Human Herpesvirus-6 Glycoprotein H and L Homologs Are Components of the gp100 Complex and the gH External Domain Is the Target for Neutralizing Monoclonal Antibodies

Liu, D.X.; Gompels, Ursula A.; Foà-Tomasi, Laura; Campadelli-Fiume, Gabriella

doi:10.1006/viro.1993.1562

Cited by 62 publications

(51 citation statements)

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“…The formation of a noncovalent gH:gL complex is apparently essential for the transport of gH to the cell surface. Similar gH:gL complexes have recently been observed in other herpes viruses such as human herpes virus-6 (Liu et al, 1993), human cytomegalovirus (Kaye et al, 1992) and pseudorabies virus (Klupp et al, 1994). It has recently been reported that VZV gH also forms a complex with the VZV gL (coded by gene 60), which has 19 % identity with gL of HSV (Davison & Scott, 1986).…”

Section: Varicella-zoster Virus (Vzv) Infection In Humans Causes Chicsupporting

confidence: 62%

Induction of varicella-zoster virus-neutralizing antibodies in mice by co-infection with recombinant vaccinia viruses expressing the gH or gL gene

Němečková¹,

Ludvı́ková

Marešová

et al. 1996

Journal of General Virology

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Recombinant vaccinia viruses (VV) expressing the varicella-zoster virus (VZV) glycoprotein H (gH) or glycoprotein L (gL) were constructed. The 94 kDa gH intermediate glycoprotein was synthesized in cell cultures infected with the VV-gH recombinant, but only coinfection with both recombinants resulted in the synthesis of the fully processed 118 kDa gH molecule. The W-expressed gH and gL formed a complex that displayed the conformational neutralization epitope detectable by means of human VZV gH-specific monoclonal antibody V3. Formation of this epitope was inhibited by tunicamycin but not by monensin. Simultaneous intraperitoneal inoculation of mice with high doses of both VV-gH and VV-gL viruses resulted in the development of VZV-neutralizing, complement-independent antibodies; these antibodies were not detected in mice infected solely with either the VV-gH or the VVgL recombinant.

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Section: Varicella-zoster Virus (Vzv) Infection In Humans Causes Chicsupporting

confidence: 62%

Induction of varicella-zoster virus-neutralizing antibodies in mice by co-infection with recombinant vaccinia viruses expressing the gH or gL gene

Němečková¹,

Ludvı́ková

Marešová

et al. 1996

Journal of General Virology

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“…Of these, gH and gL appear to play prominent roles in the membrane fusion events that initiate HHV-6 infectivity, based on inhibitory activities of specific antibodies (7)(8)(9)(10)(11)(12). As in other herpesviruses, these glycoproteins form a heterodimeric complex, with gL being required for correct folding, intracellular maturation, and surface expression of gH (9,(12)(13)(14)(15)(16).…”

Section: Human Herpesvirus 6 (Hhv-6)mentioning

confidence: 99%

“…The electrophoretic mobility of this protein is consistent with that reported for glycoprotein H (gH) (100 -110 kDa, Refs. 9,10,14).…”

Section: Hhv-6 Gh Binding To Cd46mentioning

confidence: 99%

“…We also examined the effects of depleting two other HHV-6 glycoproteins, gp82-gp105 and gB; all three glycoproteins are known to play critical roles in viral infectivity, as shown by the neutralizing activities of specific antibodies to gH (7)(8)(9)(10)(11)(12), gB (17), or gp82-gp105 (19). We first analyzed the products of direct immunoprecipitation from the lysate of a mixture of HHV-6-infected HSB-2 cells and CD46-expressing NIH 3T3 cells (Fig.…”

Section: Hhv-6 Gh Binding To Cd46mentioning

confidence: 99%

“…Of these, gH and gL appear to play prominent roles in the membrane fusion events that initiate HHV-6 infectivity, based on inhibitory activities of specific antibodies (7-12). As in other herpesviruses, these glycoproteins form a heterodimeric complex, with gL being required for correct folding, intracellular maturation, and surface expression of gH (9,(12)(13)(14)(15)(16). Moreover, gB (the most highly conserved glycoprotein among herpesviruses) and another glycoprotein, gp82-gp105, (thus far found only in HHV-6 and the related ␤-herpesvirus, HHV-7) appear to be critical for the fusion/entry process, as specific antibodies against these proteins block both virus infectivity and syncytia…”

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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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Human herpesvirus 6

Clark

2000

Rev. Med. Virol.

116

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Human herpesvirus 6 (HHV‐6), a member of the β‐herpesvirinae subfamily, is highly seroprevalent, has a worldwide distribution, and infection usually occurs within the first two years of life. In this age group, HHV‐6 causes febrile illness including exanthem subitum with seizures a recognised complication. The virus is predominantly T lymphotropic although it can infect a variety of cell types in vitro and CD46 has recently been identified as a cellular receptor. The virus persists in the host, with a latent state proposed in monocytes and bone marrow progenitor cells, and chronic infection in salivary glands. The virus is pathogenic in the post transplantation period and may be a cofactor in the progression of HIV disease. The virus has also been associated with multiple sclerosis (MS), with the virus detected in oligodendrocytes particularly in plaque regions. The role of HHV‐6 in MS remains controversial and a more extensive understanding of its neurotropism and association with disease is required. Two variants of HHV‐6 exist (A and B) and comparison of their complete nucleotide sequences shows the genomes to be colinear, with a high degree of homology. Variation in specific regions of the genome is more extensive and probably accounts for biological and pathological differences. Almost exclusively, variant B is associated with febrile illness in childhood and is the predominant variant detected in healthy individuals. The epidemiology of HHV‐6A infection needs to be better defined, although it is significantly less prevalent. Biological, genetic, epidemiological and pathological findings suggest that the two variants are divergent. Copyright © 2000 John Wiley & Sons, Ltd.

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Human Herpesvirus-6 Glycoprotein H and L Homologs Are Components of the gp100 Complex and the gH External Domain Is the Target for Neutralizing Monoclonal Antibodies

Cited by 62 publications

References 0 publications

Induction of varicella-zoster virus-neutralizing antibodies in mice by co-infection with recombinant vaccinia viruses expressing the gH or gL gene

Induction of varicella-zoster virus-neutralizing antibodies in mice by co-infection with recombinant vaccinia viruses expressing the gH or gL gene

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

Human herpesvirus 6

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