MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain.

Area of Science:

• Immunology
• Neurovirology
• Molecular Biology

Background:

• Mucosa-associated lymphoid tissue lymphoma-membrane protein 1 (MALT1) is a key regulator of immune responses, involved in NF-κB signaling and gene expression.
• Deregulated MALT1 activity is linked to autoimmunity and cancer, making it a potential therapeutic target.
• The role of MALT1 in viral infections, particularly in the central nervous system, remains largely unexplored.

Purpose of the Study:

• To investigate the impact of MALT1 on the outcome of rabies virus infection in the central nervous system.
• To elucidate the role of MALT1-mediated immune responses in controlling viral pathogenesis.

Main Methods:

• Infection of MALT1-deficient (MALT1^-/-) and wild-type (MALT1^+/+) mice with an attenuated Evelyn-Rotnycki-Abelseth (ERA) rabies virus strain.
• Assessment of clinical signs, survival rates, inflammatory gene expression, immune cell infiltration and activation, and virus-neutralizing antibody production.
• Evaluation of MALT1 protease inhibitor (mepazine) treatment in wild-type mice.

Main Results:

• MALT1^-/- mice exhibited increased susceptibility to ERA virus infection, developing severe disease and reduced survival compared to wild-type mice.
• MALT1 deficiency led to decreased early inflammatory responses and T cell activation following infection.
• MALT1^-/- mice failed to produce virus-neutralizing antibodies, and MALT1 inhibition exacerbated rabies virus virulence.

Conclusions:

• MALT1 plays a critical role in controlling the virulence of attenuated rabies virus in the brain.
• Early MALT1-dependent inflammation and T cell activation are essential for effective viral clearance and host survival.
• These findings highlight MALT1 as a potential therapeutic target for rabies virus infections.