Single virus fingerprinting by widefield interferometric defocus-enhanced mid-infrared photothermal microscopy

Qing Xia, Zhongyue Guo, Haonan Zong, Scott Seitz, Celalettin Yurdakul, M. Selim Ünlü, Le Wang, John H. Connor () and Ji-Xin Cheng ()
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Qing Xia: Boston University
Zhongyue Guo: Boston University
Haonan Zong: Boston University
Scott Seitz: Boston University School of Medicine
Celalettin Yurdakul: Boston University
M. Selim Ünlü: Boston University
Le Wang: Boston University
John H. Connor: Boston University School of Medicine
Ji-Xin Cheng: Boston University

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Clinical identification and fundamental study of viruses rely on the detection of viral proteins or viral nucleic acids. Yet, amplification-based and antigen-based methods are not able to provide precise compositional information of individual virions due to small particle size and low-abundance chemical contents (e.g., ~ 5000 proteins in a vesicular stomatitis virus). Here, we report a widefield interferometric defocus-enhanced mid-infrared photothermal (WIDE-MIP) microscope for high-throughput fingerprinting of single viruses. With the identification of feature absorption peaks, WIDE-MIP reveals the contents of viral proteins and nucleic acids in single DNA vaccinia viruses and RNA vesicular stomatitis viruses. Different nucleic acid signatures of thymine and uracil residue vibrations are obtained to differentiate DNA and RNA viruses. WIDE-MIP imaging further reveals an enriched β sheet components in DNA varicella-zoster virus proteins. Together, these advances open a new avenue for compositional analysis of viral vectors and elucidating protein function in an assembled virion.

Date: 2023
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DOI: 10.1038/s41467-023-42439-4

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