Host-Level Susceptibility and IRF1 Expression Influence the Ability of IFN-γ to Inhibit KSHV Infection in B Lymphocytes.

in Viruses by Nedaa Alomari, Jennifer Totonchy

TLDR

  • The study found that IFN-γ can help prevent a virus called Kaposi's sarcoma-associated herpesvirus (KSHV) from infecting B cells in some people. The study found that IFN-γ works best in people who have certain characteristics that make them more susceptible to KSHV infection. The study also found that IFN-γ can help prevent the virus from infecting certain types of B cells called plasma cells. This suggests that IFN-γ can help prevent the virus from establishing itself in the body.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi's sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman's disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, little is known about the role of host microenvironment in the regulation of KSHV establishment in B cells. In the present study, we demonstrated that IFN-γ has a strong inhibitory effect on KSHV infection but only in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, and display increased levels of IRF1 and STAT1-pY701. The effect of IFN-γ in responsive samples was associated with increased frequencies of germinal center B cells (GCB) and decreased infection of plasma cells, suggesting that IFN-γ-mediated modulation of viral dynamics in GC can inhibit the establishment of KSHV infection.

Overview

  • The study investigates the role of host microenvironment in the regulation of Kaposi's sarcoma-associated herpesvirus (KSHV) establishment in B cells. The study focuses on the effect of interferon-gamma (IFN-γ) on KSHV infection in tonsil-derived lymphocyte samples. The hypothesis being tested is whether IFN-γ has a strong inhibitory effect on KSHV infection in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, and display increased levels of IRF1 and STAT1-pY701. The methodology used for the experiment includes the use of tonsil-derived lymphocyte samples, which were infected with KSHV and treated with IFN-γ. The study aims to answer the question of whether IFN-γ-mediated modulation of viral dynamics in germinal center B cells can inhibit the establishment of KSHV infection.

Comparative Analysis & Findings

  • The study found that IFN-γ has a strong inhibitory effect on KSHV infection in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, and display increased levels of IRF1 and STAT1-pY701. The effect of IFN-γ in responsive samples was associated with increased frequencies of germinal center B cells (GCB) and decreased infection of plasma cells, suggesting that IFN-γ-mediated modulation of viral dynamics in GC can inhibit the establishment of KSHV infection.

Implications and Future Directions

  • The study's findings suggest that IFN-γ-mediated modulation of viral dynamics in germinal center B cells can inhibit the establishment of KSHV infection. The study's findings have significant implications for the development of new therapies for KSHV-associated diseases. Future research directions could include the investigation of the role of other cytokines in the regulation of KSHV establishment in B cells and the development of targeted therapies that modulate the host microenvironment to inhibit KSHV infection.
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