Hepatocyte pathway alterations in response to in vitro Crimean Congo hemorrhagic fever virus infection

AbstractCrimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of World Health Organization, considering its potential to create a public health emergency and more importantly, the absence of efficacious drugs and/or vaccines regarding treatment. The highly lethal nature characteristic to CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design siRNAs that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 hours, nucleic acid from the supernatant was extracted for Droplet Digital PCR analysis. Among the investigated siRNAs we identified four effective candidates against all three segments of CCHF genome: one for the S and M segments, whilst two for the L segment. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAs in vitro. The most active siRNAs were demonstrated a specific inhibitory effect against CCHFV in a dose-dependent manner. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication in vitro. This promising result can be used in future anti-CCHFV therapy developments.

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Crimean-Congo Hemorrhagic Fever Virus Infection among Animals

Crimean-Congo Hemorrhagic Fever ◽

10.1007/978-1-4020-6106-6_13 ◽

2007 ◽

pp. 155-165 ◽

Cited By ~ 13

Author(s):

Aysegul Nalca ◽

Chris A. Whitehouse

Keyword(s):

Virus Infection ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus

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Antagonistic Antiviral Activity between IFN-Lambda and IFN-Alpha against Lethal Crimean-Congo Hemorrhagic Fever Virus In Vitro

PLoS ONE ◽

10.1371/journal.pone.0116816 ◽

2015 ◽

Vol 10 (2) ◽

pp. e0116816 ◽

Cited By ~ 8

Author(s):

Licia Bordi ◽

Eleonora Lalle ◽

Claudia Caglioti ◽

Damiano Travaglini ◽

Daniele Lapa ◽

...

Keyword(s):

Antiviral Activity ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Ifn Alpha ◽

Ifn Lambda

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Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro

Molecules ◽

10.3390/molecules25235771 ◽

2020 ◽

Vol 25 (23) ◽

pp. 5771

Author(s):

Fanni Földes ◽

Mónika Madai ◽

Henrietta Papp ◽

Gábor Kemenesi ◽

Brigitta Zana ◽

...

Keyword(s):

Rna Interference ◽

A549 Cells ◽

Hemorrhagic Fever ◽

Fever Virus ◽

World Health ◽

Small Interfering Rnas ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Antiviral Therapies

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of the World Health Organization, considering its potential to create a public health emergency and, more importantly, the absence of efficacious drugs and/or vaccines for treatment. The highly pathogenic characteristic of CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design and test siRNAs in vitro that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 h, nucleic acid from the supernatant was extracted for RT Droplet Digital PCR analysis. Among the investigated siRNAs we identified effective candidates against all three segments of the CCHF genome. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAs. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication in vitro. This promising result can be integrated into future anti-CCHFV therapy developments.

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Risk factors for Crimean-Congo hemorrhagic fever virus infection in Livestock in Pakistan

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2018.11.335 ◽

2019 ◽

Vol 79 ◽

pp. 137 ◽

Cited By ~ 1

Author(s):

K.K. Kasi ◽

M.A. Sas ◽

C. Sauter-Louis ◽

J.M. Gethmann ◽

M.H. Groschup ◽

...

Keyword(s):

Risk Factors ◽

Virus Infection ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus

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Induction of Caspase Activation and Cleavage of the Viral Nucleocapsid Protein in Different Cell Types during Crimean-Congo Hemorrhagic Fever Virus Infection

Journal of Biological Chemistry ◽

10.1074/jbc.m110.149369 ◽

2010 ◽

Vol 286 (5) ◽

pp. 3227-3234 ◽

Cited By ~ 44

Author(s):

Helen Karlberg ◽

Yee-Joo Tan ◽

Ali Mirazimi

Keyword(s):

Virus Infection ◽

Nucleocapsid Protein ◽

Hemorrhagic Fever ◽

Cell Types ◽

Fever Virus ◽

Caspase Activation ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Different Cell Types ◽

Viral Nucleocapsid

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Evaluation of Crimean-Congo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules

Antiviral Research ◽

10.1016/j.antiviral.2015.03.005 ◽

2015 ◽

Vol 118 ◽

pp. 75-81 ◽

Cited By ~ 25

Author(s):

O. Ferraris ◽

M. Moroso ◽

O. Pernet ◽

S. Emonet ◽

A. Ferrier Rembert ◽

...

Keyword(s):

Hemorrhagic Fever ◽

Fever Virus ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

In Vitro Inhibition

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Ultrastructural Features of Alkhumra Hemorrhagic Fever Virus Infection of Cells Under In Vivo and In Vitro Conditions

Vector-Borne and Zoonotic Diseases ◽

10.1089/vbz.2017.2194 ◽

2018 ◽

Vol 18 (2) ◽

pp. 108-113

Author(s):

Tariq A. Madani ◽

El-Tayb M.E. Abuelzein ◽

Huda Abu-Araki ◽

Soad S. Ali ◽

Sawsan M. Jalalah ◽

...

Keyword(s):

Virus Infection ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Hemorrhagic Fever Virus

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The Crimean-Congo Hemorrhagic Fever Virus NSm Protein Is Dispensable for Growth In Vitro and Disease in Ifnar-/- Mice

Microorganisms ◽

10.3390/microorganisms8050775 ◽

2020 ◽

Vol 8 (5) ◽

pp. 775 ◽

Cited By ~ 1

Author(s):

Stephen R. Welch ◽

Florine E. M. Scholte ◽

Jessica R. Spengler ◽

Jana M. Ritter ◽

JoAnn D. Coleman-McCray ◽

...

Keyword(s):

Clinical Signs ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Structural Proteins ◽

Glycoprotein Precursor ◽

Crimean Congo Hemorrhagic Fever ◽

Virus Attachment ◽

Hemorrhagic Fever Virus ◽

Endoproteolytic Cleavage

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tri-segmented, tick-borne nairovirus that causes disease of ranging severity in humans. The CCHFV M segment encodes a complex glycoprotein precursor (GPC) that undergoes extensive endoproteolytic cleavage, giving rise to two structural proteins (Gn and Gc) required for virus attachment and entry, and to multiple non-structural proteins (NSm, GP160, GP85, and GP38). The functions of these non-structural proteins remain largely unclear. Here, we investigate the role of NSm during infection by generating a recombinant CCHFV lacking the complete NSm domain (10200∆NSm) and observing CCHFV ∆NSm replication in cell lines and pathogenicity in Ifnar-/- mice. Our data demonstrate that the NSm domain is dispensable for viral replication in vitro, and, despite the delayed onset of clinical signs, CCHFV lacking this domain caused severe or lethal disease in infected mice.

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