An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection

Scientific Reports
Joseph W GoldenJay W Hooper

Abstract

Machupo virus (MACV) is a New World (NW) arenavirus and causative agent of Bolivian hemorrhagic fever (HF). Here, we identified a variant of MACV strain Carvallo termed Car91 that was attenuated in guinea pigs. Infection of guinea pigs with an earlier passage of Carvallo, termed Car68, resulted in a lethal disease with a 63% mortality rate. Sequencing analysis revealed that compared to Car68, Car91 had a 35 nucleotide (nt) deletion and a point mutation within the L-segment intergenic region (IGR), and three silent changes in the polymerase gene that did not impact amino acid coding. No changes were found on the S-segment. Because it was apathogenic, we determined if Car91 could protect guinea pigs against Guanarito virus (GTOV), a distantly related NW arenavirus. While naïve animals succumbed to GTOV infection, 88% of the Car91-exposed guinea pigs were protected. These findings indicate that attenuated MACV vaccines can provide heterologous protection against NW arenaviruses. The disruption in the L-segment IGR, including a single point mutant and 35 nt partial deletion, were the only major variance detected between virulent and avirulent isolates, implicating its role in attenuation. Overall, our data support the development o...Continue Reading

References

May 1, 1978·Journal of Virology·A C VezzaD H Bishop
Feb 1, 1989·Journal of Medical Virology·N A CandurraC E Coto
Jan 1, 1988·Journal of Medical Virology·C B DejeanA R Teyssié
Mar 1, 1986·Antimicrobial Agents and Chemotherapy·R H KenyonC J Peters
Jun 1, 1987·Journal of Clinical Pathology·D F NixonR P Eglin
Feb 1, 1966·The American Journal of Medicine·B J StinebaughE De Alba
Jun 1, 1974·American Journal of Epidemiology·C J PetersP A Webb
Mar 1, 1969·Proceedings of the Society for Experimental Biology and Medicine·P A WebbR B Mackenzie
Feb 1, 1982·Infection and Immunity·M C WeissenbacherM J Frigerio
Jul 1, 1983·The American Journal of Tropical Medicine and Hygiene·S R SamoilovichM C Weissenbacher
Apr 1, 1994·The American Journal of Tropical Medicine and Hygiene·R B TeshR E Shope
Mar 1, 1993·The American Journal of Tropical Medicine and Hygiene·K T McKeeB G Mahlandt
Feb 18, 1998·The Journal of Infectious Diseases·J I MaizteguiC J Peters
Apr 18, 2000·The Journal of General Virology·N LópezM T Franze-Fernández
Aug 25, 2000·MMWR. Morbidity and Mortality Weekly Report·UNKNOWN Centers for Disease Control and Prevention (CDC)
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·O LenzW Garten
Mar 5, 2003·Antiviral Research·Rémi N Charrel, Xavier de Lamballerie
Jul 31, 2003·Thrombosis and Haemostasis·Ricardo Martin GomezMirta Schattner
Jan 1, 1965·Proceedings of the Society for Experimental Biology and Medicine·K M JOHNSONH K BEYE
Oct 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Mar PerezJuan C de la Torre
Jan 9, 2008·BMC Genomics·Appolinaire DjikengDavid J Spiro
Dec 2, 2008·Virus Research·Maria N B CajimatCharles F Fulhorst
Sep 15, 2009·Veterinary Microbiology·R N Charrel, X de Lamballerie
Dec 31, 2009·Reviews in Medical Virology·A C Marriott, N J Dimmock
Oct 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Philip J KranzuschSean P J Whelan
Feb 1, 2011·Bioinformatics·Robert Schmieder, Robert Edwards
May 26, 2012·PLoS Neglected Tropical Diseases·Cheng HuangSlobodan Paessler
Nov 6, 2012·Annual Review of Pathology·Slobodan Paessler, David H Walker
Jan 16, 2015·Journal of Virology·Benson Yee Hin ChengLuis Martínez-Sobrido
Jul 4, 2015·Veterinary Pathology·T M BellK A Cashman
Aug 13, 2015·BioMed Research International·Joseph W GoldenRebecca L Brocato
Sep 25, 2015·Journal of Virology·Masaharu IwasakiJuan C de la Torre

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Citations

Jul 17, 2020·Journal of Virology·Chengjin YeLuis Martínez-Sobrido
Jun 9, 2018·Virology Journal·Amélie D ZazaChristophe N Peyrefitte
Jul 30, 2020·Current Opinion in Virology·Chengjin YeLuis Martinez-Sobrido
Mar 2, 2021·PLoS Pathogens·Takaaki KomaSlobodan Paessler
Feb 22, 2021·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Maria G FrankUNKNOWN members of the Medical Countermeasures Working Group of the National Emerging Special Pathogens Training and Education Cente
May 8, 2021·The Journal of General Virology·Joseph W GoldenJay W Hooper

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Datasets Mentioned

BETA
NC005079
KM198592.1
KM198593.1

Methods Mentioned

BETA
ELISA
Illumina sequencing
chips
ELISAs

Software Mentioned

Graphpad Prism
Prinseq
lite
BWA mem
Cutadapt
DNAstar Genequest

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