ITAF₄₅ is a pervasive trans-acting factor for picornavirus Type II IRES elements

Area of Science:

• Virology
• Molecular Biology
• Biochemistry

Background:

• Picornaviruses, lacking a 5' cap, use internal ribosome entry sites (IRES) for translation.
• IRES activity is modulated by host proteins known as IRES trans-acting factors (ITAFs).
• ITAF45 was previously considered specific to foot-and-mouth disease virus (FMDV) infection.

Purpose of the Study:

• To investigate the broader role of ITAF45 in Type II IRES-containing picornavirus replication.
• To determine if ITAF45 is a general host factor for various picornaviruses.

Main Methods:

• CRISPR/Cas9 gene editing to knockout ITAF45 in human cell lines.
• Infection assays with FMDV, encephalomyocarditis virus (EMCV), Theiler's murine encephalomyelitis virus (TMEV), and equine rhinitis A virus (ERAV).
• Analysis of ITAF45's role in enhancing translation initiation on Type II IRES elements.

Main Results:

• CRISPR/Cas9 knockout of ITAF45 conferred resistance to FMDV, EMCV, TMEV, and ERAV infection.
• ITAF45 was confirmed as a pervasive host factor for picornaviruses utilizing Type II IRES.
• The C-terminal lysine-rich region of ITAF45 mediates viral RNA binding and enhances translation initiation.

Conclusions:

• ITAF45 plays a significant, previously underestimated role in the replication of diverse Type II IRES picornaviruses.
• These findings challenge prior assumptions about ITAF45's restricted function.
• ITAF45 represents a promising pan-viral therapeutic target against animal and emerging human cardioviruses.