Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection.
BACKGROUND
Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever. Their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. Current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. Using the transcriptional response of the host during infection can lead to earlier diagnoses compared to those of traditional methods.


RESULTS
In this study, we use RNA sequencing to obtain a high-resolution view of the in vivo transcriptional dynamics of peripheral blood mononuclear cells (PBMCs) throughout both types of infection. We report a subset of host mRNAs, including heat-shock proteins like HSPA1B, immunoglobulins like IGJ, and cell adhesion molecules like SIGLEC1, whose differences in expression are strong enough to distinguish Lassa infection from Marburg infection in non-human primates. We have validated these infection-specific expression differences by using microarrays on a larger set of samples, and by quantifying the expression of individual genes using RT-PCR.


CONCLUSIONS
These results suggest that host transcriptional signatures are correlated with specific viral infections, and that they can be used to identify highly pathogenic viruses during the early stages of disease, before standard detection methods become effective.
Bioinformatics Graduate Program, Boston University, 24 Cummington St, Boston, MA 02215, USA. nacho@bu.edu.
Ignacio S
IS
Caballero
Judy Y
JY
Yen
Lisa E
LE
Hensley
Anna N
AN
Honko
Arthur J
AJ
Goff
John H
JH
Connor
D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006482:Hemorrhagic Fevers, Viral / Q000662:veterinary*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D007370:Interferon Type I / Q000494:pharmacology; D007836:Lassa virus; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008252:Macaca fascicularis; D008297:Male; D029024:Marburgvirus; D008992:Monkey Diseases / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
D007370:Interferon Type I