Comparison of Lymphocyte Populations in Patients With Dobrava or Puumala orthohantavirus Infection.

Katarina Resman Rus,Andreja Nataša Kopitar,Tatjana Avšič-Županc,Miša Korva,Alojz Ihan,Miroslav Petrovec

doi:10.3389/fcimb.2020.566149

Katarina Resman Rus, Andreja Nataša Kopitar + Show 4 more

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https://doi.org/10.3389/fcimb.2020.566149

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Abstract

Hemorrhagic fever with renal syndrome (HFRS), caused by Dobrava (DOBV) and Puumala (PUUV) orthohantaviruses, is an endemic disease in Slovenia. DOBV is mainly responsible for a more severe disease, whereas PUUV usually causes a milder form. Therefore, the aim of our study was to determine whether any differences in lymphocyte population in patients infected with these two viruses exist. Mononuclear cells from peripheral blood (PBMCs) were isolated from DOBV or PUUV infected patients and different lymphocyte subpopulations were analyzed with flow cytometry. Decreased concentrations of lymphocyte subpopulation were observed in DOBV and in PUUV infected patients compared with a healthy control, which was especially evident in DOBV infected patients. The lower values of T cells are likely due to the extravasation of the activated cells from the circulation to the infected tissue. Higher percentage of NK cells were detected in DOBV infected patients in comparison to PUUV infected patients, which could be associated with a more severe HFRS caused by DOBV. PUUV infected patients had a significantly higher concentration of activated T cell subsets, expressing markers CD25, CD69, and HLA-DR in comparison to DOBV infected patients. Higher activation of T cell subsets in PUUV infected patients could be a contributor to a milder HFRS. Further studies are necessary to elucidate the relation between the protective and the harmful role of activated lymphocytes subsets in HFRS pathogenesis.

Highlights

Orthohantaviruses cause two typical syndromes: hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS) in the Americas
Among Hemorrhagic fever with renal syndrome (HFRS) patients, 15 patients were infected with DOBV (14 males and 1 female) and 21 with Puumala virus (PUUV) (15 males and 6 females)
Viral antigens and different cytokines activate resting lymphocytes, that result in changes of the cell surface phenotype

Summary

Introduction

Orthohantaviruses cause two typical syndromes: hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. In Slovenia HFRS is caused by the Dobrava virus (DOBV) and the Puumala virus (PUUV). DOBV is mainly responsible for a more severe disease, whereas PUUV usually causes a milder form. The clinical severity of HFRS varies greatly and in Slovenia both a severe and a mild clinical course of the disease have been observed, with an overall case fatality rate of 4.5% (Avsic-Zupanc et al, 1999; Pal et al, 2005). The hallmark of HFRS is vascular permeability, which is probably caused by an excessive innate immune response, especially by pro-inflammatory cytokines, that affect barrier integrity (Terajima and Ennis, 2011)

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