A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies

Area of Science:

• Immunology
• Genomics
• Infectious Diseases

Background:

• The innate immune system recognizes conserved pathogen-associated molecular patterns (PAMPs).
• Previous research identified virus-specific host transcriptional signatures, but their generalizability was unproven.

Purpose of the Study:

• To discover and validate a general blood-based transcriptional signature indicative of a systemic host response to viral infection.
• To assess the clinical utility of this signature in differentiating viral infections from other causes of inflammation.

Main Methods:

• Analysis of 44 public datasets and two custom clinical studies.
• Discovery and validation of a four-gene expression signature in whole blood.
• Testing the signature's discriminatory power across diverse host species and viral classification groups.

Main Results:

• A four-gene signature (ISG15, IL16, OASL, ADGRE5) was identified and validated.
• The signature demonstrated statistically significant discrimination between viral and non-viral conditions in 13 independent datasets.
• The signature showed effectiveness across various species (human, macaque, chimpanzee, pig, mouse, rat) and all seven Baltimore virus classification groups.

Conclusions:

• A conserved, four-gene blood signature effectively indicates a systemic host response to a wide range of viral infections.
• This signature holds potential clinical utility for distinguishing viral systemic inflammation (SI) from bacterial or non-infectious etiologies.