Delayed Inflammatory and Cell Death Responses Are Associated with Reduced Pathogenicity in Lujo Virus-Infected Cynomolgus Macaques

• DOI: 10.1128/jvi.02246-14
• Publication Date: 2014-12-18T15:27:14Z
• Authors: Angela L. Rasmussen; Nicolas Tchitchek; David Safronetz; Victoria S. Carter; Christopher M. Wi...; Elaine Haddock; Marcus J. Korth; Heinz Feldmann; Michael G. Katze
• Keywords: Arenavirus

To identify host factors associated with arenavirus virulence, we used a cynomolgus macaque model to evaluate the pathogenesis of Lujo virus (LUJV), recently emerged that caused an outbreak severe viral hemorrhagic fever in southern Africa. In contrast human cases, LUJV mild, nonlethal illness macaques. We then compared this contrasting clinical outcomes during infection, specifically samples obtained from macaques infected three highly pathogenic lines Lassa (LASV), causative agent (LF). assessed gene expression peripheral blood mononuclear cells (PBMC) and determined genes significantly changed relative uninfected animals over course infection. detected 72-h delay induction responses infection LASV. This included inflammatory antiviral was particularly apparent among groups promoting cell death. also observed early differential subset specific accounts for delayed response. Cell type enrichment analysis suggested response LUJV-specific profile are due different proportion natural killer responding than LASV-infected animals. Together, these data indicate proinflammatory proapoptotic could ameliorate disease severity. conclusion provides insight into cellular molecular mechanisms arenaviral suggests potential strategies therapeutic development. Old World arenaviruses significant pathogens often high mortality. However, underlying severity virulence largely unknown, regarding contribute pathogenicity. study describes comparison between virus-infected developed only mild illness, while consistent fever. is linked such as those causing inflammation death, distinct types may mediate delay. first associate timing directionality pathogenicity outcome evokes new approaches developing effective therapeutics treating deadly emerging pathogens.