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

Urnovitz, H B; Murphy, W H

doi:10.1128/cmr.9.1.72-99.1996

Cited by 14 publications

(18 citation statements)

References 52 publications

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“…31 Other infectious triggers, e.g. endogenous human retroviruses, have been implicated in psoriasis, 32 and retroviruses may also express superantigens. 33 The functional role of HLA-C is less well defined than that of the other class I HLA molecules.…”

Section: Discussionmentioning

confidence: 99%

HLA-Cw⊛0602 and HIV-associated psoriasis

Mallon¹,

Young²,

Bunce

et al. 1998

British Journal of Dermatology

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The aetiopathogenesis of psoriasis is unknown, but genetic and environmental factors may be involved. Psoriasis may not be one disease but a cutaneous inflammatory reaction pattern consequent upon several different independent or related stimuli in susceptible individuals. There are controversial issues regarding the immunological basis of psoriasis and the role of CD4 vs. CD8 T lymphocytes. Psoriasis has been associated with HLA-Cw6 and Cw7 by serology and specifically with HLA-Cw*0602 by polymerase chain reaction (PCR) typing. Psoriasis is probably no more common in HIV infection than in the general population; however, it may appear for the first time or pre-existing psoriasis may worsen and be difficult to treat in HIV disease. We have investigated the prevalence of HLA-C alleles, in the specific clinical context of HIV infection complicated by type 1 psoriasis, in a case control study of 14 men with HIV disease and type 1 psoriasis and 147 HIV-infected patients without psoriasis. Typing was performed using PCR with sequence-specific amplification primers. Eleven of 14 patients (79%) with psoriasis carried the HLA-Cw*0602 allele compared with 24.5% of those without psoriasis (odds ratio = 11.31; 95% confidence limits 2. 73 to 65.36; P = 0.0001). Two patients without the HLA-Cw*0602 allele carried instead the closely related Cw*0401/3 allele. The results confirm the previously reported association between the HLA-Cw*0602 allele and type 1 psoriasis, and suggest that the association with HLA-Cw*0602 is stronger in HIV-associated psoriasis although this trend needs to be supported by a larger sample. The immunodysregulation resulting from HIV infection may trigger psoriasis in those genetically predisposed by the Cw*0602 allele. As CD8 T cells recognize antigens in the context of class I major histocompatibility complex, the identification of an HLA class I association in HIV-associated psoriasis strengthens the argument for an important role for CD8 + T lymphocytes in the immunopathogenesis of psoriasis. Investigations of the pathogenesis of psoriasis should take account of clinical and other subtypes already identified.

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Section: Discussionmentioning

confidence: 99%

HLA-Cw⊛0602 and HIV-associated psoriasis

Mallon¹,

Young²,

Bunce

et al. 1998

British Journal of Dermatology

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“…At some point during evolution, exogenous (infectious) progenitors of HERVs inserted themselves into the cells of the germ line, where they have been replicated along with the host"s cellular genes following a Mendelian pattern [4,5]. Integration of endogenous retroviruses into the human germ line is thought to have occurred 2 to about 70 million years ago depending on the individual retrovirus and were introduced by mechanisms involving reverse transcription [3].…”

Section: Human Endogenous Retroviruses (Hervs)mentioning

confidence: 99%

“…A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 5 been shown to participate in the immunopathogenesis of MS [19] although adaptive immunity may predominate early in disease, reflected by selective T and B cell activation accompanying clinical relapses. Multiple groups have demonstrated that enhanced MHC class II expression on myeloid cells and accompanying innate immune activation are associated with damaged myelin and failure of re-myelination [20].…”

mentioning

confidence: 99%

Human endogenous retroviruses and multiple sclerosis: Innocent bystanders or disease determinants?

Antony

Deslauriers

Bhat

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

108

127

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Human endogenous retroviruses (HERVs) constitute 5-8% of human genomic DNA and are replication incompetent despite expression of individual HERV genes from different chromosomal loci depending on the specific tissue. Several HERV genes have been detected as transcripts and proteins in the central nervous system, frequently in the context of neuroinflammation. The HERV-W family has received substantial attention in large part because of associations with diverse syndromes including multiple sclerosis (MS) and several psychiatric disorders. A HERV-W-related retroelement, multiple sclerosis retrovirus (MSRV), has been reported in MS patients to be both a biomarker as well as an effector of aberrant immune responses. HERV-H and HERV-K have also been implicated in MS and other neurological diseases but await delineation of their contributions to disease. The HERV-W envelope-encoded glycosylated protein, syncytin-1, is encoded by chromosome 7q21 and exhibits increased glial expression within MS lesions. Overexpression of syncytin-1 in glia induces endoplasmic reticulum stress leading to neuroinflammation and the induction of free radicals, which damage proximate cells. Syncytin-1's receptor, ASCT1 is a neutral amino acid transporter expressed on glia and is suppressed in white matter of MS patients. Of interest, antioxidants ameliorate syncytin-1's neuropathogenic effects raising the possibility of using these agents as therapeutics for neuroinflammatory diseases. Given the multiple insertion sites of HERV genes as complete and incomplete open reading frames, together with their differing capacity to be expressed and the complexities of individual HERVs as both disease markers and bioactive effectors, HERV biology is a compelling area for understanding neuropathogenic mechanisms and developing new therapeutic strategies.

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“…2,3 Although full-length proviral transcripts have been detected in various normal and pathological human cells and tissues, most of them do not give rise to infectious viral particles as do exogenous retroviruses such as human immunodeficiency virus or human T-cell lymphotropic virus (HTLV), due to the presence of various point mutations and deletions. 2 However, in vitro studies have shown that these DNA proviruses are able to produce particles, suggesting that some copies have conserved their coding capacities. Recently, the transmissibility of such particles has been demonstrated for HERV-H ⁄ RGH-2, an endogenous retrovirus associated with multiple sclerosis.…”

mentioning

confidence: 99%