Infection of Primary Human Monocytes by Epstein-Barr Virus

Abstract

Previous studies have reported that infection of monocytes by viruses such as cytomegalovirus and human immunodeficiency virus weakens host natural immunity. In the present study, we demonstrated the capability of Epstein-Barr virus (EBV) to infect and replicate in freshly isolated human monocytes. Using electron microscopy analysis, we observed the presence of EBV virions in the cytoplasm and nuclei of approximately 20% of monocytes. This was confirmed by Southern blot analysis of EBV genomic DNA sequences in isolated nuclei from monocytes. Infection of monocytes by EBV leads to the activation of the replicative cycle. This was supported by the detection of immediate-early lytic mRNA BZLF-1 transcripts, and by the presence of two early lytic transcripts (BALF-2, which appears to function in DNA replication, and BHRF-1, also associated with the replicative cycle). The late lytic BcLF-1 transcripts, which code for the major nucleocapsid protein, were also detected, as well as EBNA-1 transcripts. However, attempts to detect EBNA-2 transcripts have yielded negative results. Viral replication was also confirmed by the release of newly synthesized infectious viral particles in supernatants of EBV-infected monocytes. EBV-infected monocytes were found to have significantly reduced phagocytic activity, as evaluated by the quantification of ingested carboxylated fluoresceinated latex beads. Taken together, our results suggest that EBV infection of monocytes and alteration of their biological functions might represent a new mechanism to disrupt the immune response and promote viral propagation during the early stages of infection. Epstein-Barr virus (EBV), a member of theHerpesviridae family, has long demonstrated its capabilities to adapt and evade host defense mechanisms. While it was mainly believed that EBV infects only B cells and epithelial cells of the oropharynx, there is growing evidence that EBV targeted cells are broader than initially believed. In fact, recent studies have demonstrated that EBV can infect thymocytes, as revealed by the detection of BZLF-1 and EBV nuclear antigen (EBNA)-1

EBV Suppresses Prostaglandin E2 Biosynthesis in Human Monocytes

“…In the case of EBV, our laboratory first reported that a specific interaction between the virus and monocytes leads to a modulation of proinflammatory mediators such as induction of IL-1, IL-6, and leukotrienes (16,28), and suppression of TNF-␣ synthesis (29). More recently, we observed that EBV could replicate and establish a complete lytic cycle in freshly isolated monocytes (19). In the present study, we show that EBV suppresses PGE 2 biosynthesis in LPS-activated monocytes.…”

“…Moreover, levels of CD14 in infected cells remained comparable with those in control monocytes even after 24-and 48-h exposure to EBV at 37°C (Fig. 2, B and C), which allows expression of EBV viral genes in monocytes (19).…”

“…Moreover, our laboratory has previously shown that neutrophils are permissive to EBV viral entry and that EBV-infected neutrophils undergo premature cell death by apoptosis (18). More recently, we reported that EBV replicates in monocytes and reduces the ability of these cells to phagocytosis (19). Impairment of the phagocytosis machinery is likely to be advantageous for the viral outcome, because phagocytosis is involved in elimination of foreign organisms.…”

The EBV-Encoded dUTPase Activates NF-κB through the TLR2 and MyD88-Dependent Signaling Pathway

“…It is well established that EBV can productively infect monocytes and macrophages and that following infection there are changes in the expression of various cytokines/chemokines (22)(23)(24)48). It has been suggested that EBV induces the production of cytokines/chemokines in monocytes/macrophages by at least two distinct mechanisms (11,23), the first one is through the interaction of EBV envelope glycoproteins, such as gp350, with cellular receptors, and the second mechanism requires virus replication.…”

Deiminated Epstein‐Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis

“…Epstein-Barr virus (EBV), a member of the Herpesviridae family, is known to infect human B lymphocytes and epithelial cells of the oropharynx, establishing a reservoir in both of these cellular compartments (12). A large number of other cells may be infected in a transient manner (13)(14)(15).…”