A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques

David Safronetz, James E. Strong, Friederike Feldmann, Elaine Haddock, Nafomon Sogoba, Douglas Brining, Thomas Geisbert, Dana P. Scott, Heinz Feldmann

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The virulence of Soromba-R, a Lassa virus strain recently isolated from southern Mali, was assessed in 2 animal models of Lassa fever: inbred strain 13 guinea pigs and cynomolgus macaques. In both models, the Malian isolate demonstrated tissue tropism and viral titers similar to those of historical Lassa virus isolates from Sierra Leone (Josiah) and Liberia (Z-132); however, the Soromba-R isolate was found to be less pathogenic, as determined by decreased mortality and prolonged time to euthanasia in macaques. Interestingly, in addition to the classic indicators of Lassa fever, Soromba-R infection presented with moderate to severe pulmonary manifestations in the macaque model. Analysis of host responses demonstrated increased immune activation in Soromba-R-infected macaques, particularly in neutrophil-activating or -potentiating proinflammatory cytokines or growth factors, including tumor necrosis factor α, macrophage inflammatory protein 1α, interleukin 1β, and granulocyte colony-stimulating factor, as well as interleukin 5, which may be responsible for the decreased lethality and uncharacteristic clinical presentation. These results suggest that the strain of Lassa virus circulating in Mali might be less pathogenic than strains circulating in the historical region of endemicity and may result in an atypical presentation for Lassa fever, which could complicate clinical diagnosis.

Original languageEnglish (US)
Pages (from-to)1316-1327
Number of pages12
JournalJournal of Infectious Diseases
Volume207
Issue number8
DOIs
StatePublished - Apr 15 2013

Fingerprint

Lassa virus
Mali
Lassa Fever
Macaca
Virulence
Viral Tropism
Liberia
Sierra Leone
Macrophage Inflammatory Proteins
Euthanasia
Interleukin-5
Granulocyte Colony-Stimulating Factor
Interleukin-1
Intercellular Signaling Peptides and Proteins
Guinea Pigs
Neutrophils
Animal Models
Tumor Necrosis Factor-alpha
Cytokines
Lung

Keywords

  • disease modeling
  • guinea pigs
  • Lassa fever
  • non-human primates
  • pathogenesis
  • West Africa

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques. / Safronetz, David; Strong, James E.; Feldmann, Friederike; Haddock, Elaine; Sogoba, Nafomon; Brining, Douglas; Geisbert, Thomas; Scott, Dana P.; Feldmann, Heinz.

In: Journal of Infectious Diseases, Vol. 207, No. 8, 15.04.2013, p. 1316-1327.

Research output: Contribution to journalArticle

Safronetz, David ; Strong, James E. ; Feldmann, Friederike ; Haddock, Elaine ; Sogoba, Nafomon ; Brining, Douglas ; Geisbert, Thomas ; Scott, Dana P. ; Feldmann, Heinz. / A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques. In: Journal of Infectious Diseases. 2013 ; Vol. 207, No. 8. pp. 1316-1327.
@article{cc936ddbe1004e89bf9844bfdf583b86,
title = "A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques",
abstract = "The virulence of Soromba-R, a Lassa virus strain recently isolated from southern Mali, was assessed in 2 animal models of Lassa fever: inbred strain 13 guinea pigs and cynomolgus macaques. In both models, the Malian isolate demonstrated tissue tropism and viral titers similar to those of historical Lassa virus isolates from Sierra Leone (Josiah) and Liberia (Z-132); however, the Soromba-R isolate was found to be less pathogenic, as determined by decreased mortality and prolonged time to euthanasia in macaques. Interestingly, in addition to the classic indicators of Lassa fever, Soromba-R infection presented with moderate to severe pulmonary manifestations in the macaque model. Analysis of host responses demonstrated increased immune activation in Soromba-R-infected macaques, particularly in neutrophil-activating or -potentiating proinflammatory cytokines or growth factors, including tumor necrosis factor α, macrophage inflammatory protein 1α, interleukin 1β, and granulocyte colony-stimulating factor, as well as interleukin 5, which may be responsible for the decreased lethality and uncharacteristic clinical presentation. These results suggest that the strain of Lassa virus circulating in Mali might be less pathogenic than strains circulating in the historical region of endemicity and may result in an atypical presentation for Lassa fever, which could complicate clinical diagnosis.",
keywords = "disease modeling, guinea pigs, Lassa fever, non-human primates, pathogenesis, West Africa",
author = "David Safronetz and Strong, {James E.} and Friederike Feldmann and Elaine Haddock and Nafomon Sogoba and Douglas Brining and Thomas Geisbert and Scott, {Dana P.} and Heinz Feldmann",
year = "2013",
month = "4",
day = "15",
doi = "10.1093/infdis/jit004",
language = "English (US)",
volume = "207",
pages = "1316--1327",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques

AU - Safronetz, David

AU - Strong, James E.

AU - Feldmann, Friederike

AU - Haddock, Elaine

AU - Sogoba, Nafomon

AU - Brining, Douglas

AU - Geisbert, Thomas

AU - Scott, Dana P.

AU - Feldmann, Heinz

PY - 2013/4/15

Y1 - 2013/4/15

N2 - The virulence of Soromba-R, a Lassa virus strain recently isolated from southern Mali, was assessed in 2 animal models of Lassa fever: inbred strain 13 guinea pigs and cynomolgus macaques. In both models, the Malian isolate demonstrated tissue tropism and viral titers similar to those of historical Lassa virus isolates from Sierra Leone (Josiah) and Liberia (Z-132); however, the Soromba-R isolate was found to be less pathogenic, as determined by decreased mortality and prolonged time to euthanasia in macaques. Interestingly, in addition to the classic indicators of Lassa fever, Soromba-R infection presented with moderate to severe pulmonary manifestations in the macaque model. Analysis of host responses demonstrated increased immune activation in Soromba-R-infected macaques, particularly in neutrophil-activating or -potentiating proinflammatory cytokines or growth factors, including tumor necrosis factor α, macrophage inflammatory protein 1α, interleukin 1β, and granulocyte colony-stimulating factor, as well as interleukin 5, which may be responsible for the decreased lethality and uncharacteristic clinical presentation. These results suggest that the strain of Lassa virus circulating in Mali might be less pathogenic than strains circulating in the historical region of endemicity and may result in an atypical presentation for Lassa fever, which could complicate clinical diagnosis.

AB - The virulence of Soromba-R, a Lassa virus strain recently isolated from southern Mali, was assessed in 2 animal models of Lassa fever: inbred strain 13 guinea pigs and cynomolgus macaques. In both models, the Malian isolate demonstrated tissue tropism and viral titers similar to those of historical Lassa virus isolates from Sierra Leone (Josiah) and Liberia (Z-132); however, the Soromba-R isolate was found to be less pathogenic, as determined by decreased mortality and prolonged time to euthanasia in macaques. Interestingly, in addition to the classic indicators of Lassa fever, Soromba-R infection presented with moderate to severe pulmonary manifestations in the macaque model. Analysis of host responses demonstrated increased immune activation in Soromba-R-infected macaques, particularly in neutrophil-activating or -potentiating proinflammatory cytokines or growth factors, including tumor necrosis factor α, macrophage inflammatory protein 1α, interleukin 1β, and granulocyte colony-stimulating factor, as well as interleukin 5, which may be responsible for the decreased lethality and uncharacteristic clinical presentation. These results suggest that the strain of Lassa virus circulating in Mali might be less pathogenic than strains circulating in the historical region of endemicity and may result in an atypical presentation for Lassa fever, which could complicate clinical diagnosis.

KW - disease modeling

KW - guinea pigs

KW - Lassa fever

KW - non-human primates

KW - pathogenesis

KW - West Africa

UR - http://www.scopus.com/inward/record.url?scp=84875582037&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875582037&partnerID=8YFLogxK

U2 - 10.1093/infdis/jit004

DO - 10.1093/infdis/jit004

M3 - Article

VL - 207

SP - 1316

EP - 1327

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 8

ER -