Effective Interferon Lambda Treatment Regimen To Control Lethal MERS-CoV Infection in Mice

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Broad-spectrum antivirals are crucial for emerging human coronavirus (hCoV) infections.
• Existing antivirals have limited efficacy due to narrow therapeutic windows.
• Type-I interferons (IFN-Is) have side effects and can cause inflammation, limiting clinical use.

Purpose of the Study:

• To evaluate the prophylactic and therapeutic efficacy of interferon-lambda (IFN-λ) against hCoV infections.
• To determine an effective treatment regimen for IFN-λ in MERS-CoV infection.
• To compare IFN-λ's efficacy with IFN-I in inducing antiviral responses.

Main Methods:

• Treatment of human primary airway epithelial cells and mice with IFN-λ and IFN-α.
• Assessment of IFN-stimulated gene (ISG) expression.
• Evaluation of protection against Middle East respiratory syndrome coronavirus (MERS-CoV) infection.
• Measurement of lung viral titers and inflammatory cytokine levels.

Main Results:

• A two-dose IFN-λ regimen induced higher ISG expression in cells compared to IFN-α.
• Mice treated with two doses of IFN-λ showed better protection than those receiving a single dose.
• A combination of prophylactic and delayed therapeutic IFN-λ regimens completely protected mice from lethal MERS-CoV infection.
• IFN-λ treatment significantly reduced viral titers, inflammatory cytokines, and lung inflammation.

Conclusions:

• IFN-λ is a potent antiviral agent against MERS-CoV with a favorable safety profile.
• An effective regimen involves a combination of prophylactic and delayed therapeutic administration of IFN-λ.
• IFN-λ holds potential for treating hCoV and other viral lung infections.