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Tytuł pozycji:

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

Tytuł:
An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection.
Autorzy:
Golden JW; Department of Molecular Virology, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, 21702, United States. .
Beitzel B; Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, 21702, United States.
Ladner JT; Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, 21702, United States.
Mucker EM; Department of Molecular Virology, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, 21702, United States.
Kwilas SA; Department of Molecular Virology, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, 21702, United States.
Palacios G; Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, 21702, United States.
Hooper JW; Department of Molecular Virology, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, 21702, United States.
Źródło:
Scientific reports [Sci Rep] 2017 Jul 05; Vol. 7 (1), pp. 4679. Date of Electronic Publication: 2017 Jul 05.
Typ publikacji:
Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
Język:
English
Imprint Name(s):
Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:
DNA, Intergenic*
Arenaviridae Infections/*prevention & control
Arenaviruses, New World/*pathogenicity
Sequence Analysis, RNA/*methods
Vaccines, Attenuated/*genetics
Animals ; Arenaviruses, New World/genetics ; Arenaviruses, New World/isolation & purification ; Cell Line ; Chlorocebus aethiops ; Disease Models, Animal ; Female ; Guinea Pigs ; Human Umbilical Vein Endothelial Cells ; Humans ; Point Mutation ; RNA, Viral/genetics ; Sequence Deletion ; Vaccines, Attenuated/isolation & purification ; Vero Cells ; Virulence Factors/genetics
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Substance Nomenclature:
0 (DNA, Intergenic)
0 (RNA, Viral)
0 (Vaccines, Attenuated)
0 (Virulence Factors)
Entry Date(s):
Date Created: 20170707 Date Completed: 20190128 Latest Revision: 20231112
Update Code:
20240104
PubMed Central ID:
PMC5498534
DOI:
10.1038/s41598-017-04889-x
PMID:
28680057
Czasopismo naukowe
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 Car 91 that was attenuated in guinea pigs. Infection of guinea pigs with an earlier passage of Carvallo, termed Car 68 , resulted in a lethal disease with a 63% mortality rate. Sequencing analysis revealed that compared to Car 68 , Car 91 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 Car 91 could protect guinea pigs against Guanarito virus (GTOV), a distantly related NW arenavirus. While naïve animals succumbed to GTOV infection, 88% of the Car 91 -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 of live-attenuated arenaviruses as broadly protective pan-arenavirus vaccines.

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