2015
DOI: 10.1128/jvi.02246-14
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Delayed Inflammatory and Cell Death Responses Are Associated with Reduced Pathogenicity in Lujo Virus-Infected Cynomolgus Macaques

Abstract: To identify host factors associated with arenavirus virulence, we used a cynomolgus macaque model to evaluate the pathogenesis of Lujo virus (LUJV), a recently emerged arenavirus that caused an outbreak of severe viral hemorrhagic fever in southern Africa. In contrast to human cases, LUJV caused mild, nonlethal illness in macaques. We then compared this to contrasting clinical outcomes during arenavirus infection, specifically to samples obtained from macaques infected with three highly pathogenic lines of Las… Show more

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Cited by 11 publications
(12 citation statements)
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References 40 publications
(47 reference statements)
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“…Animals are leukopenic, have a slight decrease in platelet counts, and are consistent with liver involvement, raised liver enzymes (ALT and AST). Cynomolgus macaques exposed to LASV (Josiah or Z-132) have a similar clinical presentation, with the exception that facial edema was a prominent early sign and some neurological manifestations were observed [ 101 , 115 , 120 , 157 ]. However, not all cases of NHP infection by human pathogenic OW arenaviruses represent a transcript of the human disease.…”
Section: Arenavirus Animal Modelsmentioning
confidence: 99%
See 1 more Smart Citation
“…Animals are leukopenic, have a slight decrease in platelet counts, and are consistent with liver involvement, raised liver enzymes (ALT and AST). Cynomolgus macaques exposed to LASV (Josiah or Z-132) have a similar clinical presentation, with the exception that facial edema was a prominent early sign and some neurological manifestations were observed [ 101 , 115 , 120 , 157 ]. However, not all cases of NHP infection by human pathogenic OW arenaviruses represent a transcript of the human disease.…”
Section: Arenavirus Animal Modelsmentioning
confidence: 99%
“…However, not all cases of NHP infection by human pathogenic OW arenaviruses represent a transcript of the human disease. LUJV, lethal in 4 of 5 human cases, produced only mild illness in cynomolgus macaques [ 120 ]. Similarly, LASV isolated from a fatal case (strain AV) had an alternative disease course and failed to produce uniformly fatal disease in NHPs [ 160 ].…”
Section: Arenavirus Animal Modelsmentioning
confidence: 99%
“…NK cell responses are important for survival in human Ebola virus disease cases ( 28 , 29 ). Differences in the timing of NK cell responses are a key difference in non-lethal, mild disease and lethal, severe (Lassa virus) infections in macaques ( 30 ), suggesting the species-specific NK cell responses observed here warrant further exploration. For comparison, and as described in the accompanying paper by Buechler et al ., olive baboons and rhesus monkeys infected with SWBV-1 also developed increases in NK and CD8 + T-cell numbers, with CD8 + T-cell numbers remaining elevated through the observation period.…”
Section: Discussionmentioning
confidence: 87%
“…NK cell responses are important for survival in human Ebola virus disease cases [29,30]. Differences in the timing of NK cell responses are also a key difference in non-lethal, mild disease and lethal, severe Lassa virus infections in macaques [31], suggesting the species-specific NK cell responses observed here warrant further exploration. For comparison, and as described in the recent paper by Buechler et al [11], olive baboons and rhesus monkeys infected with the SHFV-related Southwest baboon virus 1 (SWBV-1) also developed increases in NK and CD8 + T-cell numbers, with CD8 + T-cell frequency remained elevated throughout the observation period.…”
Section: Discussionmentioning
confidence: 96%