Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor Function

Greenstone, Heather L.; Santoro, Fabio; Lusso, Paolo; Berger, Edward A.

doi:10.1074/jbc.m206488200

Cited by 61 publications

(49 citation statements)

References 55 publications

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“…Using complementary co-immunoprecipitation approaches, we identified the gH glycoprotein as the CD46-binding component of HHV-6. Mapping studies demonstrated that the CD46 determinants critical for gH binding reside in SCR2 and SCR3, consistent with our previous study (5) indicating the importance of the same CD46 domains for HHV-6 fusion.…”

Section: Human Herpesvirus 6 (Hhv-6)supporting

confidence: 74%

“…Flow cytometry analysis confirmed equivalent expression of all constructs (Ref. 5 and data not shown). As shown in Fig.…”

Section: Fig 2 Immunodepletion Of Gh Abrogates Cd46 Co-precipitatiomentioning

confidence: 90%

“…Virus and Infection Procedure-HHV-6 variant A (strain GS) was first propagated in adult human PBMC followed by co-culturing with HSB-2 cells as described (5). Briefly, 20 ϫ 10 6 PBMC were cultured for 3 days at 2 ϫ 10 6 cells/ml in RPMI-10 plus 5 g/ml of phytohemagglutinin (Sigma).…”

Section: Methodsmentioning

confidence: 99%

“…The immunoprecipitates were analyzed by immunoblotting with antiserum against gH. Bolded SCRs indicate domains previously shown to be required for HHV-6 fusion to target cells (5). Shading denotes domains derived from DAF.…”

Section: Fig 2 Immunodepletion Of Gh Abrogates Cd46 Co-precipitatiomentioning

confidence: 99%

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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: Human Herpesvirus 6 (Hhv-6)supporting

confidence: 74%

“…Flow cytometry analysis confirmed equivalent expression of all constructs (Ref. 5 and data not shown). As shown in Fig.…”

Section: Fig 2 Immunodepletion Of Gh Abrogates Cd46 Co-precipitatiomentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Fig 2 Immunodepletion Of Gh Abrogates Cd46 Co-precipitatiomentioning

confidence: 99%

See 2 more Smart Citations

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

Santoro

Greenstone

Insinga³

et al. 2003

Journal of Biological Chemistry

Self Cite

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“…[38][39][40] HHV-6 is the only known herpesvirus that utilizes CD46 for infection and entry into the host cell. [41][42][43][44] Interestingly, a higher expression of CD46 is observed on the surface of untreated CB cells compared with G-CSF-mobilized hematopoietic progenitor cells used in HSCT, which may contribute to the increased prevalence of post-CBT HHV-6 reactivation. 10,45,46 However, several lines of evidence suggest that other cellular factors in addition to CD46 are crucial to the establishment of active HHV-6 infection in vivo.…”

Section: Discussionmentioning

confidence: 99%

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

Scheurer

Pritchett

Amirian

et al. 2012

Bone Marrow Transplant

108

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Reactivation of human herpesvirus-6 (HHV-6) frequently occurs following hematopoietic SCT (HSCT), and has been associated with clinical consequences in many patient populations. HHV-6 reactivation and HHV-6 encephalitis seem to occur more frequently in patients undergoing HSCT with cord blood (CB) as the stem cell source. We have conducted a systematic literature review and meta-analysis to investigate the clinical significance of this correlation. A systematic review of publications indexed in PubMed was performed for HSCT studies published over the past 10 years that fit inclusion criteria. Data on prevalences of HHV-6 reactivation and HHV-6 encephalitis post HSCT were abstracted from 19 papers. Meta-analyses were conducted to calculate combined prevalence estimates. The prevalences of HHV-6 reactivation and encephalitis were compared among CB vs non-CB HSCT. Prevalences of HHV-6 reactivation and HHV-6 encephalitis were significantly higher in patients receiving CB as the stem cell source than in patients receiving another stem cell source (72.0% vs 37.4%, Po0.0001; 8.3% vs 0.50%, Po0.0001, respectively). HHV-6 reactivation and HHV-6 encephalitis are significant complications in the post-HSCT setting, particularly in patients receiving CB as the stem cell source. Thus, patients undergoing umbilical CB transplantation should be closely monitored for HHV-6 reactivation.

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Interactions of Virus and Host

Neill¹

2005

Bovine Viral Diarrhea Virus

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Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor Function

Cited by 61 publications

References 55 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

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

Interactions of Virus and Host

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