About

Our laboratory is contributing to pandemic preparedness by elucidating the details of genome replication using the most tractable models for several families of RNA viruses.

Viral infection poses a never-ending threat to human health. It is nearly impossible to predict the next viral outbreak of concern because of the ever-evolving nature of viruses and the potential for new human pathogens to originate in non-human members of the animal kingdom. Readiness for a viral epidemic of unknown etiology requires broad-spectrum, antiviral therapeutics and universal strategies for viral attenuation, for example strategies based on attenuating changes to the activity of a conserved viral enzyme. Our laboratory has had a longstanding interest in discovering fundamental biological knowledge relevant to the treatment and/or prevention of viral infection.

The era of biology on the single-cell level is well underway, and we have become a standard-bearer for “single-cell virology.” Currently, most studies emphasize the between-cell variability of populations in terms of gene expression. Even those studies with viral infection as the focus emphasize end-point differences in yield of virus or viral nucleic acid. No doubt there is much to learn from these studies. However, there is also much to be learned by evaluating viral infection dynamics on the single-cell level.

We have developed a microfluidics-based, cell-culturing, imaging, and data-analysis platform that enables high-throughput, kinetic analysis of single, isolated cells infected with a viral population harboring fluorescent reporters. We have observed unprecedented between-cell variation in the onset, speed, and yield of replication, as well as variation in lysis, both if and when lysis occurs. Our studies demonstrate that analysis of viral infection dynamics on the single-cell level yields knowledge about virus-host interactions and the response of the host to viral infection eluded by population methods.

Preprints & Publications

• Xiao, Z., Das, A., Jain, A., Anderson, T.K., Cameron, C.E., Arnold, J.J., Dulin, D., and Kirchdoerfer, R.N. Incorporation of arabinose-CTP and arabinose-UTP inhibits viral polymerases by inducing long pauses. (2025). J Biol Chem 302(1), 111027.
• Aponte-Diaz, D., Jain, A., Harris, J.M., Arnold, J.J., and Cameron, C.E. Minimal polymerase-containing precursor required for Chikungunya virus RNA synthesis. (2025). Viruses 17(12), 1556.
• Arnold, J.J., Braet, S.M., Vieira, L.C., Moustafa, I.M., Gohara, D.W., Fecko, J.A., Su, Y.N., Jain, A., Aponte-Diaz, D., Wilke, C.O., Anand, G.S., Yennawar, N.H., and Cameron, C.E. A fold switch regulates conformation of an alphavirus RNA-dependent RNA polymerase. (2025). bioRxiv (preprint), 2025.09.18.676892. (in press in Nucleic Acids Res)
• Muthu Ramalingam, B., Sears, J.D., Talbot, K.M., Su, Y.N., Houliston, S., Hossain, M.A., Davis-Gilbert, Z.W., Zhao, C., Oh, H.J., Brown, P.J., Sanders, M.K., Moorman, S.R., Ojha, D., Burdick, J.E., Law, I., Morales, N.L., Martinez, S.A., Loppnau, P., Garcia Perez, J., Drobish, A.M., Morrison, T.E., Streblow, Z.J., Streblow, D.N., Arrowsmith, C.H., Vargason, A., Couñago, R.M., Halabelian, L., Arnold, J.J., Cameron, C.E., Moorman, N.J., Heise, M.T., and Willson, T.M. Identification of direct-acting nsP2 helicase inhibitors with antialphaviral activity. (2025). J Med Chem 68(14), 14514–14536.
• Arnold, J.J., Martinez, A., Jain, A., Liu, X., Moustafa, I.M., and Cameron, C.E. Mechanism of forced-copy-choice RNA recombination by enteroviral RNA-dependent RNA polymerases. (2025). ACS Bio Med Chem Au 5(3), 427–446.
• Li, Y., Gupta, A., Papas, B.N., Aponte-Diaz, D., Harris, J.M., Misumi, I., Whitmire, J.K., Cameron, C.E., Morgan, M., and Lemon, S.M. Noncanonical poly(A) polymerase TENT4 drives expression of subgenomic hepatitis A virus RNAs in infected cells. (2025). Viruses 17(5), 665.
• Aponte-Diaz, D., Harris, J.M., Kang, T.E., Korboukh, V., Sotoudegan, M.S., Gray, J.L., Yennawar, N.H., Moustafa, I.M., Macadam, A., and Cameron, C.E. Non-lytic spread of poliovirus requires the nonstructural protein 3CD. (2025). mBio 16(1), e03276-24.
• Liu, W., Wilke, C.O., Arnold, J.J., Sotoudegan, M.S., and Cameron, C.E. Single-cell virology: On-chip, quantitative characterization of the dynamics of virus spread from one single cell to another. (2024). Viruses 16(11), 1659.