Enterovirus 71 (EV71) is one of the major pathogens causing
hand, foot, and mouth disease in children under 5 years old, which can result in severe neurological complications and even death. Due to limited treatments for EV71
infection, the identification of novel host factors and elucidation of mechanisms involved will help to counter this
viral infection.
N-terminal acetyltransferase 6 (NAT6) was identified as an essential host factor for EV71
infection with genome-wide CRISPR/Cas9 screening. NAT6 facilitates EV71 viral replication depending on its
acetyltransferase activity but has little effect on viral release. In addition, NAT6 is also required for Echovirus 7 and coxsackievirus B5
infection, suggesting it might be a pan-enterovirus host factor. We further demonstrated that NAT6 is required for Golgi integrity and viral replication organelle (RO) biogenesis. NAT6 knockout significantly inhibited
phosphatidylinositol 4-kinase IIIβ (PI4KB) expression and PI4P production, both of which are key host factors for
enterovirus infection and RO biogenesis. Further mechanism studies confirmed that NAT6 formed a complex with its substrate actin and one of the PI4KB recruiters-
acyl-coenzyme A binding domain containing 3 (ACBD3). Through modulating actin dynamics, NAT6 maintained the integrity of the Golgi and the stability of ACBD3, thereby enhancing EV71
infection. Collectively, these results uncovered a novel mechanism of N-
acetyltransferase supporting EV71
infection.IMPORTANCEEnterovirus 71 (EV71) is an important pathogen for children under the age of five, and currently, no effective treatment is available. Elucidating the mechanism of novel host factors supporting
viral infection will reveal potential
antiviral targets and aid
antiviral development. Here, we demonstrated that a novel N-
acetyltransferase, NAT6, is an essential host factor for EV71 replication. NAT6 could promote viral replication organelle (RO) formation to enhance viral replication. The formation of enterovirus ROs requires numerous host factors, including
acyl-coenzyme A binding domain containing 3 (ACBD3) and
phosphatidylinositol 4-kinase IIIβ (PI4KB). NAT6 could stabilize the PI4KB recruiter, ACBD3, by inhibiting the autophagy degradation pathway. This study provides a fresh insight into the relationship between N-
acetyltransferase and
viral infection.