The ring finger protein 213 gene (Rnf213) contributes to Rift Valley fever resistance in mice

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Rift Valley fever (RVF) is an emerging viral zoonosis affecting humans and ruminants.
• Previous studies identified a susceptibility locus for RVF on mouse Chromosome 11.
• RNF213 is a candidate gene within this locus, previously linked to Moyamoya disease.

Purpose of the Study:

• To investigate the role of Rnf213 in RVF susceptibility.
• To determine if Rnf213 influences host resistance to viral infections.

Main Methods:

• Generation of Rnf213-deficient mice using CRISPR/Cas9 technology on a C57BL/6J background.
• Infection of Rnf213-deficient and control mice with RVF virus.
• Assessment of RVF susceptibility through survival analysis.

Main Results:

• Rnf213-deficient mice exhibited significantly increased susceptibility to RVF compared to control mice.
• Average survival time post-RVF infection was reduced from 7 days in controls to 4 days in deficient mice.
• Inactivation of Rnf213 in mice led to mild neovascularization anomalies, distinct from its known role in Moyamoya disease.

Conclusions:

• The Rnf213 gene plays a crucial role in host resistance to Rift Valley fever virus.
• This study provides the first evidence linking Rnf213 to the regulation of infectious disease resistance.
• RNF213 may represent a novel therapeutic target for managing RVF and potentially other infectious diseases.