Molecular Mechanisms of Interaction Between Human Immune Cells and Far Eastern Tick-Borne Encephalitis Virus Strains

Abstract

Although studies have established that immune mechanisms are important in controlling tick-borne encephalitis virus (TBEV) infection, the interactions of different TBEV strains with cells of innate and adaptive immunity are not well understood. In this study, the ability of two Far Eastern subtype TBEV strains (Dal'negorsk and Primorye-183) with various degrees of pathogenicity for humans to modulate the expression of membrane molecules differently on human immune cells were investigated using a whole-blood flow cytometry-based assay. The whole-blood samples (from 10 healthy donors) were infected with TBEV strains and analyzed for the virus binding to the blood cells, as well as expression of adhesion (CD11b and ICAM-1) and activation (CD69, CD25, CD95) molecules on the surfaces of monocytes, granulocytes, natural killer (NK) cells, and T-lymphocytes (CD4+, CD8+) at selected times (3, 6, and 24 h post-infection). It was found that the highly pathogenic Dal'negorsk strain penetrated rapidly and was actively replicated in the blood cells, inducing downregulation of CD11b, ICAM-1, and CD69 on monocytes and a significant decrease of NK cells expressing CD69, CD25, CD95, and CD8 T-lymphocytes expressing CD69 compared with the mock-infected cells. The nonpathogenic Primorye-183 strain penetrated slowly and was replicated in the blood cells, but caused a significant increase in the adhesion and activation of molecule expression to trigger innate defense mechanisms and enable the rapid elimination of the virus from the organism. Thus, TBEV-induced activation or suppression of adhesion and activation receptors expression form an essential part of fundamental virus properties, that is, virulence and pathogenicity.

Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity

“…Interestingly, ex vivo culture alone led to an increase in the basal expression level of CD69 in CD56 + CD94 + NK cells, as previously reported ( 49 ). Furthermore, ZIKV infection resulted in reduced levels of CD69, which is a phenomenon also reported for the flavivirus tick-borne encephalitis virus infection in healthy donor NK cells ( 50 ). Moreover, NK cells behave differently ex vivo and in vivo ( 51 ), which may explain the different levels of CD69 detected in patients and in ex vivo ZIKV-infected NK cells.…”

Zika virus infection preferentially counterbalances human peripheral monocyte and/or NK-cell activity

“…Interestingly, ex vivo culture alone led to an increase in the basal expression level of CD69 in CD56 + CD94 + NK cells, as previously reported (47). Furthermore, ZIKV infection resulted in reduced levels of CD69, which is a phenomenon also reported for the flavivirus tick-borne encephalitis virus infection in healthy donor NK cells (48). Moreover, NK cells behave differently ex vivo and in vivo (49), which may explain the different levels of CD69 detected in patients and in ex vivo ZIKV-infected NK cells.…”

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

“…Not only the TBEV subtype determines the severity of the disease. The relationship between the structure of the TBEV strains and their virulence or pathogenic properties had been shown for all three TBEV subtypes in both humans and mice [78, 173, 176–178]. Therefore, even if we assume that all patients involved in our study were infected with the same TBEV subtype, genetic variations in TBEV could affect the course of the disease.…”