Coxsackievirus counters the host innate immune response by blocking type III interferon expression

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Type I interferons (IFNs) are crucial for antiviral immunity against enteroviruses.
• Enteroviruses, including Coxsackie B viruses (CVBs), possess mechanisms to counteract type I IFN responses.
• Type III IFNs (IFN-λs) show promise in controlling enteric viral infections, but their evasion by CVBs is unstudied.

Purpose of the Study:

• To investigate whether Coxsackie B viruses (CVBs) evade type III IFN responses.
• To elucidate the mechanisms by which CVBs might interfere with type III IFN production.
• To understand the role of viral proteases in subverting host antiviral pathways.

Main Methods:

• Virus infection studies using CVBs.
• Administration of poly I:C (a dsRNA mimic) to stimulate IFN pathways.
• Analysis of cellular protein expression, including signal transduction proteins (TRIF, IPS1) and IRF-3 phosphorylation.
• Incubation of cellular protein extracts with recombinant viral protease (2Apro).

Main Results:

• CVBs were found to inhibit both TLR3- and MDA5/RIG-I-mediated type III IFN expression.
• Infection led to reduced levels of TRIF and IPS1, and lack of IRF-3 hyperphosphorylation.
• Viral protease 2Apro was implicated in cleaving TRIF and IPS1, suggesting a key role in immune evasion.
• CVBs block multiple intracellular viral recognition pathways essential for both type I and III IFN production.

Conclusions:

• CVBs actively block the expression of type III IFNs.
• The mechanism of type III IFN evasion by CVBs is similar to that used against type I IFNs.
• CVBs employ a multi-pronged strategy, targeting numerous host immune pathways for replication and spread.