Phosphatidylserine receptors are critical for lethal infection by Crimean-Congo hemorrhagic fever virus

Germline knockout of two phosphatidylserine receptors in mice completely protected against lethal Crimean-Congo hemorrhagic fever virus challenge, reducing viremia, replication, pathology, and inflammation to baseline.

• Why it matters: CCHFV causes severe, often fatal hemorrhagic disease with no approved countermeasures, and the field lacks validated host targets that block infection and downstream pathology.
• What they did: The study identified phosphatidylserine receptors AXL, TIM-1, and TIM-4 as critical entry host factors using cell lines and liver-derived primary cell cultures, then tested small-molecule and antibody PSR inhibitors.
• The result: In a murine lethal challenge model, individual PSR knockouts gave partial protection, while mice lacking two PSRs showed baseline levels of viral burden and liver/spleen pathology, supporting PSRs as antiviral targets.

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