Soluble MFGE8 mediates cell entry of Crimean-Congo hemorrhagic fever virus

CCHFV causes severe hemorrhagic fever outbreaks, with a mortality rate of up to 40%. Countries generally list CCHFV as one of the pathogens that requires the highest biosafety level 4 (BSL-4) of containment, which hinders the study of its cell biology and pathogenesis. LDLR was recently identified as a receptor for CCHFV, but other receptors or co-factors remain to be explored. We perform genome-wide CRISPR screens using a safe replication-competent CCHFV pseudovirus and identify a secretory MFGE8 protein that functions as an entry mediator by binding to both the Gc protein and PtdSer on the viral envelope and to the integrins on the cells. Cell entry mediated by a soluble protein may greatly expand the tissue tropism, and the strategies developed to disturb the interaction of MFGE8 with virions or with integrins may help to mitigate the fatal disease induced by CCHFV.

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Publication Details

Journal
mBio
Published
2025-08-25
DOI
https://doi.org/10.1128/mbio.01617-25
Primary Topic
Mosquito-borne diseases and control
Type
article
Field-Weighted Citation Impact
0.00

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article

Soluble MFGE8 mediates cell entry of Crimean-Congo hemorrhagic fever virus

Sheng Cao, Manli Wang, Lulu Yang, Zhisheng Xu et al.
mBio
Mosquito-borne diseases and control
article

Soluble MFGE8 mediates cell entry of Crimean-Congo hemorrhagic fever virus

Sheng Cao, Manli Wang, Lulu Yang, Zhisheng Xu, Ziqiao Wang, Xue Ma, Yanlong Ma, Zhichao Gao, Wen-Tian Du, Yan‐Yi Wang, Qian Li, Rong Zhang, Fei Feng, Ruoting Zhan, Sicheng Tian, Yan Fu
article en

Abstract

CCHFV causes severe hemorrhagic fever outbreaks, with a mortality rate of up to 40%. Countries generally list CCHFV as one of the pathogens that requires the highest biosafety level 4 (BSL-4) of containment, which hinders the study of its cell biology and pathogenesis. LDLR was recently identified as a receptor for CCHFV, but other receptors or co-factors remain to be explored. We perform genome-wide CRISPR screens using a safe replication-competent CCHFV pseudovirus and identify a secretory MFGE8 protein that functions as an entry mediator by binding to both the Gc protein and PtdSer on the viral envelope and to the integrins on the cells. Cell entry mediated by a soluble protein may greatly expand the tissue tropism, and the strategies developed to disturb the interaction of MFGE8 with virions or with integrins may help to mitigate the fatal disease induced by CCHFV.

mBioVol. 16(10)
Shanghai Medical College of Fudan University (CN), Wuhan Institute of Virology (CN)
Program of Shanghai Academic Research Leader
Openalex Percentile: Top 70%
Mosquito-borne diseases and control
DOIOpen Access PDFOpenAlex
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