Abstract
BackgroundHuman herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS) and of some lymphoproliferative disorders of B cells. Most malignancies develop after long-lasting viral dormancy, and a preventing role for both humoral and cellular immune control is suggested by the high frequency of these pathologies in immunosuppressed patients. B cells, macrophages and dendritic cells of peripheral lymphoid organs and blood represent the major reservoir of HHV-8. Due to the dual role of B cells in HHV-8 infection, both as virus reservoir and as agents of humoral immune control, we analyzed the subset distribution and the functional state of peripheral blood B cells in HHV-8-infected individuals with and without cKS.Methodology/Principal FindingsCirculating B cells and their subsets were analyzed by 6-color flow cytometry in the following groups: 1- patients HHV-8 positive with classic KS (cKS) (n = 47); 2- subjects HHV-8 positive and cKS negative (HSP) (n = 10); 3- healthy controls, HHV-8 negative and cKS negative (HC) (n = 43). The number of B cells belonging to the preimmune/natural effector compartment, including transitional, pre-naïve, naïve and MZ-like subsets, was significantly higher among HHV-8 positive subjects, with or without cKS, while was comparable to healthy controls in the antigen-experienced T-cell dependent compartment. The increased number of preimmune/natural effector B cells was associated with increased resistance to spontaneous apoptosis, while it did not correlate with HHV-8 viral load.Conclusions/SignificanceOur results indicate that long-lasting HHV-8 infection promotes an imbalance in peripheral B cell subsets, perturbing the equilibrium between earlier and later steps of maturation and activation processes. This observation may broaden our understanding of the complex interplay between viral and immune factors leading HHV-8-infected individuals to develop HHV-8-associated malignancies.
Highlights
Human herpesvirus 8 (HHV-8) is a gammaherpesvirus etiologically linked to several malignancies such as Kaposi’s Sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic form of multicentric Castleman’s disease (MCD) [1,2,3]
In this study we characterized circulating B cells in patients with classic KS (cKS) to investigate whether Human herpesvirus-8 (HHV-8), which is the etiologic agent of Kaposi’s sarcoma (KS) and has tropism for many cell types including B cells, may affect the number and/or the immune phenotype of these cells
To avoid the confounding effects of other concomitant viral infections or immunosuppressive agents, we included in the study only patients with cKS and observed that B cells from these patients differ in many aspects from those of matched healthy controls (HC)
Summary
Human herpesvirus 8 (HHV-8) is a gammaherpesvirus etiologically linked to several malignancies such as Kaposi’s Sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic form of multicentric Castleman’s disease (MCD) [1,2,3]. According to the multifocal nature of KS, we recently demonstrated that circulating endothelial progenitor cells cultured from the peripheral blood of cKS patients are infected by HHV-8, support viral productive replication and may represent putative precursors of KS spindle cells [8]. Human herpesvirus-8 (HHV-8) is the etiological agent of Kaposi’s sarcoma (KS) and of some lymphoproliferative disorders of B cells. B cells, macrophages and dendritic cells of peripheral lymphoid organs and blood represent the major reservoir of HHV-8. Due to the dual role of B cells in HHV-8 infection, both as virus reservoir and as agents of humoral immune control, we analyzed the subset distribution and the functional state of peripheral blood B cells in HHV-8infected individuals with and without cKS
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