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Article
| Open Access
Rapid protection induced by a single-shot Lassa vaccine in male cynomolgus monkeys
Lassa virus vaccination is impeded by the limited capacity of vaccine candidates to induce rapid protection. In this study, the authors found that a single shot of a measles-based Lassa vaccine protected nonhuman primates 16 or 8 days after vaccination.
- Mathieu Mateo
- , Stéphanie Reynard
- & Sylvain Baize
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Article
| Open Access
Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
Five New World mammarenaviruses (NWMs) enter cells via binding to human transferrin receptor 1 (hTfR1). Here, Hickerson et al. show that hTfR1 targeting antibodies partially protect hTfR1-transgenic mice from lethal NWM challenge via competition of anti-hTfR1 antibody and viral glycoprotein for hTfR1.
- Brady T. Hickerson
- , Tracy R. Daniels-Wells
- & Brian B. Gowen
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Article
| Open Access
Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity
The L protein of segmented, negative strand RNA viruses contains the RNA-dependent RNA polymerase essential for virus amplification. Here, the authors report cryoEM structures of the Lassa virus L protein in active, RNA-bound states, and provide mechanistic insights.
- Tomas Kouba
- , Dominik Vogel
- & Stephen Cusack
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Article
| Open Access
Structure of Machupo virus polymerase in complex with matrix protein Z
The RNA polymerase L of arenaviruses is of interest for drug design and its activity is inhibited by the matrix protein Z. Here, the authors present the cryo-EM structure of the Machupo virus polymerase L in complex with matrix protein Z and discuss the inhibitory mechanism.
- Jun Ma
- , Shuangyue Zhang
- & Xinzheng Zhang
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Article
| Open Access
Structural basis for recognition and regulation of arenavirus polymerase L by Z protein
Junin virus (JUNV) causes Argentine hemorrhagic fever and encodes the large protein (L) of the RNA dependent RNA polymerase (RdRp) and its regulator, the matrix zinc-binding protein (Z). Here, the authors present the 3.54 Å cryo-EM structure of the complex of JUNV L with Z, and they propose a model of how JUNV L is regulated by Z during the viral life cycle and RNA synthesis.
- Huiling Kang
- , Jingyuan Cong
- & Zihe Rao
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Article
| Open Access
Rational design of universal immunotherapy for TfR1-tropic arenaviruses
New World arenaviruses utilize the cellular transferrin receptor 1 (TfR1) to enter host cells. Here, the authors develop a TfR1-mimetic immunoadhesin, Arenacept, that targets viral spike complexes and exerts effective pan-reactive neutralization against pathogenic mammarenaviruses.
- Hadas Cohen-Dvashi
- , Ron Amon
- & Ron Diskin
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Article
| Open Access
Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses
The five known New World hemorrhagic fever arenaviruses use the same entry receptor, but their viral glycoproteins are markedly different. Here, the authors isolate monoclonal antibodies from a Junin virus vaccinated person that cross-neutralize Machupo virus and identify a conserved epitope in the receptor-binding domain.
- Lars E. Clark
- , Selma Mahmutovic
- & Jonathan Abraham
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Article
| Open Access
Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression
Viruses are promising anti-tumour therapeutics due to induction of an immune response and/or oncolytic activity. Here, Kalkavanet al. show that LCMV replicates in tumour cells, without inducing cell lysis, and that its anti-tumour activity is largely mediated by recruitment of interferon-producing monocytes.
- Halime Kalkavan
- , Piyush Sharma
- & Karl S. Lang
A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection