Efficient production of a lentiviral system for displaying Crimean-Congo hemorrhagic fever virus glycoproteins reveals a

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ORIGINAL ARTICLE

Efficient production of a lentiviral system for displaying Crimean‑Congo hemorrhagic fever virus glycoproteins reveals a broad range of cellular susceptibility and neutralization ability Abbas Ahmadi Vasmehjani1 · Mostafa Salehi‑Vaziri2,3 · Kayhan Azadmanesh4 · Ahmad Nejati1 · Mohammad Hassan Pouriayevali3 · Mohammad Mahdi Gouya5 · Mahboubeh Parsaeian6 · Shohreh Shahmahmoodi1,7 Received: 4 October 2019 / Accepted: 2 February 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020

Abstract Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease with a mortality rate of up to 50% in humans. To avoid safety concerns associated with the use of live virus in virus neutralization assays and to detect human serum neutralizing antibodies, we prepared lentiviral particles containing the CCHF glycoprotein (lenti-CCHFV-GP). Incorporation of the GP into the lentiviral particle was confirmed by electron microscopy and Western blotting. Lenti-CCHFV-GP was found to be able to infect a wide range of cell lines, including BHK-21, HeLa, HepG2, and AsPC-1 cells. In addition, lenti-CCHFV-GP was successfully used as an alternative to CCHFV for the detection of neutralizing antibodies. Sera collected from CCHF survivors neutralized lenti-CCHFV-GP particles in a dose-dependent manner. Our results suggest that the lenti-CCHFV-GP pseudovirus can be used as a safe tool for neutralization assays in low-containment laboratories.

Introduction Handling Editor: Hideki Ebihara. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0070​5-020-04576​-9) contains supplementary material, which is available to authorized users. * Shohreh Shahmahmoodi [email protected] 1



Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran 1417613151, Iran

2



Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran

3

Department of Arboviruses and Viral Hemorrhagic Fevers (National Reference Laboratory), Pasteur Institute of Iran, Tehran, Iran

4

Department of Virology, Pasteur Institute of Iran, Tehran, Iran

5

National Communicable Disease Control Centre, Ministry of Health and Medical Education, Tehran, Iran

6

Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

7

Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran







Crimean-Congo hemorrhagic fever (CCHF) is a serious public health concern because of its high mortality rate (50%), its potential for person-to-person transmission, and the lack of specific therapies or licensed vaccines [2, 15]. Since the first description of CCHF in 1944 in Crimea, this disease has been reported in more than 31 countries in Africa, Asia, and Europe, making it the most widespread tick-borne viral infection in humans around the world [12, 21]. Recently, the World Health Organization (WHO) has categorized CCHF as one of the epidemic-prone eme