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Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

Abstract Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality.
PMID
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Authors

Mayor MeshTerms

Host-Pathogen Interactions

Virus Replication

Keywords

2C protein

Adult mice

Capsid

FMDV

Lethality

Pathogenesis

Journal Title virology
Publication Year Start




PMID- 28647507
OWN - NLM
STAT- MEDLINE
DA  - 20170625
DCOM- 20170721
LR  - 20170721
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Linking)
VI  - 509
DP  - 2017 Sep
TI  - Differential replication of Foot-and-mouth disease viruses in mice determine
      lethality.
PG  - 195-204
LID - S0042-6822(17)30190-3 [pii]
LID - 10.1016/j.virol.2017.06.012 [doi]
AB  - Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV)
      biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting
      differential pathogenicity in adult mice were identified and characterized: a
      non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus
      (A01L) caused death within 24-48h independently of the dose used. Both viruses
      caused a systemic infection with pathological changes in the exocrine pancreas.
      Virus A01L reached higher viral loads in plasma and organs of inoculated mice as 
      well as increased replication in an ovine kidney cell line. Complete consensus
      sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that
      might be linked to replication differences, as suggested by in silico prediction 
      studies. Our results highlight the biological significance of discrete genomic
      variations and reinforce the usefulness of this animal model to study viral
      determinants of lethality.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Cacciabue, Marco
AU  - Cacciabue M
AD  - Instituto de Biotecnologia, Instituto Nacional de Tecnologia Agropecuaria (INTA),
      De los Reseros y N. Repetto s/n, (1686) Hurlingham, Argentina; Consejo Nacional
      de Investigaciones Cientificas y Tecnicas (CONICET), Argentina. Electronic
      address: [email protected]
FAU - Garcia-Nunez, Maria Soledad
AU  - Garcia-Nunez MS
AD  - Instituto de Biotecnologia, Instituto Nacional de Tecnologia Agropecuaria (INTA),
      De los Reseros y N. Repetto s/n, (1686) Hurlingham, Argentina. Electronic
      address: [email protected]
FAU - Delgado, Fernando
AU  - Delgado F
AD  - Instituto de Patobiologia, INTA, De los Reseros y N. Repetto s/n, (1686)
      Hurlingham, Argentina. Electronic address: [email protected]
FAU - Curra, Anabella
AU  - Curra A
AD  - Instituto de Biotecnologia, Instituto Nacional de Tecnologia Agropecuaria (INTA),
      De los Reseros y N. Repetto s/n, (1686) Hurlingham, Argentina; Consejo Nacional
      de Investigaciones Cientificas y Tecnicas (CONICET), Argentina. Electronic
      address: [email protected]
FAU - Marrero, Ruben
AU  - Marrero R
AD  - Instituto de Biotecnologia, Instituto Nacional de Tecnologia Agropecuaria (INTA),
      De los Reseros y N. Repetto s/n, (1686) Hurlingham, Argentina. Electronic
      address: [email protected]
FAU - Molinari, Paula
AU  - Molinari P
AD  - Instituto de Biotecnologia, Instituto Nacional de Tecnologia Agropecuaria (INTA),
      De los Reseros y N. Repetto s/n, (1686) Hurlingham, Argentina; Consejo Nacional
      de Investigaciones Cientificas y Tecnicas (CONICET), Argentina. Electronic
      address: [email protected]
FAU - Rieder, Elizabeth
AU  - Rieder E
AD  - Foreign Animal Disease Research Unit, United States Department of Agriculture,
      Agricultural Research Service, Plum Island Animal Disease Center, PO Box 848,
      Greenport, NY11944-0848, USA. Electronic address: [email protected]
FAU - Carrillo, Elisa
AU  - Carrillo E
AD  - Centro de Investigacion en Ciencias Veterinarias y Agronomicas (CICVyA), INTA, De
      los Reseros y N. Repetto s/n, (1686) Hurlingham, Argentina; Consejo Nacional de
      Investigaciones Cientificas y Tecnicas (CONICET), Argentina. Electronic address: 
      [email protected]
FAU - Gismondi, Maria Ines
AU  - Gismondi MI
AD  - Instituto de Biotecnologia, Instituto Nacional de Tecnologia Agropecuaria (INTA),
      De los Reseros y N. Repetto s/n, (1686) Hurlingham, Argentina; Consejo Nacional
      de Investigaciones Cientificas y Tecnicas (CONICET), Argentina. Electronic
      address: [email protected]
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20170623
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
SB  - IM
MH  - Animal Structures/virology
MH  - Animals
MH  - Cell Line
MH  - Disease Models, Animal
MH  - Foot-and-Mouth Disease/*pathology/*virology
MH  - Foot-and-Mouth Disease Virus/*pathogenicity/physiology
MH  - *Host-Pathogen Interactions
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutation, Missense
MH  - Pancreas/pathology
MH  - Plasma/virology
MH  - Sequence Analysis, DNA
MH  - Survival Analysis
MH  - Viral Load
MH  - *Virus Replication
OTO - NOTNLM
OT  - 2C protein
OT  - Adult mice
OT  - Capsid
OT  - FMDV
OT  - Lethality
OT  - Pathogenesis
EDAT- 2017/06/26 06:00
MHDA- 2017/07/22 06:00
CRDT- 2017/06/26 06:00
PHST- 2017/02/01 [received]
PHST- 2017/06/01 [revised]
PHST- 2017/06/12 [accepted]
AID - S0042-6822(17)30190-3 [pii]
AID - 10.1016/j.virol.2017.06.012 [doi]
PST - ppublish
SO  - Virology. 2017 Sep;509:195-204. doi: 10.1016/j.virol.2017.06.012. Epub 2017 Jun
      23.