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Our Science

Our lab is interested in several interrelated areas that answer fundamental questions:

  • How do viruses infect cells, and how do cells respond to infection?

  • How does metabolism affect viral infection, and how do viruses manipulate cellular metabolism?

  • How can we combat virus infection with antivirals?

  • Can we find new sources of antivirals?

  • What other cool things can we discover about cells and viruses?

We answer these questions in several ways:

  • We infect cells and measure how the virus replicates.

  • We investigate signaling pathways that are important for the cell and virus.

  • We measure cellular metabolites to understand how metabolism changes during infection.

  • We perform drug screens and follow-up antiviral development to find new antivirals.

  • We find creative and exciting new sources of antivirals

Polyamines in viral infection: The OG Mounce Lab
When the Mounce lab was established in 2017, we started by examining how these really cool metabolites called polyamines regulate virus infection Polyamines are small, positively charged molecules that have several functions in the context of the cell, including roles in nucleic acid conformation, regulating the cell cycle, and altering cellular translation. In addition, polyamines are important for many different viruses, from chikungunya virus to enterovirus to rabies virus. Since this time, we have made great discoveries regarding polyamines:

  • A diverse array of viruses rely on polyamines for their replication

  • Polyamines contribute to viral translation, transcription, protease activity, attachment, and infectivity

  • Viruses manipulate polyamines during infection to promote their replication

  • Viruses evolve in response to polyamine metabolism 

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Our first paper!

Led by InDIRI MS student Courtney Dial (now Dr. Dial!), we found that polyamines contribute to Coxsackievirus protease activity. If a cell doesn't have polyamines, the viral proteases don't function well. Antivirals targeting polyamines are effective at least in part because they reduce protease activity.

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  • Why it matters: Coxsackievirus relies on polyamines for replication, and this paper was the first to show that polyamines contribute to protease activity. Drugs that disrupt polyamine metabolism limit viral infection because they affect viral protease activity.

  • One-sentence takeaway: Polyamines promote Coxsackievirus protease activity.

  • Fun fact: We worked with Susan Baker's lab to develop the protease activity assay - it's a popular assay within the department!​

Polyamines in cellular processes: 
We always knew that polyamines are important for the cell - even since Antonie van Leeuwenhoek first saw them under the microscope. Our lab has been working to understand how polyamines contribute to cellular health, specifically by looking at metabolism in those cells. We've made a number of exciting discoveries in this field, including:

  • Polyamines contribute to cholesterol synthesis in the cell by enhancing translation of SREBP2.

  • Mitochondria rely on polyamines for their structure.

  • Polyamines promote the expression of viral attachment factors on the cell surface.

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Polyamines promote cholesterol synthesis!

Led by IPBS PhD student Mason Firpo (now Dr. Firpo), this manuscript provides the first mechanistic link between polyamines and cholesterol synthesis. Polyamines are involved in this unique pathway called hypusination that enhances the translation of SREBP2, a key transcriptional regulator for cholesterol synthesis. Depleting polyamines also depletes cholesterol from cells, and this limits virus infection.

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  • Why it matters: Cholesterol is a key cellular component, and both cells and viruses rely on cholesterol. This study is the first to mechanistically link polyamines to cholesterol metabolism, as well as linking this to viral infection, specifically through viral attachment.

  • One-sentence takeaway: Polyamines promote cholesterol synthesis through SREBP2 translation.

  • Fun fact: We knew for years that cholesterol was reduced in polyamine-depleted cells, but Mason was the first to dive into the lipid side of cellular metabolism!​

Antiviral Drug Screens & Discovering New Antivirals:
Viruses are masters at infection, and we have very few antivirals to combat them. There are several notable cases where antivirals are available for infected individuals: HIV-1, COVID, or hepatitis C. However, for most viruses, we don't have antivirals approved for use. Toward the goal of developing antivirals, we undertake drug screening, where we screen hundreds of compounds for antiviral activity against a virus. We've now published this approach three times, with three different viruses (Coxsackievirus, chikungunya virus, and La Crosse virus), and in each of those instances, we have identified and characterized new molecules with antiviral activity. You never know what antiviral you're going to get! 

  • Bisacodyl is a laxative, but we have found that it is active against chikungunya virus.

  • We found that ionophores inhibit La Crosse virus infection, as well as several other bunyaviruses.

  • We discovered antivirals that work against both persistent and acute Coxsackievirus infection.

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Our first published drug screen!

Led by InDIRI MS student Zach Sandler, we used La Crosse virus, an interesting but rarely-studied bunyavirus, and we developed a pipeline to screen antivirals. Using the NIH's Developmental Therapeutic Program, we tested hundreds of compounds against La Crosse virus, and we chose to further investigate ionophores, which we found potently antiviral.

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  • Why it matters: Drug screens can identify new compounds with antiviral activity in an unbiased manner. La Crosse virus is a poorly studied virus, and no antivirals are available to treat it. We found that ionophores are a class of molecule that holds promising antiviral activity.

  • One-sentence takeaway: La Crosse virus is sensitive to molecules that disrupt ion flow within the cell.

  • Fun fact: Zach spent weeks developing and optimizing a new antiviral screening protocol, which we still use all the time in the lab!

Polymicrobial interactions and new sources of antivirals: Coming soon! 
We like to find antivirals, but we also want to find new and exciting sources of antivirals. Spearheaded by IPBS PhD student Caroline Thomas, we have taken a new approach (to our lab at least!) of finding unique environmental samples with antiviral activity and isolating antiviral molecules from those samples. We are ecstatic to explore this new arena for the lab, and we can't wait to share the results with you!

Our Collaborators:
We work closely with scientists around the world to make our science the best that it can be. Here are some of the people that we currently work with or that we have collaborated with in the past, including our papers! 

Our viral model systems: 
We use several model systems in the laboratory to better understand how viruses are similar or divergent. By studying how different viruses respond to the same stimuli (e.g., polyamine depletion), we can better understand how viruses are related, how they have convergently evolved to replicate, and identify common pathways that could serve as potent broad-spectrum antiviral targets. It's also exciting to see how viruses replicate within cells, including plaque assays!

Here are some of the viruses that we work with in the laboratory: 

  • Alphaviruses like chikungunya virus or Mayaro virus

  • Enteroviruses like Coxsackievirus

  • Bunyaviruses like Rift Valley fever virus or La Crosse virus

  • Flaviviruses like Zika virus

  • Vaccinia virus

  • Measles virus

  • Influenza virus

The Mounce Lab | Bryan Mounce

Loyola University Chicago
Department of Microbiology and Immunology
Stritch School of Medicine
2160 South First Avenue
Maywood, Illinois

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