Plasma Viral miRNAs Indicate a High Prevalence of Occult Viral Infections.

Abstract

Prevalence of Kaposi sarcoma-associated herpesvirus (KSHV/HHV-8) varies greatly in different populations. We hypothesized that the actual prevalence of KSHV/HHV8 infection in humans is underestimated by the currently available serological tests. We analyzed four independent patient cohorts with post-surgical or post-chemotherapy sepsis, chronic lymphocytic leukemia and post-surgical patients with abdominal surgical interventions. Levels of specific KSHV-encoded miRNAs were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and KSHV/HHV-8 IgG were measured by immunoassay. We also measured specific miRNAs from Epstein Barr Virus (EBV), a virus closely related to KSHV/HHV-8, and determined the EBV serological status by ELISA for Epstein-Barr nuclear antigen 1 (EBNA-1) IgG. Finally, we identified the viral miRNAs by in situ hybridization (ISH) in bone marrow cells. In training/validation settings using independent multi-institutional cohorts of 300 plasma samples, we identified in 78.50% of the samples detectable expression of at least one of the three tested KSHV-miRNAs by RT-qPCR, while only 27.57% of samples were found to be seropositive for KSHV/HHV-8 IgG (P<0.001). The prevalence of KSHV infection based on miRNAs qPCR is significantly higher than the prevalence determined by seropositivity, and this is more obvious for immuno-depressed patients. Plasma viral miRNAs quantification proved that EBV infection is ubiquitous. Measurement of viral miRNAs by qPCR has the potential to become the "gold" standard method to detect certain viral infections in clinical practice.

• Authors: Enrique Fuentes-Mattei, Dana Elena Giza, Masayoshi Shimizu, Cristina Ivan, John T Manning, Stefan Tudor, Maria Ciccone, Osman Aykan Kargin, Xinna Zhang, Pilar Mur, Nayra Soares do Amaral, Meng Chen, Jeffrey J Tarrand, Florea Lupu, Alessandra Ferrajoli, Michael J Keating, Catalin Vasilescu, Sai-Ching Jim Yeung, George A Calin
• Journal: EBioMedicine (EBioMedicine) Vol. 20 Pg. 182-192 (Jun 2017) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 28465156 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Viral
• Immunoglobulin G
• MicroRNAs
• RNA, Viral

Topics

• Antibodies, Viral (blood, immunology)
• Cohort Studies
• Enzyme-Linked Immunosorbent Assay
• Herpesvirus 8, Human (genetics, immunology)
• Humans
• Immunoglobulin G (blood, immunology)
• In Situ Hybridization
• Leukocyte Count
• Lymphocyte Count
• MicroRNAs
• Prevalence
• RNA, Viral
• Real-Time Polymerase Chain Reaction
• Reproducibility of Results
• Viral Load
• Virus Diseases (blood, diagnosis, epidemiology, virology)