The Hardy Lab
Viral and Host Determinants of Alphavirus Infection
Current Projects
Areas of active research in the lab.
1. Virus-host interactions shaping alphavirus infection
Typical virus infection in any host cell type is associated with a multitude of interactions occurring between different viral factors or between viral and host factors. Examples include interactions between viral capsid proteins and viral RNA that take place at every stage of the replication cycle (depicted above), or interactions between host heterogeneous ribonucleoproteins (hnRNPs), viral non-structural proteins and viral RNA. Our lab is interested in identifying and characterizing host-virus interactions required for successful virus propagation and/or virus restriction in vertebrate and invertebrate cell types.
2. Molecular mechanisms of pathogen blocking
The endosymbiotic bacterium Wolbachia pipientis is a novel biocontrol agent presently being used to curb transmission of arboviruses across the world. This vertically transmitted microbe functions as a natural gene drive and its presence within the arthropod cells result in the inhibition of different positive-sense single-stranded RNA viruses. However, the cellular mechanism of this pathogen blocking phenotype remains unclear. In collaboration with Dr. Irene Newton's lab at IU, our goal is to investigate this phenomenon using a combination of in vivo and cell culture models of different arthropod species, Drosophila melanogaster, Aedes albopictus and Aedes aegypti, harboring both native and non-native Wolbachia strains (depicted above).
3. Effect of RNA modifications on alphavirus infection
Our recent findings suggest a novel role of host RNA methyltransferase proteins in regulating virus infection in arthropods. We are presently interested in exploring the role of RNA modifications, particularly 5-methylcytosine (m5C) signatures on viral and host RNA species in shaping alphavirus replication, dissemination, and transmission across different hosts and cell types.
Recent Lab Publications
Papers from the lab highlighting our most recent findings.
Host-Dependent Modifications of Packaged Alphavirus Genomic RNA Influence Virus Replication in Mammalian Cells
John M Crawford, Liewei L Yan, Hani Zaher, Richard W Hardy. Viruses 2022, 14(12): 2606. https://doi.org/10.3390/v14122606
Interactions between capsid and viral RNA regulate Chikungunya virus translation in a host-specific manner
Lauren M Kiser, Kevin J Sokoloski, Richard W Hardy. Virology 2021, 560, 34-42. https://doi.org/10.1016/j.virol.2021.04.009
Wolbachia and virus alter the host transcriptome at the interface of nucleotide metabolism pathways
Lindsey ARI, Bhattacharya T, Hardy RW, Newton ILG, bioRxiv 2020.06.18.160317; doi: https://doi.org/10.1101/2020.06.18.160317
Viral RNA is a target for Wolbachia-mediated pathogen blocking
Bhattacharya T, Newton ILG, Hardy RW. Viral RNA is a target for Wolbachia-mediated pathogen blocking. PLoS Pathogens 2020 16(6): e1008513. https://doi.org/10.1371/journal.ppat.1008513
Encapsidated Host Factors in Alphavirus Particles Influence Midgut Infection of Aedes aegypti
David Mackenzie-Liu, Kevin J Sokoloski, Sarah Purdy, Richard W Hardy. Viruses 2018, 10(5), 263;https://doi.org/10.3390/v10050263
Identification of Interactions between Sindbis Virus Capsid Protein and Cytoplasmic vRNA as Novel Virulence Determinants
Kevin J Sokoloski, Lauren M Nease, Nicholas A May, Natasha N Gebhart, Claire E Jones, Thomas E Morrison, Richard W Hardy. PLoS Pathogens 2017, 13(6): e1006473. https://doi.org/10.1371/journal.ppat.1006473
For a full list of publications, head over to PubMed by clicking the word cloud above.
Primary Research Articles:
- R. K. Patel and R. W. Hardy. 2012. A Role for PI3K-Akt-TOR Pathway During Sindbis Virus Replication in Arthropods. J. Virol. 86 (7): 3595-3604.
- K. J. Sokoloski, C. A. Hayes, M. P. Dunn, J. L. Balke, R. W. Hardy* and S. Mukhopadhyay*. 2012. Sindbis virus infectivity improves during the course of infection in both mammalian and mosquito cells. Virus Res. 167 (1): 26-33. *co-corresponding authors
- C. Ji, R. J. Arnold, K. J. Sokoloski, R.W. Hardy, H. Tang and P. Radivojac. 2013. Extending the coverage of spectral libraries: a neighbor-based approach to predicting intensities of peptide fragmentation spectra. Proteomics. 13 (5):756-765.
- Z. Huang, M. Kingsolver, V. Avadhanula and R. W. Hardy. 2013. An antiviral role for antimicrobial peptides during the arthropod response to Alphavirus replication. J. Virol. 87 (8):4272-4280.
- R. K. Patel, A. J. Burnham, N. N. Gebhart, K. J. Sokoloski and R. W. Hardy. 2013. Role for subgenomic mRNA in host translation inhibition during Sindbis virus infection of mammalian cells. Virology. 441 (2): 171-181.
- K. J. Sokoloski, N. Liu, C. A. Hayes, A. J. Snyder, S. Mukhopadhyay, and R. W. Hardy. 2013. Encapsidation of host-derived factors correlates with enhanced infectivity of Sindbis Virus. J. Virol. 87 (22): 12216-12226
- K. J. Sokoloski, S. Mukhopadhyay, T. Morrison and R.W. Hardy. 2015. Noncapped Alphavirus genomic RNAs and their role during infection. J. Virol. 89 (11): 6080-6092.
- Bhattacharya T, Newton IL, Hardy RW. Wolbachia elevates host methyltransferase expression to block an RNA virus early during infection. PLoS pathogens. 2017 Jun;13(6).
- Bhattacharya T, Rice DW, Hardy RW, Newton I. Adaptive evolution in DNMT2 supports its role in the dipteran immune response. bioRxiv. 2020 Jan 1.
Review Articles:
- †M. B. Kingsolver, Z. Huang and R. W. Hardy. 2013. Insect antiviral innate immunity: pathways, effectors, and connections. Invited Review for J. Mol. Biol. 425 (24): 4921-4936.
- †J. C. Rupp, K. J. Sokoloski, N. N. Gebhart and R. W. Hardy. 2015. Alphavirus RNA synthesis and non-structural protein functions. J. Gen. Virol. 96 (9): 2483-2500.
- Lindsey AR*, Bhattacharya T*, Newton IL, Hardy RW. Conflict in the Intracellular Lives of Endosymbionts and Viruses: A Mechanistic Look at Wolbachia-Mediated Pathogen-blocking. Viruses. 2018 Mar 21;10(4):141. *Denotes equal contributions
Current members of the lab
Meet the people behind the science.
Principal Investigator
Provost Professor, Biology
Director, Human Biology
Associate Dean for Undergraduate Education
Email: rwhardy@indiana.edu
Nicole Stark
Ph.D. Candidate
I am interested in understanding the mechanism behind how Wolbachia inhibits the replication of alphaviruses. Outside of the lab, I enjoy practicing yoga and watching documentaries.
Email: nikstark@indiana.edu
Jordan Geisert
Ph.D. Candidate
My research explores how alphaviruses have developed mechanisms to expand the coding capacity of a small genome. Specifically, I look at programmed ribosomal frameshifting and multifunctional proteins (and more importantly these two strategies coupled). I additionally am the resident meme-maker of the lab, and love mentoring undergraduates!
Email: jgeisert@iu.edu
@jordan_geisert
Davis Moline
Graduate Student
My research interests center around the interaction between viral and host proteins, and how host environments can change the ability for a virus to replicate. In my free time, I enjoy playing board games and painting models
Email: damoline@iu.edu
Emily Layton
Ph.D. Candidate
Under the dual mentorship of Dr. Richard Hardy and Dr. Irene Newton, I’m working to identify the virus genes and insect host genes necessary for Wolbachia to inhibit viral replication. In addition to my research, I’m passionate about making sci-art to communicate science to broader audiences.
@emilymlayton | emilylayton.com
Email: laytonem@iu.edu
