Jeremiah Athmer defends PhD thesis

Jeremiah Athmer with Stanley Perlman

Jeremiah Athmer successfully defended his PhD thesis, "New Insights into NSP15 protein and RNA elements during mouse hepatitis virus infection" on Friday, October 20, 2017. Jeremiah appears with his mentor, Dr. Stanley Perlman.

About Jeremiah

Jeremiah grew up in Dixon, a small town in rural Missouri. At a young age he spent a lot of time deconstructing anything that wasn’t working, driven to understand how things worked. Jeremiah’s drive toward viruses and a PhD in Microbiology began in high school. Jeremiah’s high school science teacher, Mrs. Alexander, postulated that viruses could be used to positively affect humans. This question changed the way Jeremiah viewed science and sparked his interest in the scientific unknown, setting him on a course to study viruses and obtain his PhD in Microbiology.

Jeremiah attended Missouri State University in Springfield, MO. In the fall of his freshman year he started working in Dr. Paul Durham’s lab studying diagnostic markers of migraine in saliva. In 2012 Jeremiah began his PhD work at Iowa in the Biosciences program and eventually found a home in Dr. Stanley Perlman’s lab, studying the molecular virology of coronaviruses. Over the last year he has interned at UIVentures and UIRF working to develop an understanding of the intersection of business and science. Jeremiah plans on utilizing this knowledge and his assay development skills to transition into in vitro diagnostic development.

Outside of the lab, Jeremiah enjoys spending time with his wife, Brittany,  and dog, Autumn. He enjoys disc golf, video games with friends, and hiking. Jeremiah and Brittany enjoy camping and plan on returning to Colorado for more hiking. Jeremiah and Brittany are avid St. Louis Cardinals fans, and want to see them play in each MLB stadium.


The nonstructural protein 15 (nsp15) locus in Lineage A β-coronaviruses has two important functions during replication. The encoded endoribonuclease protein is conserved among coronaviruses. The RNA cleavage function of the nsp15 protein is still not fully understood, but recent evidence suggests it may be involved in both replication and inhibition of viral sensing of double stranded RNA. In Lineage A β-coronaviruses, the nsp15 locus also contains an inserted RNA stem loop that serves as a viral packaging signal (PS). The PS is essential for selectively packaging viral genomic RNA (gRNA) while restricting the incorporation of sub-genomic RNAs (sgRNAs) into the virion. While the PS is required for selective packaging, it is not required for nsp15 protein function or viral replication. Utilizing this region I have studied the interactions of nsp15 protein and the effect of selective packaging on virulence.

The coronavirus nonstructural proteins are responsible for forming the replication/ transcription complex (RTC) and creating an environment conducive to viral replication. The RTC is an intricate complex of viral and host proteins with an unknown composition. While all nsps studied to date localize to sites of replication, the interactions between these proteins are not fully understood. My studies of the interactions and localization of Nsp15 were conducted using a novel in situ hemagglutinin epitope tag. My data suggest nsp15 interacts with specific proteins in the RTC.

During coronavirus replication two species of viral RNA are replicated, gRNA and sgRNA. gRNA is selectively packaged over sgRNA, which is determined by the PS, a 95 base pair stem-loop structure in the nsp15 locus. This RNA motif is sufficient for the packaging of nonviral RNAs and has been shown to interact with the M protein from MHV. Moreover, when this RNA motif is deleted from MHV, (MHVPS-) selective packaging is lost during infection as sgRNAs comprise a large percentage of packaged viral RNA. I tested the effect of selective packaging on viral pathogenesis and found that mice infected with MHVPS- had significantly better outcomes compared to MHVWT infected mice. The pathogenesis of MHVPS- was restored in mice deficient in IFN signaling. These data indicate that the PS of MHV is an uncharacterized MHV virulence factor, which may act by preventing an increased IFN response during infection.

Wednesday, November 8, 2017