural And Functional Insights Into Influenza A Virus Ns1-Mediated Rig-I Antagonism, Alexander Jureka

All ETDs from UAB

The influenza virus non-structural protein 1 is well known to antagonize the host innate immune response through its interaction with the innate immune sensor, retinoic acid induc-ible gene I (RIG-I). While the complete mechanism of the NS1:RIG-I interaction remains unclear, we were the first to demonstrate a direct interaction between the NS1 RNA-binding domain (NS1RBD) from the 1918H1N1 influenza virus and the second caspase activa-tion and recruitment domain (CARD2) of RIG-I using NMR. In addition, we also identi-fied that mutation of Arg 21 in the 1918H1N1 NS1RBD to Gln (R21Q) completely abrogated the NS1:CARD2 interaction. Given that CARD2 plays a …


Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter Jan 2019

Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter

All ETDs from UAB

The influenza A virus (IAV) non-structural protein 1 (NS1) is a highly multifunctional viral protein responsible for antagonizing the type-I interferon (IFN) response to infection. NS1 has therefore been identified as a potentially effective target for the development of novel anti-influenza compounds. Furthermore, it is important to understand the molecular underpinnings driving NS1 function to more effectively elucidate antiviral targets. In this dissertation, we have contributed significant insight into NS1’s potential as an antiviral target, and the structure-function relationships driving its activity in an infected cell. First, we structurally characterized the binding of two known influenza inhibitors (A9 and A22) …