Article

Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Monocytes Downregulates Expression of Adaptive Immune Response Costimulatory Receptors and Proinflammatory Cytokines

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Journal of Virology (Impact Factor: 4.65). 01/2012; 86(7):3916-23. DOI: 10.1128/JVI.06437-11
Source: PubMed

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) infection is associated with the development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. We report the establishment of a monocytic cell line latently infected with KSHV (KSHV-THP-1). We profiled viral and cytokine gene expression in the KSHV-THP-1 cells compared to that in uninfected THP-1 cells and found that several genes involved in the host immune response were downregulated during latent infection, including genes for CD80, CD86, and the cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Thus, KSHV minimizes its immunological signature by suppressing key immune response factors, enabling persistent infection and evasion from host detection.

Download full-text

Full-text

Available from: Dirk P Dittmer, Aug 18, 2015
0 Followers
 · 
144 Views
  • Source
    • "Previous studies by our group demonstrate that HHV-8 infection of MDDC in vitro reduces their level of endocytosis as well as inhibits their ability to activate virus-specific CD8 + T cells (Rappocciolo et al., 2006a). In addition, Gregory et al. (2012) established latent HHV-8 infection of a monocyte cell line in vitro as a model to study the impact of HHV-8 on monocyte function. Latent viral infection of the monocyte cell line was associated with a dampened inflammatory and adaptive immune response, indicated by a decrease in proinflammatory cytokine production and monocyte co-stimulatory molecule expression associated with T cell activation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Human herpesvirus 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is an oncogenic gammaherpesvirus that primarily infects cells of the immune and vascular systems. HHV-8 interacts with and targets professional antigen presenting cells and influences their function. Infection alters the maturation, antigen presentation, and immune activation capabilities of certain dendritic cells (DC) despite non-robust lytic replication in these cells. DC sustains a low level of antiviral functionality during HHV-8 infection in vitro. This may explain the ability of healthy individuals to effectively control this virus without disease. Following an immune compromising event, such as organ transplantation or human immunodeficiency virus type 1 infection, a reduced cellular antiviral response against HHV-8 compounded with skewed DC cytokine production and antigen presentation likely contributes to the development of HHV-8 associated diseases, i.e., Kaposi's sarcoma and certain B cell lymphomas. In this review we focus on the role of DC in the establishment of HHV-8 primary and latent infection, the functional state of DC during HHV-8 infection, and the current understanding of the factors influencing virus-DC interactions in the context of HHV-8-associated disease.
    Frontiers in Microbiology 08/2014; 5:452. DOI:10.3389/fmicb.2014.00452 · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Innate immunity represents the foremost barrier to viral infection. In order to infect a cell efficiently, viruses need to evade innate immune effectors such as interferons and inflammatory cytokines. Pattern recognition receptors can detect viral components or pathogen-associated molecular patterns. These receptors then elicit innate immune responses that result in the generation of type I interferons and proinflammatory cytokines. Organized by the Society for General Microbiology, one session of this conference focused on the current state-of-the-art knowledge on innate barriers to infection of different RNA and DNA viruses. Experts working on innate immunity in the context of viral infection provided insight into different aspects of innate immune recognition and also discussed areas for future research. Here, we provide an overview of the session on innate barriers to infection.
    Future Microbiology 07/2012; 7(7):815-22. DOI:10.2217/fmb.12.52 · 3.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Kaposi's sarcoma-associated herpesvirus (KSHV) infection is correlated with three human malignancies and can establish lifelong latent infection in multiple cell types within its human host. In order to establish and maintain infection, KSHV utilizes multiple mechanisms to evade the host immune response. One such mechanism is the expression of a family of genes with homology to cellular interferon regulatory factors (IRFs), known as viral IRFs (vIRFs). We demonstrate that KSHV vIRF1, 2, and 3 have a differential ability to block type I interferon signaling mediated by Toll-like Receptor 3 (TLR3), a receptor we have previously shown to be activated upon KSHV infection. vIRF1, 2, and 3 inhibited TLR3-driven activation of interferon (IFN) transcription reporters. However, only vIRF1 and 2 inhibited increases in both IFNβ message and protein following TLR3 activation. Expression of vIRF1 and vIRF2 also allowed for increased replication of a virus known to activate TLR3 signaling. Furthermore, vIRF1 and vIRF2 may block TLR3-mediated signaling via different mechanisms. Together, this report indicates that vIRFs are able to block IFN mediated by TLRs, but that each vIRF has a unique function and mechanism to block antiviral IFN responses.
    Journal of Virology 10/2012; · 4.65 Impact Factor
Show more