Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) promotes EIAV replication and infectivity

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Adenosine deaminases that act on RNA (ADARs) play complex roles in viral infections, with ADAR1 showing both antiviral and proviral activities.
• The interaction between ADAR1 and lentiviruses like Human Immunodeficiency Virus (HIV)-1 is variable and not fully understood.
• Equine infectious anemia virus (EIAV) is a lentivirus within the Retroviridae family, whose interaction with host factors like ADAR1 requires investigation.

Purpose of the Study:

• To investigate the role of equine ADAR1 (eADAR1) in the replication and infectivity of equine infectious anemia virus (EIAV).
• To determine if eADAR1 exhibits antiviral or proviral activity against EIAV.
• To elucidate the specific domains of eADAR1 involved in regulating EIAV.

Main Methods:

• Assessing the effect of eADAR1 expression on EIAV replication and viral protein production.
• Identifying the specific regions of eADAR1, particularly the RNA binding domain 1, responsible for modulating EIAV gene expression.
• Comparing the impact of eADAR1 on EIAV infectivity with that of APOBEC proteins.

Main Results:

• Equine ADAR1 (eADAR1) significantly promoted EIAV replication.
• Enhancement of viral protein expression was linked to the long terminal repeat (LTR) and Rev response element (RRE) regions of EIAV.
• The RNA binding domain 1 of eADAR1 was crucial for enhancing LTR-mediated gene expression.
• eADAR1 increased EIAV infectivity, contrasting with the known inhibitory effects of APOBEC proteins on lentiviruses.

Conclusions:

• Equine ADAR1 acts as a positive regulator and proviral factor for equine infectious anemia virus (EIAV).
• eADAR1 enhances EIAV replication and infectivity through mechanisms involving LTR and RRE.
• This finding contrasts with the typical antiviral roles observed for some RNA-editing enzymes in lentiviral infections.