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A B Jenson

Publications and source records attributed to A B Jenson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Papillomavirus capsid binding and uptake by cells from different tissues and species.

The inability of papillomaviruses (PV) to replicate in tissue culture cells has hampered the study of the PV life cycle. We investigated virus-cell interactions by the following two methods: (i) using purified bovine PV virions or human PV type 11 (HPV type 11) virus-like particles (VLP) to test the binding to eukaryotic cells and (ii) using different VLP-reporter plasmid complexes of HPV6b, HPV11 L1 or HPV11 L1/L2, and HPV16 L1 or HPV16 L1/L2 to study uptake of particles into different cell lines. Our studies showed that PV capsids bind to a broad range of cells in culture in a dose-dependent manner. Binding of PV capsids to cells can be blocked by pretreating the cells with the protease trypsin. Penetration of PV into cells was monitored by using complexes in which the purified PV capsids were physically linked to DNA containing the gene for beta-galactosidase driven by the human cytomegalovirus promoter. Expression of beta-galactosidase occurred in < 1% of the cells, and the efficiency of PV receptor-mediated gene delivery was greatly enhanced (up to 10 to 20% positive cells) by the use of a replication-defective adenovirus which promotes endosomal lysis. The data generated by this approach further confirmed the results obtained from the binding assays, showing that PV enter a wide range of cells and that these cells have all functions required for the uptake of PV. Binding and uptake of PV particles can be blocked by PV-specific antisera, and different PV particles compete for particle uptake. Our results suggest that the PV receptor is a conserved cell surface molecule(s) used by different PV and that the tropism of infection by different PV is controlled by events downstream of the initial binding and uptake.

Animals↗
PubMed1995

Human papillomaviruses: their clinical significance in the management of cervical carcinoma.

Studies have shown a strong association between certain human papillomaviruses and the development of cervical carcinoma and its precursor lesions. The oncogenic potential of papillomaviruses has been clearly demonstrated in both laboratory animals and cultured cells. Recent advances in our understanding of viral pathogenesis have provided insights into the natural history of papillomavirus infection and subsequent development of neoplasia. A more thorough understanding of the molecular mechanisms responsible for viral oncogenesis will facilitate the development of novel preventive and therapeutic strategies to prevent and treat papillomavirus-associated cervical neoplasias. Strategies under current investigation are focusing on the induction of effective humoral and cell-mediated immunity, the expression of HPV gene products, and cofactors that interact with HPV gene products to affect cell transformation. As a result of these investigative efforts, prophylactic HPV capsid vaccines and other gene therapies may soon become clinically available.

Cell Transformation, Neoplastic↗
PubMed1994

Human papillomavirus types 6 and 11 have antigenically distinct strongly immunogenic conformationally dependent neutralizing epitopes.

Antibodies reactive to HPV types 6 and 11 were tested in ELISA and HPV-11 neutralization assays to determine whether these closely related types shared cross-reactive neutralizing epitopes. A series of HPV-11 neutralizing monoclonal antibodies (N-MAbs) that targeted conformational epitopes on infectious HPV-11 and HPV-11 L1 virus-like particles (VLPs) were tested for type-specificity of reactivity using intact HPV-6 L1 VLPs. Polyclonal antisera generated against intact HPV-6 L1 VLPs were also tested for HPV-11 neutralizing capacity using the athymic mouse xenograft system. The results demonstrated that conformationally dependent neutralizing epitopes on HPV-11 were very type-specific. Three of the four HPV-11 N-MAbs were negative for binding to HPV-6 L1 VLP, and the fourth demonstrated binding to HPV-6 L1 VLPs that was several orders of magnitude weaker than its binding to HPV-11 L1 VLP. The polyclonal anti-HPV-6 L1 VLP antiserum was only partially protective against HPV-11 infectivity even at a low dilution of 1:100. In contrast, polyclonal anti-HPV-11 L1 VLP antiserum was completely protective at dilutions greater than 1:10,000.

Animals↗
PubMed1994

Role of conformational epitopes expressed by human papillomavirus major capsid proteins in the serologic detection of infection and prophylactic vaccination.

Human papillomaviruses (HPVs) cause a variety of cutaneous warts, mucosal condylomata, and dysplasias and are etiologic in cervical cancer. Papillomavirus (PV) conformational epitopes on the surface of virions are type-specific and are the target of neutralizing antibodies. In this study, we describe two methods of in vitro expression of HPV major capsid (L1) proteins which mimicked conformational epitopes and demonstrate their type specificity and ability to react with neutralizing and/or conformation-dependent antibodies. The L1 open reading frames (ORFs) for HPV-1, 6, 11, and 16 were molecularly cloned into a SV 40 expression vector and the encoded gene products were expressed in mammalian (cos) cells. Similarly, the L1 ORFs for HPV-6, 11, 16, and 18 were molecularly cloned into recombinant baculovirus and the encoded gene products were expressed in insect (SF9) cells. The expressed L1 proteins reacted by immunofluorescence and immunoprecipitation with polyclonal and monoclonal antibodies generated against their corresponding native virions and by Western blotting with antibodies that recognized nonconformational epitopes of denatured virions. The recombinant L1 proteins expressed conformational epitopes in both cos and Sf9 cells that were type-specific and displayed neutralizing epitopes. The ability to express, purify, and qualitate the reactivity of recombinant L1 proteins will now permit the serologic analysis of host response to HPV infection and the development of prophylactic PV subunit vaccines.

Animals↗
PubMed1994

Canine oral papillomavirus genomic sequence: a unique 1.5-kb intervening sequence between the E2 and L2 open reading frames.

The canine oral papillomavirus (COPV) is associated with oropharyngeal papillomatosis in dogs, coyotes, and wolves. We have determined the complete nucleotide sequence of COPV, the largest of all known PV genomes (8607 bp). The genomic architecture of the COPV genome is similar to that of other PVs except for a unique and large noncoding region of 1.5 kb between the end of the early region (E2) and the beginning of the late region (L2) and a small (345 bp) upstream regulatory region between the end of L1 and the beginning of E6. Although COPV displays a primarily mucosal tropism, the COPV nucleotide sequence showed the highest overall similarity to cutaneous papillomaviruses such as HPV-1, HPV-63, CRPV (cottontail rabbit PV), FdPV (Felis domesticus PV), and MnPV (Mastomys natalensis PV).

Amino Acid Sequence↗
PubMed1994

Interaction of papillomaviruses with the cell surface.

To initiate an investigation of the initial step in papillomavirus infection, we have examined the interaction of bovine papillomavirus type 1 (BPV) virions with C127 cells by two assays, binding of radioiodinated BPV virions to cell monolayers and BPV-induced focal transformation. Under physiological conditions, the labeled virions bound to the cell surface in a dose-dependent manner within 1 h. Antibody studies indicated that the interaction was specific and related to infectivity: polyclonal sera raised to BPV virions or to baculovirus-expressed BPV L1 virus-like particles (VLPs) inhibited BPV binding and focal transformation, while sera to denatured BPV virions, to denatured BPV L1, or to human papillomavirus type 16 (HPV-16) VLPs were not inhibitory. An exception was that antisera to BPV L2 were neutralizing but did not inhibit binding. Unlabeled BPV virions and BPV VLPs competed with binding to the cell surface in a concentration-dependent manner. Binding to the cell surface appeared to depend primarily on L1, since BPV VLPs composed of L1 alone or of L1/L2 were equally effective in inhibiting binding and focal transformation. VLPs of HPV-16 also inhibited BPV binding and BPV transformation of C127 cells, suggesting that they interact with the same cell surface molecule(s) as BPV virions. Radiolabeled BPV bound specifically to several mammalian cell lines of fibroblastic and epithelial origin, as well as to a human schwannoma and melanoma lines, although some lines bound up to 10 times as many counts as others. Radiolabeled HPV-16 VLPs bound to both human keratinocytes and mouse C127 cells. The results suggest that papillomaviruses bind a widely expressed and evolutionarily conserved cell surface receptor.

Animals↗
PubMed1994

The expressed L1 proteins of HPV-1, HPV-6, and HPV-11 display type-specific epitopes with native conformation and reactivity with neutralizing and nonneutralizing antibodies.

Previous studies demonstrated that the human papillomavirus (HPV) type 1 L1 protein, expressed in cos cells by an SV40-based vector, displays conformational epitopes characteristic of native virions. In this study, we analyzed the expression of HPV-1, HPV-6, and HPV-11 L1 proteins in order to determine the forms of conformational epitopes expressed by recombinant L1 proteins. Using both immunofluorescence and immunoprecipitation techniques, polyclonal and monoclonal antibodies (MAbs) generated against native HPV-11 virions reacted with expressed L1 proteins of HPV-6 and/or HPV-11, but not HPV-1. Similarly, polyclonal antibodies and MAbs generated against HPV-1 virions reacted with the expressed L1 protein of HPV-1, but not HPV-6 or HPV-11. Of two MAbs that neutralized HPV-11 infection of murine fetal foreskin xenografts, one reacted with the expressed L1 protein of both HPV-6 and HPV-11, and the other reacted with HPV-11 only. A nonneutralizing conformationally dependent MAb reacted with the expressed L1 protein of both HPV-6 and HPV-11. These results demonstrate that expressed HPV L1 proteins retain type-specific, neutralizing, and nonneutralizing conformational epitopes and that cos cells may be utilized to evaluate host immune responses to such epitopes.

Animals↗
PubMed1994

A formalin-inactivated vaccine protects against mucosal papillomavirus infection: a canine model.

A formalin-inactivated canine oral papilloma homogenate was used as a vaccine to prevent infection by the oncogenic, mucosotropic canine oral papillomavirus (COPV) in beagle dogs. Twenty-six dogs received 2 doses of phosphate-buffered saline intradermally and 99 dogs received 2 doses of the inactivated vaccine. One month after the second dose all dogs were challenged with infectious COPV by scarification of the oral mucosa. All of the control dogs developed papillomas by 6-8 weeks after challenge while none of the vaccinated dogs did. This vaccine has been used successfully in approximately 60,000 line bred beagles with no untoward effects and with long-lasting protection. These data demonstrate that a systemically administered, formalin-inactivated vaccine can protect against mucosal infection by COPV and suggest approaches for the development of human papillomavirus vaccines.

Animals↗
PubMed1994

Involvement of canine oral papillomavirus in generalized oral and cutaneous verrucosis in a Chinese Shar Pei dog.

Severe papillomatosis developed in the oral cavity and spread throughout the haired skin of the trunk and limbs of an 8-month-old female Chinese Shar Pei dog. The dog had received corticosteroids prior to referral, which was associated with the onset of demodecosis and papillomatosis. Papillomavirus structural antigens were detected in biopsies by immunohistochemistry using a panel of monoclonal and polyclonal antibodies. An 8.2-kilobase papillomavirus-specific DNA molecule was detected in the cutaneous lesions by high stringency Southern blot hybridization using a cloned canine oral papillomavirus DNA probe. Restriction enzyme analysis revealed that the virus in the cutaneous lesions was identical to the canine oral papillomavirus. Discontinuation of the steroids combined with the use of a mitocide, antibiotics, and an autogenous vaccine resolved the demodecosis and papillomatosis. This case report suggests that corticosteroid-induced immunosuppression can expand the tissue tropism of papillomaviruses.

Adrenal Cortex Hormones↗
PubMed1993

Major histocompatibility complex and human papillomavirus type 16 E7 expression in high-grade vulvar lesions.

To determine whether expression of the human papillomavirus (HPV) type 16 E7 open reading frame influences expression of major histocompatibility complex (MHC) antigens on the surface of squamous epithelial cells, serial frozen sections from seven HPV type 16-positive, high-grade vulvar intraepithelial neoplasia (VIN 2-3) lesions were tested for viral transcription by RNA-RNA in situ hybridization, for MHC expression by immunohistochemical staining with antibodies to MHC class I and II molecules, and for keratinocyte differentiation by immunohistochemical staining with anti-filaggrin and cytokeratin 10 antibodies. Despite the histologic appearance of high-grade VIN lesions, expression patterns of cytokeratin 10 and filaggrin suggested a certain degree of keratinocyte differentiation in all specimens. These differentiation markers were especially prominent in parakeratotic and hyperkeratotic superficial areas, which did not express MHC antigens or contain E7 mRNA. Expression of MHC class I molecules within dysplastic tissues was greater than within HPV type 16-negative, normal vulvar epithelium from the same patients. In five of the VIN 2-3 specimens anti-MHC class I antibodies reacted more strongly with cells of the basal and suprabasal layers than with cells of the epithelial surface. In one lesion basal cells stained less intensively than surface cells, whereas in another specimen all epithelial layers were equally MHC class I positive. Staining with anti-MHC class II antibodies was generally restricted to isolated foci, representing invading lymphocytes, tissue macrophages, and Langerhans cells. In two lesions, however, there was heterogeneous keratinocyte expression of MHC class II proteins, perhaps due to inflammation. Major histocompatibility complex antigen detection was independent of the presence or distribution pattern of E7-specific transcripts. Hence, a correlation between MHC and E7 expression appears unlikely in warty VIN lesions.

Adult↗
PubMed1993

Pathogenesis of adenovirus type 5 pneumonia in cotton rats (Sigmodon hispidus).

Cotton rats (Sigmodon hispidus) were inoculated intranasally with 10(2.0) to 10(10.0) PFU of human adenovirus type 5. The virus replicated to a high titer in pulmonary tissues, with the peak titer being proportional to the input dose. The 50% lethal dose was 10(9.4) PFU. Histopathologic changes were proportional to the infecting inoculum and included the infiltration of interstitial and intra-alveolar areas, moderate damage to bronchiolar epithelium, and cellular infiltration of peribronchiolar and perivascular regions. These changes could be divided into two phases: an early phase (affecting alveoli, bronchiolar epithelium, and peribronchiolar regions) with an infiltrate consisting primarily of monocytes-macrophages and neutrophils, with occasional lymphocytes, and a later phase (affecting peribronchiolar and perivascular regions) with an infiltrate consisting almost exclusively of lymphocytes. In both phases, the predominant process was the response of the host to infection, rather than direct viral damage to infected cells. An infecting inoculum of 10(8.0) PFU or larger caused severe damage to type II alveolar cells, which were swollen, showed a loss of lamellar bodies, and were surrounded by polymorphonuclear leukocytes and macrophages. No evidence of complete viral replication was found in type II alveolar cells.

Adenoviridae Infections↗
PubMed1993

Identification of conformational epitopes of the BPV-1 capsid recognized by competitive inhibition of sera from infected or immunized animals.

Conformational papillomavirus (PV) capsid epitopes are the major targets of neutralizing antibodies. BPV1 virion surface epitopes were analyzed for type-specificity, induction of neutralization, and topographical location with antibodies from selected humans, and BPV1 or -2 immunized or infected cattle, rabbits and mice. Rabbit sera produced against deer PV (DPV) or BPV2 and human sera reacted with intact BPV1 in ELISA, indicating the presence of cross-reactive conformational epitopes on the surface of BPV1 virions. However, competitive binding assays performed on intact BPV1 capsids using unlabeled and biotin-conjugated antibodies revealed that the conformational epitopes of BPV1 recognized by rabbit, bovine and human antibodies were topographically different. Only hyperimmune sera to intact BPV1, BPV2 or DPV neutralized BPV1-induced focus formation of C127 cells with the highest neutralizing titers observed for bovine and rabbit antibodies produced against intact BPV1. Our study showed the complexity of conformational capsid epitopes of BPV1 and their importance for inducing a protective humoral immune response in animals inoculated or immunized with BPV1.

Antibodies, Viral↗
PubMed1993

Pathogenesis of Pichinde virus infection in strain 13 guinea pigs: an immunocytochemical, virologic, and clinical chemistry study.

Pichinde virus has been adapted to produce lethal infection of Strain 13 guinea pigs. Viral replication and presence of viral antigen in frozen tissues stained by immunofluorescence has been previously described. Further investigation into the pathogenesis of this disease has been hampered by the lack of a light microscopic method for correlating histologic lesions and the presence of Pichinde viral antigens. For this purpose, we developed a sensitive immunocytochemical technique for staining Pichinde viral antigens in formalin-fixed, paraffin-embedded tissue. Enhancement of the immunocytochemical staining with nickel chloride markedly improved detection of viral antigens. We examined frozen and formalin-fixed tissues from Strain 13 guinea pigs for viral antigens by light microscopy and immunocytochemistry at various intervals after infection with Pichinde virus. Progressive involvement of different tissues correlated with organ injury measured by serum biochemical abnormalities. Pichinde viral antigen was first detected in splenic macrophages five days after infection and their subsequent destruction facilitated persistent viremia. The inability to clear virus led to multiple organ infection and vascular involvement. Ensuing infections involved particularly the liver, spleen, adrenal glands, lungs, and intestines. Gastroenteritis developed, with extensive involvement of the muscularis mucosa throughout the gastrointestinal tract. Water and food intake decreased rapidly after day 8, leading to marked weight loss. Fatty changes of the liver suggested metabolic derangement that was further exacerbated terminally by adrenal infection and pulmonary impairment.

Adrenal Glands↗
PubMed1992

HPV-1 L1 protein expressed in cos cells displays conformational epitopes found on intact virions.

Seven polyclonal and monoclonal antibodies were characterized for their ability to react specifically with either conformational or nonconformational epitopes of the HPV-1 virion. Using these antibodies, it was shown that the HPV-1 L1 protein (when expressed by an SV40 vector in cos cells) displayed conformational epitopes characteristic of intact viral particles. In addition, the L1 capsid protein was translocated normally into cell nuclei, was of appropriate size (57 kDa), and could be isolated in native form by immunoprecipitation techniques. Most importantly, the screening of expressed papillomavirus capsid proteins for reactivity with conformation-dependent antibodies represents a new, general methodology for ensuring that such proteins will be suitable for use in vaccine development or in the serologic detection/typing of human papillomavirus infections.

Animals↗
PubMed1992

Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types.

During the years 1982-1989, 2627 women were recruited into eight studies analyzing the relationship between human papillomavirus (HPV) infection and cervical neoplasia. Subsequently, each individual was assigned as either a case or control, and each cervical sample was rescreened for HPV DNA by low-stringency Southern blot hybridization. Positive samples were retested at high stringency with specific probes for HPVs 6/11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and (in most instances) 58. Most cases (153 cancers, 261 high-grade and 377 low-grade squamous intraepithelial lesions) had target or cone biopsies; all 270 borderline atypia subjects and more than 85% of the 1566 normal controls had cytology plus colposcopy/cytology. Scientists performing HPV testing were masked to the clinical diagnoses. Human papillomavirus DNA was detected in 79.3% of specimens from women with definite cervical disease (627 of 791), in 23.7% of borderline atypia subjects (64 of 270), and in 6.4% of normal subjects (101 of 1566). Graphic analysis of odds ratios at each point in the diagnostic spectrum defined four categories: 1) "low risk" (HPVs 6/11, 42, 43, and 44), present in 20.2% (76 of 377) of low-grade lesions but absent in all 153 cancers; 2) "intermediate risk" (HPVs 31, 33, 35, 51, 52, and 58), detected in 23.8% (62 of 261) of high-grade squamous intraepithelial lesions but only 10.5% (16 of 153) of cancers; 3) "high risk/HPV 16," associated with 47.1% of both high-grade intraepithelial lesions (123 of 261) and cancers (72 of 153); and 4) "high risk/HPV 18" (HPVs 18, 45, and 56), found in 26.8% (41 of 153) of invasive carcinomas but only 6.5% (17 of 261) of high-grade intraepithelial lesions. The presence of an oncogenic HPV type conferred relative risks ranging at 65.1-235.7 for the occurrence of a high-grade lesion and 31.1-296.1 for an invasive cancer.

Blotting, Southern↗
PubMed1991

Comparison of neutralization of BPV-1 infection of C127 cells and bovine fetal skin xenografts.

BPV-1 induces focus formation in murine C127 cells and fibropapillomas in bovine fetal skin xenografts. In this study, we compared the specificity of neutralization of BPV-1 in both assay systems, using sera and monoclonal antibodies (MAbs) selected to define neutralizing epitopes. Sera from rabbits and cattle, inoculated with intact BPV-1 or PBV-2 virions, neutralize BPV-1 infectivity in both C127 cells and xenografts. Selected human sera and murine MAbs that react with intact BPV-1 particles, serum of a rabbit immunized with denatured BPV-1 particles, and sera from calves vaccinated with a recombinant LI fusion protein did not neutralize BPV-1 infection in either system. It was concluded that neutralization of BPV-1 infection of C127 cells and bovine fetal skin xenografts by hyperimmune sera is specific and concordant for both assay systems, and involves conformational BPV-1 capsid epitopes.

Animals↗
PubMed1991

Should cervical cytologic testing be augmented by cervicography or human papillomavirus deoxyribonucleic acid detection?

Criticism of the Papanicolaou smear in the lay press and recent federal legislation regulating cytology laboratories indicate a need to reappraise cervical cancer screening programs. This study directly compares three potential screening tests, used alone or in combination. A total of 1012 women aged 18 to 35 years were screened by cytologic testing, cervicography, and hybridization for human papillomavirus deoxyribonucleic acid, with discrepancies being referred by the last two authors. After findings from the entire lower genital tract were combined, 116 women (11.5%) showed definite clinical abnormalities (either exophytic vulvovaginal condylomas or cervical squamous intraepithelial lesions). Another 72 (7.2%) had positive Southern blot hybridizations without accompanying viral expression, yielding a cumulative frequency for established disease or latent infection of 18.6%. When associated vulvovaginal condylomas are disregarded, final groupings with regard to cervical pathologic classification were: 23 high-grade and 71 low-grade squamous intraepithelial lesions, 164 cases of equivocal atypia (34 of which had detectable human papillomavirus deoxyribonucleic acid), and 754 cases with negative results (38 of which had detectable human papillomavirus deoxyribonucleic acid). Cervical screening tests were compared principally by plotting increasingly liberal recall criteria onto receiver operating characteristic curves (i.e., graphs of true-positive results on the Y axis versus false-positive results on the X axis). Used individually, each screening test was valid, but none was substantially better than the others. No matter how liberal the recall criteria, no single test was able to detect all of the 23 definite precursors in this sample. Applying conventional recall criteria (i.e., high- or low-grade lesion suspected), cytologic testing alone detected 12 high-grade squamous intraepithelial lesions (52.2%), at a cost of having to perform colposcopy in 8.7% of the sample. Combining all three tests and setting the end point as just a high-positive result by at least one test, 19 high-grade squamous intraepithelial lesions (83%) were detected, with a recall of 7%. Optimal test performance (96% sensitivity, 4% recall) would have been attained by recalling all patients with high-grade cytologic results or positive cervicography results, plus any patients with low-grade morphologic atypia in which hybridization detected an oncogenic human papillomavirus type. Our conclusions are as follows: (1) Cytologic detection rates are markedly improved by a second or third test; (2) increased screening costs could be offset by not recalling patients with minor lesions with no apparent potential for progression.

Adolescent↗