Related Experiment Video
Updated: Apr 19, 2026
Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus KSHV
Published on: September 14, 2010
Cellular and Kaposi's sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma
11] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Surgery, Fundeni Clinical Hospital, Bucharest, Romania.
Abstract:
Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation.
Insights
Cellular and viral microRNAs (miRNAs) show promise as sepsis biomarkers. Specific Kaposi sarcoma herpes virus (KSHV) miRNAs, miR-K-10b and miR-K-12-12*, are elevated in sepsis and may drive inflammation via Toll-like receptor 8 (TLR8).
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Sepsis diagnosis and triage are critical, as survival rates decrease significantly with delayed antibiotic treatment.
- Identifying reliable biomarkers for sepsis is essential for timely intervention and improved patient outcomes.
- MicroRNAs (miRNAs) are emerging as potential diagnostic and prognostic indicators in various diseases, including sepsis.
Purpose of the Study:
- To investigate the potential of cellular and viral microRNAs (miRNAs) as biomarkers for sepsis diagnosis.
- To explore the functional role of Kaposi sarcoma herpes virus (KSHV) miRNAs in sepsis-associated inflammation.
- To determine the impact of KSHV miRNAs on cytokine secretion and their mechanism of action.
Main Methods:
- Genome-wide miRNA expression profiling in leukocytes from septic and nonseptic individuals.
- Quantitative RT-PCR analysis of plasma miRNAs in multiple patient cohorts (septic, nonseptic surgical, healthy).
- Enzyme-linked immunosorbent assay (ELISA), miRNA transfection, and chromatin immunoprecipitation to study KSHV miRNA function.
Main Results:
- Plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b, miR-K-12-12*) differed significantly between septic and nonseptic patients.
- Elevated levels of KSHV miRNAs were observed in septic patients compared to controls; Afro-American patients showed higher miR-K-12-12* levels.
- KSHV miRNAs acted as direct agonists of Toll-like receptor 8 (TLR8), leading to increased secretion of IL-6 and IL-10, suggesting a positive feedback loop in sepsis.
Conclusions:
- Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients, indicating their potential as diagnostic biomarkers.
- Increased miR-K-10b and miR-K-12-12* are functionally implicated in sepsis pathogenesis by activating TLR8 and promoting cytokine dysregulation.
- These findings suggest that KSHV miRNAs could be valuable targets for novel diagnostic and therapeutic strategies in sepsis management.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs
01:27Cytomegalovirus Disease