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

Caballero IS, Yen JY, Hensley LE, Honko AN, Goff AJ, Connor JH - BMC Genomics (2014)

Bottom Line: Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever.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.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.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Graduate Program, Boston University, 24 Cummington St, Boston, MA 02215, USA. nacho@bu.edu.

ABSTRACT

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.

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Related in: MedlinePlus

Genes showing similar patterns of expression during Lassa virus and Marburg virus infection. Each point represents the level of expression (measured in log10 normalized read counts) of a gene that behaves similarly in both types of infection (increasingly darker shades of blue for Lassa, and red for Marburg). Panel (A) represents the expression of gene IFI44L showing time in the x-axis. Panel (B) condenses the information in (A) and shows additional genes along the x-axis.
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Fig2: Genes showing similar patterns of expression during Lassa virus and Marburg virus infection. Each point represents the level of expression (measured in log10 normalized read counts) of a gene that behaves similarly in both types of infection (increasingly darker shades of blue for Lassa, and red for Marburg). Panel (A) represents the expression of gene IFI44L showing time in the x-axis. Panel (B) condenses the information in (A) and shows additional genes along the x-axis.

Mentions: To identify what transcriptional changes are shared by different hemorrhagic fever virus infections, we identified genes whose levels of expression 1) closely matched in both types of viral challenge, 2) strongly increased or decreased 3 days post-infection (dpi), and 3) increased or sustained this level of expression throughout the remaining time points (5–10 dpi). We labeled this group of genes the common response (Figure 2B). Some of its representative members include transcription factors IRF7 and STAT1, which serve as master regulators of host immunity; pattern recognition receptors DDX58 (RIG-I), IFIH1 (MDA-5) and DHX58 (LGP2), which activate different signaling cascades in the innate immune system; type I interferon-stimulated genes ISG15, ISG20, OAS1, OAS2, OASL, MX1, IFIT1, IFIT2, IFIT3, HERC5, HERC6, IFI6, IFI35, IFI44 and IFI44L, which play a variety of antiviral roles [22]; and the cytokine CXCL10, which attracts activated T cells [23] (Additional file 1).Figure 2


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

Caballero IS, Yen JY, Hensley LE, Honko AN, Goff AJ, Connor JH - BMC Genomics (2014)

Genes showing similar patterns of expression during Lassa virus and Marburg virus infection. Each point represents the level of expression (measured in log10 normalized read counts) of a gene that behaves similarly in both types of infection (increasingly darker shades of blue for Lassa, and red for Marburg). Panel (A) represents the expression of gene IFI44L showing time in the x-axis. Panel (B) condenses the information in (A) and shows additional genes along the x-axis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4232721&req=5

Fig2: Genes showing similar patterns of expression during Lassa virus and Marburg virus infection. Each point represents the level of expression (measured in log10 normalized read counts) of a gene that behaves similarly in both types of infection (increasingly darker shades of blue for Lassa, and red for Marburg). Panel (A) represents the expression of gene IFI44L showing time in the x-axis. Panel (B) condenses the information in (A) and shows additional genes along the x-axis.
Mentions: To identify what transcriptional changes are shared by different hemorrhagic fever virus infections, we identified genes whose levels of expression 1) closely matched in both types of viral challenge, 2) strongly increased or decreased 3 days post-infection (dpi), and 3) increased or sustained this level of expression throughout the remaining time points (5–10 dpi). We labeled this group of genes the common response (Figure 2B). Some of its representative members include transcription factors IRF7 and STAT1, which serve as master regulators of host immunity; pattern recognition receptors DDX58 (RIG-I), IFIH1 (MDA-5) and DHX58 (LGP2), which activate different signaling cascades in the innate immune system; type I interferon-stimulated genes ISG15, ISG20, OAS1, OAS2, OASL, MX1, IFIT1, IFIT2, IFIT3, HERC5, HERC6, IFI6, IFI35, IFI44 and IFI44L, which play a variety of antiviral roles [22]; and the cytokine CXCL10, which attracts activated T cells [23] (Additional file 1).Figure 2

Bottom Line: Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever.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.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.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Graduate Program, Boston University, 24 Cummington St, Boston, MA 02215, USA. nacho@bu.edu.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus