Mouse adenovirus type 1 replication in vitro is resistant to interferon

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Interferons (IFNs) are crucial cytokines in antiviral defense.
• Mouse adenovirus type 1 (MAV-1) is a model virus for studying adenovirus biology.
• The role of MAV-1 early region 1A (E1A) in interferon response modulation is not fully understood.

Purpose of the Study:

• To investigate the effects of type I (IFN-alpha/beta) and type II (IFN-gamma) interferons on MAV-1 replication.
• To determine the role of MAV-1 E1A in interfering with interferon signaling pathways.

Main Methods:

• Single-cycle infectious virus yield reduction assays were performed on mouse L929 cells.
• Replication of wild-type MAV-1 and various E1A mutants was assessed in the presence of IFNs.
• Inducible expression of MAV-1 E1A was used to rescue virus from IFN-mediated antiviral effects.
• Interferon-inducible gene expression and mRNA levels were analyzed.

Main Results:

• Wild-type MAV-1 and an E3 mutant (pmE314) were relatively insensitive to both IFN-alpha/beta and IFN-gamma.
• MAV-1 E1A mutants (pmE109, dlE105, dlE102, dlE106) were sensitive to IFNs.
• Exogenous MAV-1 E1A expression rescued vesicular stomatitis virus from IFN-alpha/beta but not IFN-gamma antiviral effects.
• Interferon-inducible gene expression and mRNA levels were reduced in cells expressing MAV-1 E1A.

Conclusions:

• The MAV-1 E1A gene product interferes with both IFN-alpha/beta and IFN-gamma signaling pathways.
• The modulation of IFN-alpha/beta antiviral activity by MAV-1 E1A is more pronounced.
• MAV-1 E1A plays a significant role in antagonizing the host interferon response.