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

Abstract

The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established. Based on 44 publicly available datasets and two clinical studies of our own design, we discovered and validated a four-gene expression signature in whole blood, indicative of a general host systemic response to many types of viral infection. The signature’s genes are: Interferon Stimulated Gene 15 (ISG15), Interleukin 16 (IL16), 2′,5′-Oligoadenylate Synthetase Like (OASL), and Adhesion G Protein Coupled Receptor E5 (ADGRE5). In each of 13 validation datasets encompassing human, macaque, chimpanzee, pig, mouse, rat and all seven Baltimore virus classification groups, the signature provides statistically significant (p < 0.05) discrimination between viral and non-viral conditions. The signature may have clinical utility for differentiating host systemic inflammation (SI) due to viral versus bacterial or non-infectious causes.

Viral Sepsis in Children

“…In a recent study by Herberg et al, a 2-transcript RNA signature [ FAM89A and IFI44L ) showed promising results in its ability to distinguish between bacterial and viral infections, demonstrating that the expression of IFI44L was increased in patients with viral infection, whereas expression of FAM89A was increased in patients with bacterial infection ( 118 ). Another recent study identified a four-gene expression signature in whole blood to distinguish viral infections from other etiologies ( 129 ). Human myxovirus resistance protein 1 (MxA) is an important intermediate product in the IFN-mediated antiviral response against a variety of viruses.…”

IFN-Stimulated Gene 15 Is an Alarmin that Boosts the CTL Response via an Innate, NK Cell–Dependent Route

“…This group of proteins includes ISG15 that has a diubiquitin-like structure (2). Isg15 is one of the genes most strongly upregulated in response to viral infection in a diversity of species, including humans (3,4). ISG15 is also induced by bacterial infections (5,6).…”

Sepsis Diagnostics in the Era of “Omics” Technologies

“…Interestingly study failed to identify an immune response specific to bacterial pneumonia (Parnell et al, 2012). A study by Sampson et al (2017) which revealed different gene expression depending on virus or bacterial etiology, produced similar results. Should these abilities of a specific group of genes be confirmed, there is a real possibility of their implementation in clinical practice, which would affect antibiotic consumption, resistance development, etc.…”