Retroviruses and Autoimmunity.

Abstract

The investigation of humanretroviruses has showndramatic progress since the discovery of human immunodeficiency virus (HIV). These studies have also contributed to the exploration of the role of retroviruses, including endogenous retroviruses, in the induction of autoimmune diseases such as systemic lupus erythematosus (SLE). This review describes the potential role of retroviruses in autoimmunity, based on recent findings including our own results. (Internal Medicine 40: 80-86, 2001)

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

“…HIV-1-infected individuals have abnormally high levels of the endogenous retrovirus HERV-K (HML-2) expressed in cells, and vastly increased RNA titers are present in their plasma (24,25,27,50,130). The conse-quences of this activation in the setting of HIV-1 infection are still a matter of speculation, but since HERV-K (HML-2) encodes two putative oncogenes and has been associated with several autoimmune, inflammatory, and neurological diseases, it could potentially participate in the development of HIV-1-associated disease (3,36,43,53,77,90,113). Understanding the initial steps in the activation of HERV-K (HML-2) expression after HIV-1 infection is the first step toward deciphering how HERV-K (HML-2) elements might play a role in HIV-1 pathogenesis.…”

“…The consequences of the high levels of HERV-K (HML-2) expression seen in HIV-1-infected individuals are potentially important, since increased expression of HERV-K has been associated with a number of different pathologies (3,18,36,43,53,54,113). HERV-K (HML-2) encodes the Rec protein, a Rev-like protein that could augment the transport of RNAs out of the nucleus (14,78,135), thus altering the global processing of cellular RNA.…”

“…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). Certain malignancies, most commonly germ cell tumors, melanoma, breast tumors, and prostate cancer, also show high levels of HERV-K (HML-2) antigen expression (18,59,62,104,110,132), sometimes accompanied by the production of viral particles (12,89), and yet the actual contribution of HERVs to disease remains to be characterized.…”

PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders

“…25 Exogenous and endogenous antigens are recognised by CD4 þ or CD8 þ T cells, respectively. In SLE, a decrease in the CD4/CD8 ratio can be observed that is due to an increase in the numbers of CD8 þ cells, [26][27][28] whereas for atopic dermatitis an increase in the CD4/CD8 ratio results from the expansion of CD4 þ cells. 29 It seems likely that the coexistence of two diseases dependent on differences in the CD4/CD8 ratio will be rare because the presence of one type of disease reduces the likelihood that the other develops.…”

Regulation of the Human Endogenous Retrovirus K (HML-2) Transcriptome by the HIV-1 Tat Protein

“…As expression of HERV-K (HML-2) transcripts and proteins has been associated with several cancers as well as autoimmune, inflammatory, and neurological conditions, the possibility of it participating in the development of HIV-1-associated disease or malignancies cannot be ruled out (54)(55)(56)(57)(58)(59)(60)(61). In fact, Np9 and Rec have been shown to be highly expressed in transformed tissues (Np9), to cause carcinoma in situ in mice (Rec), and to be associ-ated with the Notch pathway and pathways affecting c-myc expression (Np9 and both, respectively) (13,15,16,(62)(63)(64)(65).…”