ABSTRACT
Scarce data are available on the expression of papillomavirus genome and the frequency of alternatively spliced E6E7 mRNAs in invasive cervical cancer. We carried out a comprehensive characterization of HPV expression by RNA-Seq analysis in 22 invasive cervical cancer with HPV16 or HPV18, characterizing the presence of integrated/episomal viral DNA, the integration sites in human genome and the proportion of alternative splicing products of E6 and E7 genes. The expression patterns suggested the presence of episomal and/or integrated viral DNA, with integration detected in most tumors, frequently occurring within human genes in HPV18+ and in intergenic regions in HPV16+ tumors. Alternative splicing of E6E7 transcripts showed E6*I as the most frequent isoform for both viral types, followed by E6*II and E6/E7 (unspliced) transcripts in HPV16+, and by E6/E7 in HPV18+ tumors. Previously described E6*VI and E6*V transcript isoforms for HPV16, and E6*X for HPV18, were rare or not detected.
Subject(s)
DNA-Binding Proteins , Gene Expression Regulation, Neoplastic , Gene Expression Regulation, Viral , Human papillomavirus 16 , Human papillomavirus 18 , Oncogene Proteins, Viral , Papillomavirus E7 Proteins , RNA-Seq , Repressor Proteins , Uterine Cervical Neoplasms , Virus Integration , Alternative Splicing , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Female , Human papillomavirus 16/genetics , Human papillomavirus 16/metabolism , Human papillomavirus 18/genetics , Human papillomavirus 18/metabolism , Humans , Oncogene Proteins, Viral/biosynthesis , Oncogene Proteins, Viral/genetics , Papillomavirus E7 Proteins/biosynthesis , Papillomavirus E7 Proteins/genetics , Repressor Proteins/biosynthesis , Repressor Proteins/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virologyABSTRACT
To evaluate the impact of HPV immunization and possible changes in virus type-specific prevalence associated with cervical cancer, it is important to obtain baseline information based on socioeconomic, educational, and environmental characteristics in human populations. We describe these characteristics and the type-specific HPV distribution in 1,183 women diagnosed with cervical cancer in two Brazilian healthcare institutions located at the Southeastern (Rio de Janeiro/RJ) and the Amazonian (Belém/PA) regions. Large differences were observed between women in these regions regarding economic, educational, and reproductive characteristics. The eight most frequent HPV types found in tumor samples were the following: 16, 18, 31, 33, 35, 45, 52, and 58. Some HPV types classified as unknown or low risk were found in tumor samples with single infections, HPV 83 in RJ and HPV 11, 61, and 69 in PA. The proportion of squamous cervical cancer was lower in RJ than in PA (76.3% versus 87.3%, p < 0.001). Adenocarcinoma was more frequent in RJ than in PA (13.5% versus 6.9%, p < 0.001). The frequency of HPV 16 in PA was higher in younger women (p < 0.05). The success of a cervical cancer control program should consider HPV types, local health system organization, and sociodemographic diversity of Brazilian regions.
Subject(s)
Papillomaviridae/genetics , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Adolescent , Adult , Aged , Brazil/epidemiology , Female , Genotype , Humans , Immunization Programs/statistics & numerical data , Middle Aged , Papillomavirus Infections/epidemiology , Prevalence , Reference Values , Socioeconomic Factors , Uterine Cervical Neoplasms/epidemiology , Young AdultABSTRACT
BACKGROUND: The allergenicity of Ricinus communis L. (castor bean, Euphorbiaceae) is associated with components of its seeds and pollen. Castor bean allergy has been described not only in laboratory workers, but also in personnel working in oil processing mills, fertilizer retail, the upholstery industry and other industrial fields. In the present study, we describe the critical amino acids in the IgE-binding epitopes in Ric c 1 and Ric c 3, two major allergens of R. communis. In addition, we also investigate the cross-reactivity between castor bean and some air and food allergen extracts commonly used in allergy diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: The IgE reactivity of human sera from atopic patients was screened by immune-dot blot against castor bean allergens. Allergenic activity was evaluated in vitro using a rat mast cell activation assay and by ELISA. Cross-reactivity was observed between castor bean allergens and extracts from shrimp, fish, gluten, wheat, soybean, peanut, corn, house dust, tobacco and airborne fungal allergens. We observed that treatment of rat and human sera (from atopic patients) with glutamic acid reduced the IgE-epitope interaction. CONCLUSIONS/SIGNIFICANCE: The identification of glutamic acid residues with critical roles in IgE-binding to Ric c 3 and Ric c 1 support the potential use of free amino acids in allergy treatment.
