Immunity and retroviral superantigens in humans

doi:10.1016/S1471-4906(01)02146-9

Trends in Immunology

Volume 23, Issue 2, 1 February 2002, Pages 57-58

https://doi.org/10.1016/S1471-4906(01)02146-9 Get rights and content

Abstract

Several studies have suggested that some viruses use superantigens to modulate immune responses in humans. However, the identification and characterization of putative viral superantigens has proven to be very difficult. Two recent papers confirm the presence of an endogenous retroviral superantigen in humans, and show that its expression can be induced by secondary viral infections. The up-regulation of expression of endogenous retroviral superantigens has substantial implications for understanding the pathology of virus infections and human disease.

Section snippets

Evidence for viral superantigens?

The idea that human viruses express superantigens has been around for some time. However, initially promising leads with rabies virus, HIV, cytomegalovirus (CMV) and EBV (Table 1) failed subsequently to yield any definitive evidence. For example, one of the most exciting observations was that EBV infection of B cells induced the activation of human T cells expressing the Vβ13 element of the TCR [8]. This initial, Vβ-specific T-cell response then degenerated into a nonspecific response 48 hours

Viral superantigens and disease

These new findings reveal a novel connection between viral infection and the host immune response. Viral up-regulation of expression of host superantigen-encoding genes has the potential to affect dramatically the nature of the immune response generated, possibly nudging it into an autoimmune response in susceptible individuals [12]. For example, there has been much speculation that superantigens are potent activators of T cells that might cross-react with self-antigens [2]. Indeed, bacterial

Concluding remarks

The idea that viruses can activate endogenous superantigens is not in itself new. In mice, there is strong evidence that the BM5 murine leukemia virus complex activates endogenous MMTV genes [17]. However, the extension of this principle to humans has tremendous implications for viral pathology and human disease. It should be noted that EBV is an oncogenic virus and it is possible that the expression of endogenous superantigen(s) plays a role in tumor development. Originally, HERVs became fixed

Acknowledgements

I would like to thank Marcia Blackman and Linda Cauley for critical reading of the manuscript.

References (17)

J. Fraser
Superantigens – powerful modifiers of the immune system
Mol. Med. Today
(2000)
M.A. Blackman et al.
In vivo effects of superantigens
Life Sci.
(1995)
D. Dobrescu
Enhanced HIV-1 replication in Vβ12 T cells due to human cytomegalovirus in monocytes: evidence for a putative herpesvirus superantigen
Cell
(1995)
B. Conrad
A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes
Cell
(1997)
H. Acha-Orbea et al.
Superantigens of mouse mammary tumor virus
Annu. Rev. Immunol.
(1995)
N. Sutkowski
Epstein–Barr virus transactivates the human endogenous retrovirus HERV-K18 that encodes a superantigen
Immunity
(2001)
Y. Stauffer
Interferon-α-induced endogenous superantigen; a model link between environment and autoimmunity
Immunity
(2001)
L. Imberti
Selective depletion in HIV infection of T cells that bear specific T-cell receptor Vβ sequences
Science
(1991)

There are more references available in the full text version of this article.

Cited by (12)

Characterization of relapsing autoimmune encephalomyelitis and its treatment with decoy chemokine receptor genes
2005, Journal of Neuroimmunology
To elucidate the pathomechanisms of relapses of autoimmune disorders and to develop immunotherapy against relapses, we induced acute monophasic and chronic relapsing (CR) experimental autoimmune encephalomyelitis (EAE) in DA rats. Immunopathological and cytokine–chemokine analyses demonstrated that the number of infiltrating macrophages was significantly elevated in the CR-EAE than in acute EAE lesions and that IFN-γ and IP-10 in the spinal cord were significantly upregulated during the first attack and relapse of CR-EAE, respectively, than at the peak of acute EAE. In vivo administration of decoy chemokine receptor plasmid DNAs encoding the binding sites of CXCR3 and CCR2 suppressed the development of relapse of CR-EAE. Importantly, multiple injections of DNAs did not elicit the antibody production against chemokine receptors. Taken together, these findings demonstrated that neutralization therapy with decoy chemokine receptor DNAs is effective to control autoimmune diseases.
Allergic fungal sinusitis
2004, Otolaryngologic Clinics of North America
Staphylococcal enterotoxin B induces anergy to conventional peptide in memory T cells
2003, Cellular Immunology
Citation Excerpt :
Our data have implications for the better understanding of host–pathogen relationships. Superantigens may be encountered normally during infection, either as bacterial products or because viral infection may promote host cell surface expression of superantigens encoded by endogenous retroviruses [42,43]. Bacterial toxins have also recently been proposed as potential bioterrorism agents [42].
Microbial superantigens can alter host immunity through aberrant activation and subsequent anergy of responding naive T cells. We show here that the superantigen, staphylococcal enterotoxin B (SEB), directly induces tolerance in memory CD4 T cells. Murine naive and memory CD4⁺ T cells were labeled with the fluorescent dye CFSE and the cells were exposed to SEB before they were cultured with specific peptide antigen. Memory, but not naive, T cells became anergic and did not respond to their cognate peptide antigen. The extent and duration of T cell receptor (TCR) clustering was similar to promote naive T cell activation and memory T cell anergy, suggesting similar TCR–SEB interactions led to distinct intracellular signaling processes in the two cell types. Like SEB, soluble anti-CD3 mAb does not stimulate memory cell proliferation. However, unlike SEB, soluble anti-CD3 mAbs did not induce anergy to cognate peptide. Anergy was directly visualized in vivo. CD4⁺ memory T cells were identified in mice that had been administered SEB. The cells failed to proliferate in response to subsequent immunization with their cognate recall antigen. Hence, one mode of pathogen survival is the modulation of host immunity through selective elimination of memory T cell responses.
Human viral superantigens: To be or not to be transactivated?
2002, Trends in Immunology
Human RNA "rumor" viruses: The search for novel human retroviruses in chronic disease
2008, Microbiology and Molecular Biology Reviews
McAlpine's Multiple Sclerosis
2006, McAlpine's Multiple Sclerosis

View all citing articles on Scopus

View full text

Article preview

Trends in Immunology

Abstract

Section snippets

Evidence for viral superantigens?

Viral superantigens and disease

Concluding remarks

Acknowledgements

References (17)

Superantigens – powerful modifiers of the immune system

Mol. Med. Today

In vivo effects of superantigens

Life Sci.

Enhanced HIV-1 replication in Vβ12 T cells due to human cytomegalovirus in monocytes: evidence for a putative herpesvirus superantigen

Cell

A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes

Cell

Superantigens of mouse mammary tumor virus

Annu. Rev. Immunol.

Epstein–Barr virus transactivates the human endogenous retrovirus HERV-K18 that encodes a superantigen

Immunity

Interferon-α-induced endogenous superantigen; a model link between environment and autoimmunity

Immunity

Selective depletion in HIV infection of T cells that bear specific T-cell receptor Vβ sequences

Science

Cited by (12)

Characterization of relapsing autoimmune encephalomyelitis and its treatment with decoy chemokine receptor genes

Allergic fungal sinusitis

Staphylococcal enterotoxin B induces anergy to conventional peptide in memory T cells

Human viral superantigens: To be or not to be transactivated?

Human RNA "rumor" viruses: The search for novel human retroviruses in chronic disease

McAlpine's Multiple Sclerosis

Trends in Immunology

Research updateImmunity and retroviral superantigens in humans

Abstract

Section snippets

Evidence for viral superantigens?

Viral superantigens and disease

Concluding remarks

Acknowledgements

Mol. Med. Today

Life Sci.

Cell

Cell

Superantigens of mouse mammary tumor virus

Annu. Rev. Immunol.

Epstein–Barr virus transactivates the human endogenous retrovirus HERV-K18 that encodes a superantigen

Immunity

Interferon-α-induced endogenous superantigen; a model link between environment and autoimmunity

Immunity

Selective depletion in HIV infection of T cells that bear specific T-cell receptor Vβ sequences

Science

Research update
Immunity and retroviral superantigens in humans