The human non‐lineage antigen CD46 (HuLy‐m5) and primate retroviral gp70 molecules share protein‐defined antigenic determinants

Purcell, DF; Deacon, Nicholas J.

doi:10.1038/icb.1989.42

Cited by 11 publications

(5 citation statements)

References 22 publications

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“…The following mAbs against human CD46 were used (at 25 g/ml): J4.48 (25) and E4.3 (26) to SCR1, purchased from Beckman Coulter, Fullerton, CA and Santa Cruz Biotechnology, Santa Cruz, CA, respectively; mAbs M177 to CD46 SCR2 and M160 to CD46 SCR3 (27), kindly provided by Tsukasa Seya, Osaka Medical Center, Osaka, Japan; and mAb GB24, which recognizes SCR4 (Ref. 28 and unpublished data).…”

Section: Methodsmentioning

confidence: 99%

Interaction of Glycoprotein H of Human Herpesvirus 6 with the Cellular Receptor CD46

Santoro

Greenstone

Insinga³

et al. 2003

Journal of Biological Chemistry

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Human herpesvirus 6 (HHV-6) employs the complement regulator CD46 (membrane cofactor protein) as a receptor for fusion and entry into target cells. Like other known herpesviruses, HHV-6 encodes multiple glycoproteins, several of which have been implicated in the entry process. In this report, we present evidence that glycoprotein H (gH) is the viral component responsible for binding to CD46. Antibodies to CD46 co-immunoprecipitated an ϳ110-kDa protein band specifically associated with HHV-6-infected cells. This protein was identified as gH by selective depletion with an anti-gH monoclonal antibody, as well as by immunoblot analysis with a rabbit hyperimmune serum directed against a gH synthetic peptide. In reciprocal experiments, a monoclonal antibody against HHV-6 gH was found to co-immunoprecipitate CD46. Studies using monoclonal antibodies directed against specific CD46 domains, as well as engineered constructs lacking defined CD46 regions, demonstrated a close correspondence between the CD46 domains involved in the interaction with gH and those previously shown to be critical for HHV-6 fusion (i.e. short consensus repeats 2 and 3).Human herpesvirus 6 (HHV-6) 1 is a member of the ␤-herpesvirus subfamily (reviewed in Ref. 1). Two major HHV-6 variants, A and B, have been defined that form two segregated clusters with unique genetic, biologic, and immunologic characteristics. Primary infection with HHV-6 B occurs almost universally in early childhood and has been etiologically linked to exanthema subitum. In adult life, HHV-6 infection and/or reactivation have been associated with a wide range of diseases, including multiple sclerosis, but most of these associations have yet to be substantiated by rigorous epidemiological studies. In immunocompromised people, including those infected with human immunodeficiency virus, HHV-6 B has been implicated as an opportunistic agent that may cause life-threatening respiratory tract and central nervous system infections, as well as bone marrow or organ graft failure. Moreover, HHV-6 may act as a cofactor to accelerate progression of human immunodeficiency virus disease.The best studied members of the herpesvirus family enter cells by direct fusion with the plasma membrane in a process involving binding of viral glycoproteins to specific protein receptors on the target cell (reviewed in Ref.2). Fusion is also facilitated by virus interactions with cell surface glycosaminoglycans. Recently, we identified CD46 (membrane cofactor protein) as a cellular receptor mediating fusion and entry for both HHV-6 variants (3). This glycoprotein also serves as a cellular receptor mediating critical events in the infectious process of other human pathogens, including binding/fusion/ entry of measles virus, pilus binding of different pathogenic Neisseriae, and adhesion of group A Streptococci (reviewed in Ref. 4). CD46 is a member of the regulators of complement activation (RCA) protein family. It is a type I transmembrane glycoprotein of 45-67 kDa, expressed on most or all human nucleated ce...

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Section: Methodsmentioning

confidence: 99%

Interaction of Glycoprotein H of Human Herpesvirus 6 with the Cellular Receptor CD46

Santoro

Greenstone

Insinga³

et al. 2003

Journal of Biological Chemistry

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“…Polymorphisms have been noted in other members of the complement regulatory family, as CD55 has cytoplasmic tails generated by alternative splicing [21], and CD3S has a polymorphic variation in the number of SCR units [22]. In this study we examined CD46 protein and R N A using different tissues from a single donor and the same tissues from different donors.…”

Section: Discussionmentioning

confidence: 99%

Tissue‐specific and allelic expression of the complement regulator CD46 is controlled by alternative splicing

1992

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CD46 (membrane cofactor protein) is a human cell surface glycoprotein with cofactor activity for factor I-mediated cleavage of complement components C3b and C4b. The CD46 protein from normal lymphocytes resolves on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as two major bands of 66 and 56 kDa. CD46 cDNA encodes four extracellular short consensus repeat domains, a Ser/Thr/Pro (STP)-rich region, a transmembrane region and a cytoplasmic tail. We now show that exquisite control of mRNA splicing is responsible for the heterogeneous expression of CD46 isoforms. Differential splicing of 5 exons generates at least 14 CD46 mRNA variants whose expression is stringently regulated by allelic, tissue-specific and malignancy-related factors, as: (a) leukemic cells and Epstein-Barr virus-transformed B cells preferentially incorporate the first of three STP exons (exon 7) into mRNA, and produce a larger CD46 isoform of 74 kDa, (b) an allelic difference in the proportion of 66- and 56-kDa CD46 isoforms on lymphocytes corresponds to the preferential inclusion or exclusion of the second STP exon (exon 8), (c) the third STP exon (exon 9) is specifically deleted in some placentae, (d) spermatozoa delete both exons 12 and 13, encoding a shorter transmembrane region and a unique cytoplasmic tail and (e) all tissues tested differentially splice exon 13, resulting in two alternative cytoplasmic tails. The distribution of the 14 alternatively spliced RNA transcripts correlated with the presence of protein isoforms of the predicted size, indicating that alternative splicing leads to heterogeneity of CD46 glycoproteins.

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“…Skin in atopic dermatitis, especially after epi cutaneous allergen patch testing, shows an additional ex pression of such epitopes. It remains to be established whether this expression reflects the presence of as yet un known endogenous retroviral(-Iikc) elements [7][8][9], or represents molecular mimicry of conformational epitopes shared by viral and host molecules [10][11][12][13]. Fundamental studies on this aspect may broaden the present insight in host-retrovirus interactions.…”

Section: Discussionmentioning

confidence: 99%

“…It was hypothesized that the binding can be ascribed to the expression of as yet unknown endogenous retroviral(-like) elements [7][8][9], or on molecular mimicry of conformational epitopes shared by viral and host molecules [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Epitopes of Human Immunodeficiency Virus Regulatory Proteins Tat,Nef and Rev are Expressed in Skin in Atopic Dermatitis

Schuurman¹,

Joling²,

Wichen³

et al. 1993

Int Arch Allergy Immunol

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We extend our previous documentation that epitopes of HIV regulatory proteins tat, rev, and nef are expressed in tissue from uninfected individuals by the immunohistochemical analysis of normal skin (n = 10) and skin in some selected inflammatory dermatoses including urticaria (n = 6), systemic lupus erythematosus (n = 6), and atopic dermatitis (affected skin, n = 10, and after epicutaneous patch test for allergens, n = 8). A rabbit antibody to HIV-2 tat did not show immunolabeling of skin. Blood vessel endothelium was immunolabeled by one of two antibodies applied to HIV-1 tat, by an antibody to HIV-1 rev, and by two antibodies to HIV-1 nef. In addition one of the anti-nef antibodies labeled Langerhans cells. The anti-rev antibody labeled Langerhans cells and melanocytes in the epidermis, and dendritic cells in the dermis. The labeling of these skin components did not differ in prevalence between controls and groups of dermatoses. For other components, diseased skin conditions especially atopic dermatitis showed additional labeling. In affected skin, keratinocytes were labeled by antibodies to rev and one of two antibodies to nef. Skin after epicutaneous allergen patch testing also showed a statistically significantly increased prevalence of immunolabeling of dendritic cells and Langerhans cells by one of the anti-tat antibodies. We conclude that skin components show expression of epitopes recognized by antibodies to HIV-1 tat, rev, and nef; this expression is more extensive in atopic dermatitis than in normal skin, and can be further increased after epicutaneous allergen patch testing. This indicates that inflammatory conditions are associated with upregulation of molecules that share epitopes with HIV-1 regulatory proteins. In the immunohistochemical approach to study regulation of HIV-1 expression in tissue, the presently available antibodies cannot be used. In particular, this concerns tissue in a state of inflammation.

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The human non‐lineage antigen CD46 (HuLy‐m5) and primate retroviral gp70 molecules share protein‐defined antigenic determinants

Cited by 11 publications

References 22 publications

Interaction of Glycoprotein H of Human Herpesvirus 6 with the Cellular Receptor CD46

Interaction of Glycoprotein H of Human Herpesvirus 6 with the Cellular Receptor CD46

Tissue‐specific and allelic expression of the complement regulator CD46 is controlled by alternative splicing

Epitopes of Human Immunodeficiency Virus Regulatory Proteins <i>Tat</i><i>,</i><i>Ne</i><i>f</i> and <i>Rev</i> are Expressed in Skin in Atopic Dermatitis

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