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Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein

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Abstract
The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junin (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.
Keywords
ARGENTINE HEMORRHAGIC-FEVER, INCLUSION-BODY DISEASE, LYMPHOCYTIC CHORIOMENINGITIS VIRUS, LIVE-ATTENUATED VACCINE, ARENAVIRUS INFECTIONS, CANDID NUMBER-1, LASSA FEVER, IN-VITRO, GLYCOPROTEIN, RECEPTOR

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Citation

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MLA
Linero, Florencia, Claudia Sepúlveda, Ioanna Christopoulou, et al. “Neutralization of Junín Virus by Single Domain Antibodies Targeted Against the Nucleoprotein.” SCIENTIFIC REPORTS 8 (2018): n. pag. Print.
APA
Linero, F., Sepúlveda, C., Christopoulou, I., Hulpiau, P., Scolaro, L., & Saelens, X. (2018). Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein. SCIENTIFIC REPORTS, 8.
Chicago author-date
Linero, Florencia, Claudia Sepúlveda, Ioanna Christopoulou, Paco Hulpiau, Luis Scolaro, and Xavier Saelens. 2018. “Neutralization of Junín Virus by Single Domain Antibodies Targeted Against the Nucleoprotein.” Scientific Reports 8.
Chicago author-date (all authors)
Linero, Florencia, Claudia Sepúlveda, Ioanna Christopoulou, Paco Hulpiau, Luis Scolaro, and Xavier Saelens. 2018. “Neutralization of Junín Virus by Single Domain Antibodies Targeted Against the Nucleoprotein.” Scientific Reports 8.
Vancouver
1.
Linero F, Sepúlveda C, Christopoulou I, Hulpiau P, Scolaro L, Saelens X. Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein. SCIENTIFIC REPORTS. 2018;8.
IEEE
[1]
F. Linero, C. Sepúlveda, I. Christopoulou, P. Hulpiau, L. Scolaro, and X. Saelens, “Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein,” SCIENTIFIC REPORTS, vol. 8, 2018.
@article{8583897,
  abstract     = {The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junin (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.},
  articleno    = {11451},
  author       = {Linero, Florencia and Sepúlveda, Claudia and Christopoulou, Ioanna and Hulpiau, Paco and Scolaro, Luis and Saelens, Xavier},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keywords     = {ARGENTINE HEMORRHAGIC-FEVER,INCLUSION-BODY DISEASE,LYMPHOCYTIC CHORIOMENINGITIS VIRUS,LIVE-ATTENUATED VACCINE,ARENAVIRUS INFECTIONS,CANDID NUMBER-1,LASSA FEVER,IN-VITRO,GLYCOPROTEIN,RECEPTOR},
  language     = {eng},
  pages        = {17},
  title        = {Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein},
  url          = {http://dx.doi.org/10.1038/s41598-018-29508-1},
  volume       = {8},
  year         = {2018},
}

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