HANTAVIRUS INDUCED CHANGES IN T-CELL AND SHOWED UP-REGULATION OF PRO-INFLAMMATORY CYTOKINES RELATED WITH DISEASE SEVERITY

PERIOLO NATALIA,; IGLESIAS AYELÉN; ALONSO DANIEL; BELLOMO CARLA; MARTINEZ VALERIA

Palm Beach

Simposio; ASM Clinical Virology Symposium; 2018

American Society for Microbiology

Background: Hantaviruses are emerging human pathogens. These zoonotic viruses are responsible of two different clinical presentations, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Hantaviruses predominantly infect microvascular endothelial cells causing capillary leakage. The hallmark of hantavirus diseases is the vascular permeability, which leads to pulmonary edema in HPS patients. Andes virus is the causative agent of HPS in Argentina and neighboring countries it is associated to high case fatality rates.Methods: To evaluate the role of the immune response on pathogenesis we analyzed cytokine profiles and the activation state of T cells in patients, we study HPS patients corresponded with died patients (D) and survivors (S). Control samples were taken from healthy adult volunteers (HV). Blood samples were collected to analyze activation markets on T cell subpopulations by flow cytometry. Statistical analysis was performed using Student?s t- using GraphPad software version 5.0.Serum cytokine levels were analyzed using multiplex magnetic bead-based technology by a Luminex 200 analyzer. Results: Analysis of T cells subset showed increase in CD8 expression and decrease of CD4 in patients, resulting in an alteration of the CD4/CD8 ratio compared to HV. The phenotypic analysis of TCD8 cell subpopulations showed an activation state. Interestingly, we showed an increase of Granzyme A and B in patient´s sera in D to compared with HV. In addition, we observed high expression of classic monocytes (CD14+CD16+) in patients compared with HV. We found significant higher levels of for IL-4, IL-6, IL-8, IL-10, INF-γ, GM-CSF and TNFα in D vs S and S compared with HV. Conclusions: Our analyses revealed distinct cytokine profiles and activated state of T cells in D cases suggests a contribution to the severity of disease during acute viral infection. These findings are in line with an active role of immune response in pathogenesis