Biochemistry and Molecular Biology
Penn State Science
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Moriah L. Szpara

Moriah L. Szpara

Main Content

  • Assistant Professor of Biochemistry & Molecular Biology
W-208 Millennium Science Complex
University Park, PA 16802
Phone: (814) 867-0008

Research Interests

Neurovirology, genomics of pathogen variation, neuron-virus relationships

Graduate Programs

BG, BMMBMCIBS, NEURS

Research Summary

A variety of viruses infect the human nervous system, often with severe consequences. While vaccines have largely defeated the paralysis caused by polio, other viruses such as rabies, West Nile virus, and herpes simplex virus (HSV) continue to cause neurological infections that require clinical intervention. More than 70% of adults in the United States carry HSV, whether they know it or not. HSV causes recurrent genital and oral lesions (e.g. cold sores), and in rare cases can progress to cause potentially fatal brain infections. Although not all of those infected experience noticeable symptoms, human hosts have a permanent relationship with this virus. HSV has a unique ability to establish lifelong latency in neurons. The consequences of HSV latency for the neurons that harbor this pathogen are not well understood. Our laboratory aims to address this question and search for improved therapeutics using a combination of virology, neurobiology, next generation sequencing technologies, and bioinformatics.

Viral variation and neurovirulence

We have known for a long time that strains of HSV-1 are genetically variable, and new deep sequencing approaches allow us to fully define these differences and begin to understand how they affect phenotype. For example, previous work has shown that attenuated strains of HSV-1 do not replicate well in the nervous system, causing little disease in animal models. In contrast, highly virulent strains cause lethal encephalitis in days. Previous tools to map differences between HSV strains included restriction digest mapping or candidate-gene approaches. Now we can readily sequence the full genomes of many strains, use bioinformatics to associate variations with virulence phenotypes, and then test these genetic associations experimentally. We anticipate that differences in viral virulence genes contribute to the differing symptoms and severity of HSV disease in humans.

Neuronal consequences of infection

We would like to better understand how HSV latency affects the host neuron and its neighboring cells. In lab experiments, HSV infection of neurons has been associated with changes in neuropeptide release, neuronal firing rates, axon remodeling, and interferon production. However many factors remain unknown. While neurons are not specialized for immune control or attack, they do contain intrinsic cellular defenses. How are these cellular defenses and immune responses triggered by neurons? What is the viral counter-attack? Are neuronal defenses activated during viral reactivation, or only during the initial round of infection?  Features unique to neurons may present novel targets to block the progression of infection. We address the neurobiology of infection using a combination of neuronal cultures, in vivo models of infection, and high-throughput measurements of the host response.

Selected Publications

  • Szpara ML, Gatherer D, Ochoa A, Greenbaum B, Dolan A, Bowden RJ, Enquist LW, Legendre M, Davison AJ. Evolution and diversity in human herpes simplex virus genomes. (2014) J Virol, Jan; 88(2): 1209-27.
  • Szpara ML, Tafuri YR, Parsons L, Shamim SR, Verstrepen KJ, Legendre M, Enquist LW. A wide extent of inter-strain diversity in virulent and vaccine strains of alphaherpesviruses. (2011) PLoS Pathog 7(10): e1002282.
  • Szpara ML, Kobiler O, Enquist LW. A common neuronal response to alphaherpesvirus infection. (2010) J Neuroimmune Pharmacol. Sep; 5(3): 418-27.
  • Szpara ML, Parsons L, Enquist LW. Sequence variability in clinical and laboratory isolates of herpes simplex virus 1 reveals new mutations.(2010)J Virol. May; 84(10): 5303-13.

    Data website by M. Szpara & L. Parsons:  http://viro-genome.princeton.edu/HSV

  • Granstedt AE, Szpara ML, Kuhn B, Wang SS, Enquist LW. Fluorescence-based monitoring of in vivo neural activity using a circuit-tracing pseudorabies virus. (2009) PLoS One. Sep 9; 4 (9): e6923.