Induction and Suppression of Innate Antiviral Responses by Hepatitis A Virus

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Hepatitis A virus (HAV) causes acute viral hepatitis via fecal-oral transmission.
• RNA viruses trigger innate immunity through pattern recognition receptors (PRRs), initiating antiviral responses like type 1 interferon (IFN-α/β) production.
• HAV has evolved immune evasion strategies to counteract host defenses.

Purpose of the Study:

• To review recent findings on host-HAV interactions.
• To focus on HAV's mechanisms for abrogating innate immune responses.

Main Methods:

• Review of scientific literature on HAV and innate immunity.
• Analysis of HAV's strategies to inhibit host antiviral signaling pathways.

Main Results:

• HAV proteases cleave crucial adaptor proteins: mitochondrial antiviral signaling protein (MAVS), TIR domain-containing adaptor inducing IFN-β (TRIF), and nuclear factor-κB (NF-κB) essential modulator (NEMO).
• Cleavage of these adaptors disrupts RIG-I-like receptor (RLR), TLR3, and NF-κB signaling pathways.
• These disruptions compromise the host's ability to mount an effective antiviral response, facilitating HAV propagation.

Conclusions:

• HAV actively antagonizes host antiviral immunity through protease-mediated cleavage of essential signaling adaptors.
• Understanding these immune evasion tactics is crucial for developing effective therapeutic strategies against Hepatitis A.