Detection of human papillomavirus capsid antigens in various squamous epithelial lesions using antibodies directed against the L1 and L2 open reading frames

Firzlaff, J M; Kiviat, Nancy B.; Beckmann, Anna Marie; Jenison, Steven; Galloway, Denise A.

doi:10.1016/0042-6822(88)90561-2

Cited by 54 publications

(35 citation statements)

References 37 publications

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“…Our ultrastructural studies are consistent with this hypothesis; within the nucleus, the E4 protein appears to be organized into regular arrays that have the appearance of viral particles, but with a diameter less than that of an intact viral capsid, which is 55 nm (52). Of note, however, Li and L2 gene expression are not necessarily linked to E4 expression, because in contrast to our finding that E4 expression often occurs in high grade CIN, most cases of high grade CIN are not found to contain the LI and L2 proteins (14). Further studies will be needed, however, to determine the significance ofthese findings for the function ofthe E4 protein, the significance of its loss of expression in cervical cancer, and the prognostic implications of the detection of the protein in normal tissues.…”

Section: Discussioncontrasting

confidence: 54%

“…Previous studies have shown that E4 mRNA in CIN containing HPV 16 DNA is also found in the same epithelial cell strata (22). Similarly, late region protein expression occurs in the upper cell layers of the epithelium (14). One interpretation of these findings is that HPV gene expression is linked to cell differentiation, since the middle and superficial layers of the epithelium contain cells that are more differentiated than cells comprising the basal layer.…”

Section: Discussionmentioning

confidence: 90%

“…The latter can encode the LI and L2 proteins which are thought to be the major and minor capsid proteins, respectively; these are believed to be expressed only in productive viral infection (14). The E region proteins El and E2 are important in viral transcriptional regulation (15)(16)(17), whereas the E6 and E7 proteins are thought to be more directly involved in malignant transformation, with the latter playing the major role (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.

Palefsky

Winkler²,

Rabanus³

et al. 1991

J. Clin. Invest.

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The role of human papillomavirus (HPV) proteins in the pathogenesis ofcervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN 1 to CIN 3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 pro-

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.

Palefsky

Winkler²,

Rabanus³

et al. 1991

J. Clin. Invest.

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“…Other than BPV-1-and BPV-2-induced fi bropapillomas in cattle and HPV-l-induced plantar warts in humans, productive PV in fections do not produce the quantity of re coverable virions necessary to determine the feasibility of developing capsid proteinbased antigen detection systems for the var ious PVs, particularly HPV. However, rec ombinant DNA technology has provided the opportunity to use bacterially expressed PV MCP and minor capsid proteins for screen ing human sera for HPV antibodies as well as producing antibodies in rabbits and mice to HPV capsid protein [20][21][22][23]. Unfortunately, the significance of reactivity of human and animal sera with the fusion proteins encoded by various H PV DN A constructions is uncer tain, in part, because of the paucity of infor mation known about the natural response of the human immune system to viral specific epitopes present on either virions or appro priate fusion proteins.…”

Section: Discussionmentioning

confidence: 99%

Bovine Serological Response to a Recombinant BPV-1 Major Capsid Protein Vaccine

Jin

Cowsert²,

Marshall³

et al. 1990

Intervirology

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Four of five groups of Holestine by Angus calves (5 calves/group) were immunized with different formulations of a recombinant BPV-1 DNA vaccine using a BPV-1 major capsid: B-galactosidase fusion protein as the immunogen. Group 5 was not vaccinated. Vaccinated calves received the vaccine on days 0 and 21 of the trial, and calves from all five groups were challenged intradermally with 10¹⁰ BPV-1 particles at each of two different sites on day 56. All calves were bled on days 3, 24, 55, 77, and 104 of the trial, and the sera were tested for reactivity with intact and disrupted BPV-1 particles by ELISA. At the time of challenge with BPV-1 virions (day 56), 19 of 20 vaccinated calves were seropositive for disrupted BPV-1 particles; sera from 3 of 20 calves reacted with intact BPV-1 virions. By day 77,11 of 19 vaccinated calves had developed antibody titers to intact BPV-1 virions; only 1 calf in group 5 developed antibodies (transiently) against BPV-1 capsid epitopes. After challenge, 24 of 25 calves from the five groups developed intradermal fibromas, the biological end point of this study. Fibromas appeared to increase in size in group 5 (unvaccinated, inoculated controls), whereas most tumors from the four vaccinated groups (1–4) stabilized or decreased in size. Although the calves developed fibromas, 90% of calves (in groups 1–4) developed antibodies against disrupted BPV-1 capsid proteins whereas 58% developed antibodies that reacted with intact virions. The immunologic response of vaccinated calves to intact and disrupted BPV-1 particles appeared to be determined in large part by the various formulations of the vaccine, particularly the adjuvant.

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“…As will be evident, such responses may or may not be duplicated by exposure to wild-type virus in vivo. The principal studies of type-specific immune reagents focus on the late proteins, which are components of the viral capsid and which share considerable cross-homology among both animal papillomaviruses and HPVs (6,49 anti-L2 antibodies that cross-reacted with more than one HPV fusion protein type on Western blot appeared type specific in immunohistochemical analyses (36). The reasons for this disparity in reactivity are unclear, but these observations indicate the importance of the method used and target preparation.…”

Section: Characterization Of the Immune Response To Genital Hpvsmentioning

confidence: 99%

Pathobiology of papillomavirus-related cervical diseases: prospects for immunodiagnosis

1991

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In recent years, the relationship between human papillomaviruses (HPV) and genital neoplasia has been explored intensively, and a molecular basis for the role of HPV in the genesis of these diseases has been convincingly demonstrated. These findings have provided justification for efforts to apply this molecular information to the early detection and possible prevention of HPV-related neoplasia. The technology of detecting viral nucleic acids in genital fluids brought with it initial hopes that it would serve to identify women at risk for having or developing precancers or cancers of the cervix. Subsequent studies, however, have demonstrated limitations of the technology for predicting future disease. Recently, molecular immunology has complemented these prior efforts, with the intent to identify serological indices of exposure to HPV and perhaps delineate individuals at risk. The molecular basis for this approach, its limitations, and future prospects for immunodiagnosis are the subject of this review.

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Detection of human papillomavirus capsid antigens in various squamous epithelial lesions using antibodies directed against the L1 and L2 open reading frames

Cited by 54 publications

References 37 publications

Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.

Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.

Bovine Serological Response to a Recombinant BPV-1 Major Capsid Protein Vaccine

Pathobiology of papillomavirus-related cervical diseases: prospects for immunodiagnosis

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