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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月18日

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  • Claudia Bastl,
  • Barbara Posch,
  • Madita Kudla,
  • Juliette Dupré,
  • Marine Noël Klamke,
  • Anne Leske,
  • Kyle Warren Shifflett,
  • Cedric Rajes,
  • Allison Groseth,
  • Thomas Hoenen,
  • Lisa Wendt

摘要

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.