Norovirus is a major cause of acute gastroenteritis worldwide, particularly in young children, and represents a significant public health concern. ZFP36L1, an RNA-binding protein, has demonstrated antiviral effects against several viruses, but its role in norovirus infection has not been previously studied. This study used murine norovirus 1 (MNV-1) as a model to investigate the antiviral role of ZFP36L1 against norovirus. The results show that overexpression of ZFP36L1 suppressed while knockdown of ZFP36L1 increased MNV-1 replication. MNV-1 infection induced autophagy, as indicated by increased levels of ATG13 and LC3-I to LC3-II conversion. Pharmacological modulation of autophagy-related pathways using rapamycin or 3-methyladenine was associated with changes in MNV-1 replication. ZFP36L1 overexpression reduced the expression of autophagy-related markers under basal conditions and following MNV-1 infection or rapamycin treatment indicating the ZFP36L1-mediated autophagy suppression contributed to a reduction in MNV-1 titer. ZFP36L1 overexpression led to reduced expression of several autophagy-related genes, including ATG13, Beclin-1, and Bcl-2, although the Beclin-1/Bcl-2 ratio remained unchanged. The decrease in ATG13 may be the reason for impaired autophagy and reduced autophagy may be one of the contributing factors to ZFP36L1-mediated norovirus suppression; however, other mechanisms such as direct interactions between ZFP36L1 and noroviral RNA still need to be investigated.
Bhowmik et al. (Tue,) studied this question.