Cutting Edge: Epstein-Barr Virus Transactivates the HERV-K18 Superantigen by Docking to the Human Complement Receptor 2 (CD21) on Primary B Cells

Abstract

EBV, a ubiquitous human herpesvirus, is the causative agent of infectious mononucleosis and is associated with many carcinomas. We have previously shown that the EBV latent genes LMP-1 and LMP-2A (for latent membrane proteins 1 and 2A), transactivate a human endogenous retrovirus (HERV), HERV-K18, in infected B lymphocytes. The envelope (Env) protein of HERV-K18 encodes a superantigen that strongly stimulates a large number of T cells. In this study we report that HERV-K18 env is transactivated even earlier in the infection process, before the establishment of latency; namely, we found that EBV, through its interaction with its cellular receptor CD21, induces the HERV-K18 env gene in resting B lymphocytes. This transactivation is direct and immediate, as up-regulation of transcripts can be detected within 30 min after EBV exposure. Thus, EBV binding to human CD21 on resting B cells triggers the expression of an endogenous superantigen. The biological significance of this superantigen expression for the EBV life cycle is discussed.

Expression of Human Endogenous Retrovirus Type K (HML-2) Is Activated by the Tat Protein of HIV-1

“…Although most HERV genes seem to be nonfunctional, there are some endogenous retroviral genes that are expressed, even becoming important contributors to human physiological processes, as can be seen in trophoblast development (2,34,44,80). However, HERV gene expression appears to be tightly controlled under normal circumstances, and only when cellular fitness or integrity is compromised (e.g., with synthetic chemical agents, radiation, stress, cytokines/chemokines, or biological agents acting upon human cells) is there pronounced or increased expression of endogenous retroviral elements (26,57,62,63,81,121,127). Under conditions where an exogenous virus, such as HIV-1, establishes a productive infection, the repression of HERV expression can be lifted (130).…”

“…However, in general, how or why HERV genes are expressed, and the mechanisms responsible for expression, is not clearly understood. It is known that exogenous viral infections, viral transactivators, processes such as inflammation, chemical agents, cytokines, hormones, and stress conditions can contribute to the activation and transcription of transposable genetic elements, HERV-K (HML-2) being an example (21,26,39,55,57,60,66,68,71,94,101,114,116,121,122,125,127). A possible role for HERV-K (HML-2) in pathogenesis has been considered in disorders such as systemic lupus erythematosus, rheumatoid arthritis, and neuroinflammation (3,36,43,53,77,90,112,113).…”

Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3

“…This "window" is when pathogens and BSAgs may have their greatest impact (90). We believe PRRSV is a pathogen that uses polyclonal B cell activation through a virus-derived or virus-stimulated BSAg (84) to subvert the normal development of adaptive immunity. This distraction causes a delay in the appearance of a protective antiviral response and, consequently, resolution of the infection.…”

The NP9 protein encoded by the human endogenous retrovirus HERV‐K(HML‐2) negatively regulates gene activation of the Epstein‐Barr virus nuclear antigen 2 (EBNA2)

“…For instance, a superantigen encoded by HERV-K18 env is induced in B-cells by EBV-infection. 19 The function of this superantigen for the viral life cycle remains to be elucidated.…”