Epstein-Barr virus infection-induced inflammasome activation in human monocytes

Abstract

Inflammasomes are cytoplasmic sensors that regulate the activity of caspase-1 and the secretion of interleukin-1β (IL-1β) or interleukin-18 (IL-18) in response to foreign molecules, including viral pathogens. They are considered to be an important link between the innate and adaptive immune responses. However, the mechanism by which inflammasome activation occurs during primary Epstein-Barr virus (EBV) infection remains unknown. Human B lymphocytes and epithelial cells are major targets of EBV, although it can also infect a variety of other cell types. In this study, we found that EBV could infect primary human monocytes and the monocyte cell line, THP-1, inducing inflammasome activation. We incubated cell-free EBV with THP-1 cells or primary human monocytes, then confirmed EBV infection using confocal microscopy and flow cytometry. Lytic and latent EBV genes were detected by real-time RT-PCR in EBV-infected monocytes. EBV infection of THP-1 cells and primary human monocytes induced caspase-dependent IL-1β production, while EBV infection of B-cell or T-cell lines did not induce IL-1β production. To identify the sensor molecule responsible for inflammasome activation during EBV infection, we examined the mRNA and the protein levels of NLR family pyrin domain-containing 3 (NLRP3), absent in melanoma 2 (AIM2), and interferon-inducible protein 16 (IFI16). Increased AIM2 levels were observed in EBV-infected THP-1 cells and primary human monocytes, whereas levels of IFI16 and NLRP3 did not show remarkable change. Furthermore, knockdown of AIM2 by small interfering RNA attenuated caspase-1 activation. Taken together, our results suggest that EBV infection of human monocytes induces caspase-1-dependent IL-1β production, and that AIM2, acting as an inflammasome, is involved in this response.

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

“…Viruses have been shown to evade AIM2 sensing possibly by inhibiting the ability of AIM2 to interact with released DNA. A recent study reported that Epstein–Barr virus (EBV) may activate AIM2 in THP1 cells . Two studies recently showed that influenza virus (IAV), a single stranded RNA virus, could trigger the release of endogenous DNA from damaged lung tissue possibly leading to AIM2 activation .…”

“…A recent study reported that Epstein-Barr virus (EBV) may activate AIM2 in THP1 cells. 79 Two studies recently showed that influenza virus (IAV), a single stranded RNA virus, could trigger the release of endogenous DNA from damaged lung tissue possibly leading to AIM2 activation. 80,81 One study stated that AIM2 dampened detrimental inflammation in the lung microenvironment of mouse infected with IAV and that AIM2-deficient mice had exacerbated immune responses to IAV.…”

Epstein Barr Virus Infection Affects Function of Cytotoxic T Lymphocytes in Patients with Severe Aplastic Anemia

“…Under auxiliary adhesion molecules, the antigen polypeptide can be recognized and combined by T cell receptor on the surface of CTLS, which gradually induces the production of toxic protein that ultimately kills the target cells. EBV can induce the secretion of IL-1, IL-6, and TNF- α by monocytes; contribute to the production and maturation of dendritic cells; and promote the proliferation of virus-specific CTLs [26, 27]. EBNA-1 is the only nuclear protein that is expressed in all infected cells.…”

Subclinical herpesvirus shedding among HIV-1-infected men on antiretroviral therapy

“…In contrast, we observed a modest trend for a positive correlation between EBV shedding rate and levels of plasma sCD14. EBV infection has been shown to play a role in inflammasome activation in monocytes, [47] so it is possible that higher rates of EBV shedding can lead to more activated monocytes. Indeed, our results showed the HIV(+) group had higher levels of sCD14 as well as higher rates of EBV shedding.…”