Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease

Abstract

Retroviral diagnostics have become standard in human laboratory medicine. While current emphasis is placed on the human exogenous viruses (human immunodeficiency virus and human T-cell leukemia virus), evidence implicating human endogenous retroviruses (HERVs) in various human disease entities continues to mount. Literature on the occurrence of HERVs in human tissues and cells was analyzed. Substantial evidence documents that retrovirus particles were clearly demonstrable in various tissues and cells in both health and disease and were abundant in the placenta and that their occurrence could be implicated in some of the reproductive diseases. The characteristics of HERVs are summarized, mechanisms of replication and regulation are outlined, and the consistent hormonal responsiveness of HERVs is noted. Clear evidence implicating HERV gene products as participants in glomerulonephritis in some cases of systemic lupus erythematosus is adduced. Data implicating HERVs as etiologic factors in reproductive diseases, in some of the autoimmune diseases, in some forms of rheumatoid arthritis and connective tissue disease, in psoriasis, and in some of the inflammatory neurologic diseases are reviewed. The current major needs are to improve methods for HERV detection, to identify the most appropriate HERV prototypes, and to develop diagnostic reagents so that the putative biologic and pathologic roles of HERVs can be better evaluated.

Comparison Between Two Human Endogenous Retrovirus (HERV)-Rich Regions Within the Major Histocompatibility Complex

“…While HERVs within the MHC appear to be defective elements incapable of producing extracellular, infectious virions, they may still be transcriptionally and translationally active. They may influence immunity against exogenous retroviral infections and disease progression by inducing antibody responses to viral gene products, modifying the regulation of nearby cellular genes associated with immune responses, and competing for viral receptors on cell surfaces or for intracellular protein interactions (Lower et al 1996;Urnovitz and Murphy 1996). In this regard, HERV-16 (P5.1) has been reported to express mRNA in certain lymphoid cells and tissues (Vernet et al 1993b).…”

Retroelements and formation of chimeric retrogenes

“…They can be subdivided into two major groups: long terminal repeat (LTR)-containing elements and non-LTR retrotransposons. LTRs are usually 1000-1500-bp-long sequences flanking the retroelement 'body' in genomic DNA [12,13]. Autonomous non-LTR REs are generally assigned to LINEs (long interspersed nuclear elements).…”

“…The LTR promoter of EDNRB is used even more often than the normal one, and the APOC1 LTR-derived promoter initiates transcription of 15 % of endothelin receptor mRNAs. Furthermore, LR/ERV sequences in gene introns can be alternatively spliced [12,25,58,89,90]. In many cases LR/ERV sequences are included in constitutive gene exons and translated [12,25,58,91].…”

“…Furthermore, LR/ERV sequences in gene introns can be alternatively spliced [12,25,58,89,90]. In many cases LR/ERV sequences are included in constitutive gene exons and translated [12,25,58,91]. For instance, the fragment of the LR THE-1 element is a part of the human immunoglobulin heavy chain coding sequence [58].…”

Retroviral activity in Behçet's syndrome and systemic lupus erythematosus detected by a PCR-based reverse transcriptase assay

“…Systemic lupus erythematosus (SLE) is also an autoimmune multisystem in¯ammatory disease with variable course and prognosis but, in contrast to BS, is associated with the production of a range of autoantibodies [2]. Infectious agents have been implicated repeatedly in both disorders and, indeed, a viral cause was postulated in the description of BS by BehcË et himself [3,4,5,6,7].…”