Human papillomavirus type 16 E2 protein transactivation and repression functions
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Craigo J; Gray H; DeLucia A
Faseb Journal
1997
1997-07
Journal Article or Conference Abstract Publication
n/a
Inhibition of human papillomavirus type 16 gene expression by nordihydroguaiaretic acid plant lignan derivatives.
Antiviral Agents/*pharmacology; Cultured; Female; Gene Expression Regulation; Genetic/drug effects; HIV Long Terminal Repeat/drug effects; Humans; Lignans/chemistry/pharmacology; Masoprocol/*analogs & derivatives/*pharmacology; Papillomaviridae/*genetics; Promoter Regions; Simian virus 40/genetics; Tumor Cells; Viral/*drug effects
Several methylated derivatives of a plant lignan, nordihydroguaiaretic acid (NDGA) were found to be potent anti-viral agents by suppressing Sp1 regulated transcription within the sexually transmitted viruses human immunodeficiency virus (HIV) and herpes simplex virus (HSV). A prominent Sp1 DNA binding site within many human papillomavirus (HPV) promoters has been noted to play an active role in HPV gene expression. In this report it is shown that the three NDGA derivatives, Mal.4, M(4)N, and tetra-acetyl NDGA can also inhibit gene expression from the early promoter P(97) of HPV16. The drug activity on gene expression was measured after DNA transfection of recombinant vector constructs linking the viral promoter and enhancer elements to the luciferase reporter gene. Using the specific luciferase activity as the indicator of gene expression, Mal.4 and M(4)N were found to be active in a dose dependent manner that is in the same range of concentrations reported for the promoters of HIV, HSV, and simian virus 40 (SV40) while tetra-acetyl NDGA was much more active in suppression of the HPV P(97) promoter activity than Mal.4 and M(4)N. The drugs showed limited to no effect on gene expression driven by the adenovirus major late promoter and the cytomegalovirus (CMV) promoter. Hence, such drug derivatives may be significant in the therapy of papillomavirus infections and their associated induced human cancers.
Craigo J; Callahan M; Huang R C; DeLucia A L
Antiviral research
2000
2000-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0166-3542(00)00089-9" target="_blank" rel="noreferrer noopener">10.1016/s0166-3542(00)00089-9</a>
Uterine cervix adenocarcinoma with both human papillomavirus type 18 and tumor suppressor gene p53 mutation from a woman having an intact hymen.
*Genes; *Hymen; *Mutation; Adenocarcinoma/*genetics; Adult; DNA; Female; Gene Deletion; Genome; Humans; Neoplasm/genetics; p53; Papillomaviridae/classification/*genetics; Polymerase Chain Reaction; Polymorphism; Sexually Transmitted Diseases; Single-Stranded Conformational; Uterine Cervical Neoplasms/*genetics; Viral/genetics
Human papillomavirus (HPV) type 18 DNA was found in an aggressively invasive adenocarcinoma tumor from a woman who had an intact hymen and denied any prior sexual intercourse. The viral DNA was detected within the tumor tissue by polymerase chain reaction (PCR) using consensus primers for the L1 region of oncogenic high-risk genital HPVs. In order to determine mutations within the tumor suppressor gene p53, the gene exons were amplified by PCR followed by single-stranded conformation polymorphism (SSCP) analysis. The appearance of a mutation in exon 8 of the p53 gene suggested by SSCP was directly confirmed by DNA sequencing of the exon. The sequencing showed a single base deletion that may truncate the protein by introducing a early stop codon in the messenger RNA. This early truncation could be expected to affect the proper oligomerization of the p53 protein and hence its DNA-binding activity. The results show that genital oncogenic human papillomaviruses may be passed by nonsexual routes and suggest that the virus may work in concert with p53 mutations to help the infected tissue progress toward invasive cancer.
Craigo J; Hopkins M; DeLucia A
Gynecologic oncology
1995
1995-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/gyno.1995.9949" target="_blank" rel="noreferrer noopener">10.1006/gyno.1995.9949</a>