N-terminal acetyltransferase 6 facilitates enterovirus 71 replication by regulating PI4KB expression and replication...

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Enterovirus 71 (EV71) causes severe hand, foot, and mouth disease in children, with limited treatment options.
• Identifying host factors is key to developing antiviral strategies against EV71.

Purpose of the Study:

• To identify novel host factors essential for EV71 infection.
• To elucidate the mechanism by which these factors support viral replication.

Main Methods:

• Genome-wide CRISPR/Cas9 screening to identify host factors.
• Assays to assess viral replication, Golgi integrity, and protein interactions.
• Analysis of phosphatidylinositol 4-kinase IIIβ (PI4KB) and acyl-coenzyme A binding domain containing 3 (ACBD3) involvement.

Main Results:

• N-terminal acetyltransferase 6 (NAT6) was identified as an essential host factor for EV71 replication.
• NAT6 facilitates viral replication via its acetyltransferase activity, supporting Golgi integrity and replication organelle biogenesis.
• NAT6 stabilizes ACBD3, enhances PI4KB expression and PI4P production, crucial for enterovirus replication.

Conclusions:

• NAT6 is a novel host factor supporting EV71 infection by maintaining Golgi and replication organelle stability.
• NAT6's role in stabilizing ACBD3 and influencing PI4KB/PI4P pathways provides new insights into enterovirus replication mechanisms.
• NAT6 may be a potential pan-enterovirus target, as it's also required for Echovirus 7 and coxsackievirus B5.