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Countering Zika Virus: The USAMRIID Response

  • Robert G. Lowen
  • Thomas M. Bocan
  • Christopher D. Kane
  • Lisa H. Cazares
  • Krishna P. Kota
  • Jason T. Ladner
  • Farooq Nasar
  • Louise Pitt
  • Darci R. Smith
  • Veronica Soloveva
  • Mei G. Sun
  • Xiankun Zeng
  • Sina Bavari
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1062)

Abstract

The United States Army Medical Research Institute of Infectious Diseases (USAMRIID) possesses an array of expertise in diverse capabilities for the characterization of emerging infectious diseases from the pathogen itself to human or animal infection models. The recent Zika virus (ZIKV) outbreak was a challenge and an opportunity to put these capabilities to work as a cohesive unit to quickly respond to a rapidly developing threat. Next-generation sequencing was used to characterize virus stocks and to understand the introduction and spread of ZIKV in the United States. High Content Imaging was used to establish a High Content Screening process to evaluate antiviral therapies. Functional genomics was used to identify critical host factors for ZIKV infection. An animal model using the temporal blockade of IFN-I in immunocompetent laboratory mice was investigated in conjunction with Positron Emission Tomography to study ZIKV. Correlative light and electron microscopy was used to examine ZIKV interaction with host cells in culture and infected animals. A quantitative mass spectrometry approach was used to examine the protein and metabolite type or concentration changes that occur during ZIKV infection in blood, cells, and tissues. Multiplex fluorescence in situ hybridization was used to confirm ZIKV replication in mouse and NHP tissues. The integrated rapid response approach developed at USAMRIID presented in this review was successfully applied and provides a new template pathway to follow if a new biological threat emerges. This streamlined approach will increase the likelihood that novel medical countermeasures could be rapidly developed, evaluated, and translated into the clinic.

Keywords

Animal models of infection Next-generation sequencing High content imaging PET imaging Rapid medical countermeasure to emerging viruses 

Notes

Acknowledgments

Funding for ZIKV research was provided by DARPA. The authors would like to thank Dr. Michael Wiley, Ms. Karla Prieto, Mr. Daniel Reyes, Ms. Elyse Nagle, Dr. Mariano Sanchez-Lockhart and Dr. Gustavo Palacios for their contributions toward the genomic characterization. The authors would like to acknowledge Mr. Kyle Kuszpit and Robert Stafford for their assistance in performing the imaging studies and Drs. Xiang Zhang, Falguni Basuli, and Rolf Swenson from the Imaging Probe Development Center at NIH for providing the PET radiotracers. The authors would also like to thank Mr. Brandon Kline and Ms. Kathy Kuehl for EM support and Ms. Tara Kenny, Ms. Xiaoli Chi, Mr. Rouzbeh Zamani, Mr. Glenn Gomba, Mr. Collin Dube for their support of HCI screening work.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Robert G. Lowen
    • 1
  • Thomas M. Bocan
    • 1
  • Christopher D. Kane
    • 1
  • Lisa H. Cazares
    • 1
  • Krishna P. Kota
    • 1
  • Jason T. Ladner
    • 2
  • Farooq Nasar
    • 1
  • Louise Pitt
    • 1
  • Darci R. Smith
    • 1
  • Veronica Soloveva
    • 1
  • Mei G. Sun
    • 1
  • Xiankun Zeng
    • 1
  • Sina Bavari
    • 1
  1. 1.U.S. Army Medical Research Institute of Infectious DiseasesFt. DetrickUSA
  2. 2.The Pathogen and Microbiome InstituteNorthern Arizona UniversityFlagstaffUSA

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