Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection

BMC Genomics

John H Connor³  Arthur J Goff⁴  Anna N Honko²  Lisa E Hensley²  Judy Y Yen³  Ignacio S Caballero¹ 

[1] Bioinformatics Graduate Program, Boston University, 24 Cummington St, Boston, MA 02215, USA;Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702, USA;Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA;Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA

关键词: Early stage diagnostics;    Gene expression profile;    Biomarker;    Interferon-stimulated genes;    Marburg virus;    Lassa virus;    Transcriptional response;    Transcriptomics;   

Others  :  1127730
DOI  :  10.1186/1471-2164-15-960

 received in 2014-06-20, accepted in 2014-10-22,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Caballero et al.; licensee BioMed Central Ltd.

【 图 表 】

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