Novel poly-uridine insertion in the 3'UTR and E2 amino acid substitutions in a low virulent classical swine fever virus

TY - JOUR

T1 - Novel poly-uridine insertion in the 3'UTR and E2 amino acid substitutions in a low virulent classical swine fever virus

AU - Coronado, Liani

AU - Liniger, Matthias

AU - Muñoz-González, Sara

AU - Postel, Alexander

AU - Pérez, Lester Josue

AU - Pérez-Simó, Marta

AU - Perera, Carmen Laura

AU - Frías-Lepoureau, Maria Teresa

AU - Rosell, Rosa

AU - Grundhoff, Adam

AU - Indenbirken, Daniela

AU - Alawi, Malik

AU - Fischer, Nicole

AU - Becher, Paul

AU - Ruggli, Nicolas

AU - Ganges, Llilianne

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2017/3

Y1 - 2017/3

N2 - In this study, we compared the virulence in weaner pigs of the Pinar del Rio isolate and the virulent Margarita strain. The latter caused the Cuban classical swine fever (CSF) outbreak of 1993. Our results showed that the Pinar del Rio virus isolated during an endemic phase is clearly of low virulence. We analysed the complete nucleotide sequence of the Pinar del Rio virus isolated after persistence in newborn piglets, as well as the genome sequence of the inoculum. The consensus genome sequence of the Pinar del Rio virus remained completely unchanged after 28days of persistent infection in swine. More importantly, a unique poly-uridine tract was discovered in the 3'UTR of the Pinar del Rio virus, which was not found in the Margarita virus or any other known CSFV sequences. Based on RNA secondary structure prediction, the poly-uridine tract results in a long single-stranded intervening sequence (SS) between the stem-loops I and II of the 3'UTR, without major changes in the stem- loop structures when compared to the Margarita virus. The possible implications of this novel insertion on persistence and attenuation remain to be investigated. In addition, comparison of the amino acid sequence of the viral proteins E(rns), E1, E2 and p7 of the Margarita and Pinar del Rio viruses showed that all non-conservative amino acid substitutions acquired by the Pinar del Rio isolate clustered in E2, with two of them being located within the B/C domain. Immunisation and cross-neutralisation experiments in pigs and rabbits suggest differences between these two viruses, which may be attributable to the amino acid differences observed in E2. Altogether, these data provide fresh insights into viral molecular features which might be associated with the attenuation and adaptation of CSFV for persistence in the field.

AB - In this study, we compared the virulence in weaner pigs of the Pinar del Rio isolate and the virulent Margarita strain. The latter caused the Cuban classical swine fever (CSF) outbreak of 1993. Our results showed that the Pinar del Rio virus isolated during an endemic phase is clearly of low virulence. We analysed the complete nucleotide sequence of the Pinar del Rio virus isolated after persistence in newborn piglets, as well as the genome sequence of the inoculum. The consensus genome sequence of the Pinar del Rio virus remained completely unchanged after 28days of persistent infection in swine. More importantly, a unique poly-uridine tract was discovered in the 3'UTR of the Pinar del Rio virus, which was not found in the Margarita virus or any other known CSFV sequences. Based on RNA secondary structure prediction, the poly-uridine tract results in a long single-stranded intervening sequence (SS) between the stem-loops I and II of the 3'UTR, without major changes in the stem- loop structures when compared to the Margarita virus. The possible implications of this novel insertion on persistence and attenuation remain to be investigated. In addition, comparison of the amino acid sequence of the viral proteins E(rns), E1, E2 and p7 of the Margarita and Pinar del Rio viruses showed that all non-conservative amino acid substitutions acquired by the Pinar del Rio isolate clustered in E2, with two of them being located within the B/C domain. Immunisation and cross-neutralisation experiments in pigs and rabbits suggest differences between these two viruses, which may be attributable to the amino acid differences observed in E2. Altogether, these data provide fresh insights into viral molecular features which might be associated with the attenuation and adaptation of CSFV for persistence in the field.

KW - Journal Article

U2 - 10.1016/j.vetmic.2017.01.013

DO - 10.1016/j.vetmic.2017.01.013

M3 - SCORING: Journal article

C2 - 28284595

VL - 201

SP - 103

EP - 112

JO - VET MICROBIOL

JF - VET MICROBIOL

SN - 0378-1135

ER -