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Mouse adenovirus type 1 replication in vitro is resistant to interferon
1Department of Genetics, University of Georgia, Athens, Georgia 30602, USA.
Abstract:
The effects of mouse interferon (IFN)-alpha/beta and recombinant IFN-gamma on mouse adenovirus type 1 (MAV-1) replication were investigated in single-cycle infectious virus yield reduction assays on mouse L929 cells. Viral yields at 3 days postinfection indicated that wt MAV-1 and pmE314, an early region 3 null mutant, were relatively insensitive to both IFN-alpha/beta and IFN-gamma, whereas early region 1A (E1A) mutants pmE109 (null), dlE105 (conserved region 1 deletion, CR1 Delta), dlE102 (CR2 Delta), and dlE106 (CR3 Delta) were sensitive. MAV-1 E1A that was inducibly expressed in mouse fibroblast 37.1 cells rescued vesicular stomatitis virus from the antiviral effect of IFN-alpha/beta but not from the antiviral effect of IFN-gamma. Interferon-inducible gene expression was reduced in 37.1 cells as compared to the parental 3T6 cell line. Steady-state levels of IFN-inducible gene mRNAs were also reduced in 3T6 cells infected with the wild-type virus and pmE314 but not in cells infected with pmE109. These results suggest that the MAV-1 E1A gene product is capable of interfering with the signaling pathways of both types of IFN, although modulation of IFN-alpha/beta antiviral activity was more pronounced.
Insights
Mouse adenovirus type 1 (MAV-1) early region 1A (E1A) mutants are sensitive to interferons (IFNs). MAV-1 E1A interferes with interferon signaling pathways, particularly modulating IFN-alpha/beta antiviral activity.
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.