A Substitution in the Transmembrane Region of the Glycoprotein Leads to an Unstable Attenuation of Machupo Virus

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2014 Jul 18

PMID 25031335

Citations 12

Authors

Michael Patterson

Takaaki Koma

Alexey Seregin

Cheng Huang

Milagros Miller

Jennifer Smith

Nadezhda Yun

Jeanon Smith

Slobodan Paessler

Affiliations

Soon will be listed here.

Abstract

Machupo virus (MACV) is the etiologic agent of Bolivian hemorrhagic fever (BHF). Utilizing a reverse-genetics system recently developed, we report the rescue of a rationally modified recombinant MACV containing a single mutation in the transmembrane region of the glycoprotein. Following challenge of susceptible mice, we identified a significant reduction in virulence in the novel virus. We also identified an instability leading to reversion of the single mutation to a wild-type genotype.

Citing Articles

Development of reverse genetic tools to study Chapare and Machupo viruses.

Jain S, Shrivastava-Ranjan P, Flint M, Montgomery J, Spiropoulou C, Albarino C Virology. 2023; 588:109888.

PMID: 37774602 PMC: 11539271. DOI: 10.1016/j.virol.2023.109888.

Hemorrhagic fever viruses: Pathogenesis, therapeutics, and emerging and re-emerging potential.

Florez-Alvarez L, de Souza E, Botosso V, de Oliveira D, Ho P, Taborda C Front Microbiol. 2022; 13:1040093.

PMID: 36386719 PMC: 9640979. DOI: 10.3389/fmicb.2022.1040093.

Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever.

Mantlo E, Maruyama J, Manning J, Wanninger T, Huang C, Smith J J Virol. 2022; 96(8):e0020922.

PMID: 35343792 PMC: 9044957. DOI: 10.1128/jvi.00209-22.

Glycoprotein N-linked glycans play a critical role in arenavirus pathogenicity.

Koma T, Huang C, Coscia A, Hallam S, Manning J, Maruyama J PLoS Pathog. 2021; 17(3):e1009356.

PMID: 33647064 PMC: 7951981. DOI: 10.1371/journal.ppat.1009356.

Bivalent Junin & Machupo experimental vaccine based on alphavirus RNA replicon vector.

Johnson D, Jokinen J, Wang M, Pfeffer T, Tretyakova I, Carrion Jr R Vaccine. 2020; 38(14):2949-2959.

PMID: 32111526 PMC: 7112472. DOI: 10.1016/j.vaccine.2020.02.053.

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