An antibody- and synthetic peptide-defined rubella virus E1 glycoprotein neutralization domain

Wolinsky, Jerry S.; Sukholutsky, Elena; Moore, William T.; Lovett, Amy; McCarthy, Micheline; Adame, Barbara

doi:10.1128/jvi.67.2.961-968.1993

Cited by 41 publications

(21 citation statements)

References 49 publications

(60 reference statements)

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“…The functions of the RV E1 and E2 glycoproteins have been studied extensively. Using monoclonal antibodies, it has been shown that the E1 protein contains at least six nonoverlapping epitopes, some of which are associated with hemagglutination and neutralization (21,67,139,140,152,160,161). E1 appears to be the main surface protein, with domains involved in the attachment of the virus to the cell.…”

Section: E1 and E2 Glycoproteinsmentioning

confidence: 99%

Rubella Virus Replication and Links to Teratogenicity

2000

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SUMMARY Rubella virus (RV) is the causative agent of the disease known more popularly as German measles. Rubella is predominantly a childhood disease and is endemic throughout the world. Natural infections of rubella occur only in humans and are generally mild. Complications of rubella infection, most commonly polyarthralgia in adult women, do exist; occasionally more serious sequelae occur. However, the primary public health concern of RV infection is its teratogenicity. RV infection of women during the first trimester of pregnancy can induce a spectrum of congenital defects in the newborn, known as congenital rubella syndrome (CRS). The development of vaccines and implementation of vaccination strategies have substantially reduced the incidence of disease and in turn of CRS in developed countries. The pathway whereby RV infection leads to teratogenesis has not been elucidated, but the cytopathology in infected fetal tissues suggests necrosis and/or apoptosis as well as inhibition of cell division of critical precursor cells involved in organogenesis. In cell culture, a number of unusual features of RV replication have been observed, including mitochondrial abnormalities, and disruption of the cytoskeleton; these manifestations are most probably linked and play some role in RV teratogenesis. Further understanding of the mechanism of RV teratogenesis will be brought about by the investigation of RV replication and virus-host interactions.

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Section: E1 and E2 Glycoproteinsmentioning

confidence: 99%

Rubella Virus Replication and Links to Teratogenicity

2000

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“…RV contains three major antigens: the envelope glycoproteins (El and E2) and an internal capsid protein [11,12]. Four nonoverlapping domains that are binding sites for RV-neutralizing antibodies have been located within residues 213-285 on E1 [12,[14][15][16][17][18]. At least four T-cell antigenic sites within this sequence have also been mapped by using peripheral blood mononuclear cells (PBMNCs) or CD4 + T-cell lines in lymphoproliferation screening assays employing relatively long (16-33 aa) SPs [14,[19][20][21].…”

Section: Analysis Of Overlapping T-and B-cell Antigenic Sites On Rubementioning

confidence: 99%

Analysis of overlapping T- and B-Cell antigenic sites on rubella virus E1 envelope protein influence of HLA-DR4 polymorphism on T-cell clonal recognition

Mitchell

et al. 1994

Human Immunology

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A CTL antigenic site located between residues 273 and 291 of the E1 envelope protein of RV was identified by 51Cr-release assays employing SPs. Two E1-specific CTL clones were examined for immune recognition of RV wild-type and attenuated vaccine strains and recombinant E1 protein. The exact sequence (273-284) recognized by both clones was delineated by using truncated and overlapping SPs covering these residues. The defined T-cell site overlapped almost completely with a virus neutralizing antibody-binding site previously identified with mouse monoclonal and human antibodies. A series of single aa-substituted SP analogues of E1(273-284) was used to define residues critical for T-cell recognition. Using EBV-BL displaying different HLA-DR haplotypes and -DR4 subtypes as targets to determine MHC class II restriction elements, immune recognition by both T-cell clones was shown to be associated with HLA-DR4. Three HLA-DR4 subtypes (DR4Dw13A, DR4Dw13B, and DR4KT2) sharing a common residue, glutamic acid at position 74 in their beta 1 chains, were able to present SP E1(273-284) to the T-cell clones.

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“…a P values for comparisons between subjects whose sera exhibited a shift in immunoblot pattern from those subjects whose postvaccination sera exhibited no change in RV protein specificities as determined by IgG immunoblot assays. 239 (29,46), which is one of four known NT domains on this protein (8,40,43). GMTs and median antibody levels measured by the three whole-RV EIAs were determined to be well above their established negative cutoff points, suggesting that the majority of the individuals studied had protective levels of RV-specific IgG both before and after receiving the MMR vaccine.…”

Section: Discussionmentioning

confidence: 87%

“…RV has three major antigenic proteins: the envelope glycoproteins E1 and E2 and the internal capsid protein C. The protein most characterized biologically is E1, which contains four NT domains as well as the target sequence for HAI antibodies (8,40,43) located between amino acid residues 209 and 291. Synthetic peptides have been used to map one NT domain located between E1 residues 213 and 239 recognized by both murine and human antibodies (29).…”

mentioning

confidence: 99%

Rubella reimmunization: comparative analysis of the immunoglobulin G response to rubella virus vaccine in previously seronegative and seropositive individuals

Mitchell

Rogers

et al. 1996

J Clin Microbiol

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Rubella virus (RV)-specific immunoglobulin G (IgG) antibodies were studied in military recruits undergoing unselected immunization with live attenuated measles, mumps, and rubella virus (MMR) vaccine. Three different whole-RV enzyme immunoassays (EIAs) and an epitope-specific EIA with a synthetic peptide (BCH-178c) representing a neutralization domain on the RV E1 envelope protein were used. Before vaccination, 84.2, 87.7, and 84.5% of the subjects tested (n ‫؍‬ 399) were found to be seropositive (>10 IU/ml or assay equivalent) by the three whole-RV EIAs, respectively, while only 82.5% were seropositive by the BCH-178c EIA. Although prevaccination seropositivity rates were similar for the whole-RV EIAs (sensitivity, 94 to 100%), many sera considered seropositive by the whole-RV EIAs had E1 peptide EIA antibody levels of <10 IU/ml (sensitivity, 77.4 to 80.7%). One month after vaccination, 97.8, 97.2, and 93.5% of the subjects who were followed (n ‫؍‬ 356) were seropositive by the three whole-RV EIAs, respectively, while 89% had BCH-178c peptide-specific IgG titers of >10 IU/ml. After vaccination, depending on the assay used, up to 20.6% of initially seropositive individuals exhibited a greater than fourfold increase in RV-specific IgG, while up to 47.3% showed a greater than twofold increase. Increased antibody titers after vaccination (seroboosting) were most frequently associated with low levels of BCH-178c peptide-specific IgG before vaccination. RV protein-specific IgG was also studied by immunoblot assays in a subset (n ‫؍‬ 56) of individuals receiving the MMR vaccine. Of these, 89.4 and 91.1% exhibited RV protein (E1, E2, and C protein)-specific IgG before and after vaccination, respectively. Seroboosting (two-to fourfold increase in EIA titers of individuals seropositive by the whole-RV EIA before vaccination) was usually accompanied by a shift in the IgG immunoblot pattern from a single (E1) to multiple (E1-E1, E1-C, or E1-E2-C) specificities, suggesting exposure of new epitopes as a result of viral replication.

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An antibody- and synthetic peptide-defined rubella virus E1 glycoprotein neutralization domain

Cited by 41 publications

References 49 publications

Rubella Virus Replication and Links to Teratogenicity

Rubella Virus Replication and Links to Teratogenicity

Analysis of overlapping T- and B-Cell antigenic sites on rubella virus E1 envelope protein influence of HLA-DR4 polymorphism on T-cell clonal recognition

Rubella reimmunization: comparative analysis of the immunoglobulin G response to rubella virus vaccine in previously seronegative and seropositive individuals

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