# Lassa Virus Infection of Primary Human Airway Epithelial Cells

## TL;DR

This study shows that Lassa virus can infect human airway cells, replicates efficiently, and may spread through respiratory secretions.

## Contribution

The study demonstrates productive Lassa virus replication in primary human airway epithelial cells and reveals apical virus shedding and interferon responses.

## Key findings

- HAECs are permissive to LASV infection and support productive replication.
- Progeny virus is predominantly released apically, suggesting transmission via airway secretions.
- LASV induces a strong type III interferon response in infected HAECs.

## Abstract

Lassa mammarenavirus (LASV), a member of the family Arenaviridae, is a highly pathogenic virus capable of causing severe systemic infections in humans. The primary host reservoir is the Natal multimammate mouse (Mastomys natalensis), with human infections typically occurring through mucosal exposure to virus-containing aerosols from rodent excretions. To better understand the molecular mechanisms underlying LASV replication in the respiratory tract, we utilized differentiated primary human airway epithelial cells (HAECs) grown under air–liquid interface conditions, closely mimicking the bronchial epithelium in vivo. Our findings demonstrate that HAECs are permissive to LASV infection and support productive virus replication. While LASV entry into polarized HAECs occurred through both apical and basolateral surfaces, progeny virus particles were predominantly released from the apical surface, consistent with an intrinsic apical localization of the envelope glycoprotein GP. This suggests that apical virus shedding from infected bronchial epithelia may facilitate LASV transmission via airway secretions. Notably, limited basolateral release at later stages of infection was associated with LASV-induced rearrangement of the actin cytoskeleton, resulting in compromised epithelial barrier integrity. Finally, we demonstrate that LASV-infected HAECs exhibited a pronounced type III interferon response. A detailed understanding of LASV replication and host epithelial responses in the respiratory tract could facilitate the development of targeted future therapeutics.