Non-neutralizing antibody responses control acute Crimean-Congo hemorrhagic fever virus infection in naïve mice
- 1Laboratory of Virology, Rocky Mountain Laboratories, NIH/NIAID, Hamilton, Montana, USA
- 2Laboratory of Viral Zoonoses, Integrated Research Facility Frederick, NIH/NIAID, Frederick, Maryland, USA
Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of a sometimes-severe viral hemorrhagic fever, CCHF. Severe cases of CCHF often have little-to-no CCHFV-specific antibody responses prior to death. However, it is unclear if the failure to mount an antibody response is the cause of a poor outcome or a correlate of a failed host response. Here, we used a mouse-adapted strain of CCHFV (MA-CCHFV) to investigate the requirement of humoral immunity in control of acute CCHFV infection in immunocompetent mice. We found that mice infected with MA-CCHFV develop a rapid non-neutralizing antibody response, consistent with humans infected with CCHFV. Further, we found that the absence of humoral immunity in male but not female mice resulted in near-uniform mortality. Lastly, we determined that complement but not activating Fc-receptors nor the cytoplasmic Fc-receptor tripartite motif containing protein 21 contributed to antibody-mediated control of MA-CCHFV infection. Together, our findings identify rapid humoral immune responses as a critical component of the host response to acute CCHFV infection in naive hosts.
IMPORTANCE: Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of a serious viral hemorrhagic fever in humans. Severe disease and poor outcomes are correlated with little-to-no CCHFV-specific antibody. However, it is unknown if the lack of CCHFV-specific antibody is a direct cause or merely a correlate of a poor outcome. Here, we investigated the contribution of humoral immunity in control of acute CCHFV infection in naive immunocompetent mice. We found that mice develop a rapid, non-neutralizing antibody response that is crucial for control of the acute infection. Further, we found that loss of complement but not activating Fc receptors or the cytoplasmic Fc receptor TRIM21 worsened disease. Together, our findings suggest that lack of CCHFV-specific antibody responses may directly contribute to poor outcomes in CCHFV-infected humans.
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BibTeX
@article{meadewhite2026nonneutralizing,
title = {{Non-neutralizing antibody responses control acute Crimean-Congo hemorrhagic fever virus infection in naïve mice}},
author = {Kimberly Meade-White and Shanna S. Brown and Samantha Ertl and Natalie McCarthy and Thomas Tipih and Heinz Feldmann and David W. Hawman},
journal = {Journal of Virology},
year = {2026},
month = sep,
doi = {10.1128/jvi.00987-26},
url = {https://doi.org/10.1128/jvi.00987-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Non-neutralizing antibody responses control acute Crimean-Congo hemorrhagic fever virus infection in naïve mice
AU - Kimberly Meade-White
AU - Shanna S. Brown
AU - Samantha Ertl
AU - Natalie McCarthy
AU - Thomas Tipih
AU - Heinz Feldmann
AU - David W. Hawman
PY - 2026
DA - 2026/09/14
JO - Journal of Virology
DO - 10.1128/jvi.00987-26
UR - https://doi.org/10.1128/jvi.00987-26
AB - Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of a sometimes-severe viral hemorrhagic fever, CCHF. Severe cases of CCHF often have little-to-no CCHFV-specific antibody responses prior to death. However, it is unclear if the failure to mount an antibody response is the cause of a poor outcome or a correlate of a failed host response. Here, we used a mouse-adapted strain of CCHFV (MA-CCHFV) to investigate the requirement of humoral immunity in control of acute CCHFV infection in immunocompetent mice. We found that mice infected with MA-CCHFV develop a rapid non-neutralizing antibody response, consistent with humans infected with CCHFV. Further, we found that the absence of humoral immunity in male but not female mice resulted in near-uniform mortality. Lastly, we determined that complement but not activating Fc-receptors nor the cytoplasmic Fc-receptor tripartite motif containing protein 21 contributed to antibody-mediated control of MA-CCHFV infection. Together, our findings identify rapid humoral immune responses as a critical component of the host response to acute CCHFV infection in naive hosts. IMPORTANCE: Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of a serious viral hemorrhagic fever in humans. Severe disease and poor outcomes are correlated with little-to-no CCHFV-specific antibody. However, it is unknown if the lack of CCHFV-specific antibody is a direct cause or merely a correlate of a poor outcome. Here, we investigated the contribution of humoral immunity in control of acute CCHFV infection in naive immunocompetent mice. We found that mice develop a rapid, non-neutralizing antibody response that is crucial for control of the acute infection. Further, we found that loss of complement but not activating Fc receptors or the cytoplasmic Fc receptor TRIM21 worsened disease. Together, our findings suggest that lack of CCHFV-specific antibody responses may directly contribute to poor outcomes in CCHFV-infected humans.
SN - 0022-538X
SN - 1098-5514
ER -