Early blood profiles of virus infection in a monkey model for Lassa fever.
Acute arenavirus disease in primates, like Lassa hemorrhagic fever in humans, begins with flu-like symptoms and leads to death approximately 2 weeks after infection. Our goal was to identify molecular changes in blood that are related to disease progression. Rhesus macaques (Macaca mulatta) infected intravenously with a lethal dose of lymphocytic choriomeningitis virus (LCMV) provide a model for Lassa virus infection of humans. Blood samples taken before and during the course of infection were used to monitor gene expression changes that paralleled disease onset. Changes in blood showed major disruptions in eicosanoid, immune response, and hormone response pathways. Approximately 12% of host genes alter their expression after LCMV infection, and a subset of these genes can discriminate between virulent and non-virulent LCMV infection. Major transcription changes have been given preliminary confirmation by quantitative PCR and protein studies and will be valuable candidates for future validation as biomarkers for arenavirus disease.
Djavani
Mahmoud M
MM
Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard St., Baltimore, MD 21201, USA.
Crasta
Oswald R
OR
Zapata
Juan Carlos
JC
Fei
Zhangjun
Z
Folkerts
Otto
O
Sobral
Bruno
B
Swindells
Mark
M
Bryant
Joseph
J
Davis
Harry
H
Pauza
C David
CD
Lukashevich
Igor S
IS
Hammamieh
Rasha
R
Jett
Marti
M
Salvato
Maria S
MS
D000818:Animals; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007835:Lassa Fever / Q000097:blood*; D007836:Lassa virus / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000378:metabolism; D008253:Macaca mulatta / Q000097:blood / Q000821:virology; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000097:blood / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D014766:Viremia
D018925:Chemokines; D016207:Cytokines