# LINC1467 Activates the IPO8–p65 Axis to Restrict Hand, Foot, and Mouth Disease Virus Replication

## TL;DR

This study identifies a non-coding RNA, LINC1467, that helps fight hand, foot, and mouth disease virus by boosting the immune response.

## Contribution

The study reveals a new mechanism where LINC1467 activates the IPO8–p65 axis to combat viral replication.

## Key findings

- LINC1467 is upregulated during HFMD-related virus infection and suppresses viral replication.
- LINC1467 forms a complex with IPO8 and p65 to promote NF-κB pathway activation and cytokine production.
- The antiviral role of LINC1467 was confirmed in a mouse model of viral infection.

## Abstract

Hand–foot–mouth disease (HFMD), primarily caused by human enteroviruses (EVs), poses a public health challenge, particularly among infants, due to a lack of effective therapies. Elucidating the molecular interplay between EVs and the host immune response is crucial for developing antiviral treatments. Recent studies have highlighted the significance of long non-coding RNAs (lncRNAs) in regulating host–pathogen interactions; however, the mechanisms of lncRNAs in EV infection remain poorly unexplored. Here, we identified a highly inducible nuclear lncRNA, LINC1467, that is upregulated in response to HFMD-related EV infection. Functional analyses revealed that LINC1467 suppresses viral replication. Mechanistically, LINC1467 interacts with nuclear import receptor Importin 8 (IPO8) to form the LINC1467/IPO8/p65 complex, facilitating the phosphorylation and nuclear translocation of p65, thus promoting the expression of pro-inflammatory cytokines and activating the NF-κB pathway. The antiviral function of LINC1467 was further validated in a mouse model of viral infection. These findings uncover a novel lncRNA-mediated regulatory mechanism in the innate immune response and highlight LINC1467 as a promising target for future antiviral strategies against HFMD-related EVs.