# Characterization of conserved residues in the mammarenavirus matrix protein Z using novel Lassa virus life cycle modelling assays

## TL;DR

Researchers developed a new system to study Lassa virus life cycle and identified key amino acids in the virus's matrix protein that are crucial for its replication and interactions.

## Contribution

A novel trVLP system was developed to model the LASV life cycle outside high-containment labs, revealing essential conserved residues in the Z protein.

## Key findings

- Residues L71 and P72 are essential for Z protein's role in inhibiting viral RNA synthesis.
- Residues L71-T73 mediate interaction of Z with the viral nucleoprotein (NP), supported by residue G2.

## Abstract

Lassa virus (LASV) is the causative agent of Lassa fever, which causes thousands of deaths every year within the endemic regions of West Africa. Despite its discovery over half a century ago, our knowledge regarding basic steps in the LASV life cycle remains limited. In order to simplify studying basic principles of the LASV life cycle, we developed a novel transcription- and replication-competent virus-like particle (trVLP) system that can model the whole virus life cycle using only authentic LASV components but without the need for a maximum containment laboratory. As a proof-of-concept we used this system, together with classical minigenome systems, to determine the functional contributions of highly conserved amino acids within the mammarenavirus matrix protein Z. We could demonstrate that residues L71 and P72 are essential for the role of Z in inhibiting viral RNA synthesis, with residues R16, D22, K68 and T73 also contributing to this function. Additionally, we showed that L71-T73 mediate interaction of Z with the viral nucleoprotein (NP), which is also supported by residue G2. Given the critical role of these interactions in the virus life cycle, understanding these amino acids’ functions will help to define potential targets for the development of urgently needed countermeasures.

The online version contains supplementary material available at 10.1038/s41598-026-40023-6.