scholarly journals Cervical lesions are associated with human papillomavirus type 16 intratypic variants that have high transcriptional activity and increased usage of common mammalian codons

2000 ◽  
Vol 81 (6) ◽  
pp. 1517-1527 ◽  
Author(s):  
Jon M. Bible ◽  
William G. Starkey ◽  
Christine Mant ◽  
Jennifer M. Best ◽  
Jangu E. Banatvala ◽  
...  
2010 ◽  
Vol 84 (16) ◽  
pp. 8219-8230 ◽  
Author(s):  
Monika Somberg ◽  
Stefan Schwartz

ABSTRACT Our results presented here demonstrate that the most abundant human papillomavirus type 16 (HPV-16) mRNAs expressing the viral oncogenes E6 and E7 are regulated by cellular ASF/SF2, itself defined as a proto-oncogene and overexpressed in cervical cancer cells. We show that the most frequently used 3′-splice site on the HPV-16 genome, site SA3358, which is used to produce primarily E4, E6, and E7 mRNAs, is regulated by ASF/SF2. Splice site SA3358 is immediately followed by 15 potential binding sites for the splicing factor ASF/SF2. Recombinant ASF/SF2 binds to the cluster of ASF/SF2 sites. Mutational inactivation of all 15 sites abolished splicing to SA3358 and redirected splicing to the downstream-located, late 3′-splice site SA5639. Overexpression of a mutant ASF/SF2 protein that lacks the RS domain, also totally inhibited the usage of SA3358 and redirected splicing to the late 3′-splice site SA5639. The 15 ASF/SF2 binding sites could be replaced by an ASF/SF2-dependent, HIV-1-derived splicing enhancer named GAR. This enhancer was also inhibited by the mutant ASF/SF2 protein that lacks the RS domain. Finally, silencer RNA (siRNA)-mediated knockdown of ASF/SF2 caused a reduction in spliced HPV-16 mRNA levels. Taken together, our results demonstrate that the major HPV-16 3′-splice site SA3358 is dependent on ASF/SF2. SA3358 is used by the most abundantly expressed HPV-16 mRNAs, including those encoding E6 and E7. High levels of ASF/SF2 may therefore be a requirement for progression to cervical cancer. This is supported by our earlier findings that ASF/SF2 is overexpressed in high-grade cervical lesions and cervical cancer.


PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0129452 ◽  
Author(s):  
Nina Milutin Gašperov ◽  
Ivan Sabol ◽  
Pavao Planinić ◽  
Goran Grubišić ◽  
Ivan Fistonić ◽  
...  

2007 ◽  
Vol 17 (1) ◽  
pp. 107-117 ◽  
Author(s):  
P. Laikangbam ◽  
S. Sengupta ◽  
P. Bhattacharya ◽  
C. Duttagupta ◽  
Th. Dhabali Singh ◽  
...  

Human papillomavirus (HPV) DNA in cervical scrape samples of married women from Manipur (n= 692) and Sikkim (n= 415) in northeast India was determined and compared with that of women from West Bengal (n= 1112) in eastern India by polymerase chain reaction. HPV prevalence was lower in Manipur (7.4%) than in Sikkim (12.5%), which was closely followed by West Bengal (12.9%). HPV18 was predominant in Manipur (2.03%) and strikingly lower (0.2%) in Sikkim and West Bengal (0.9%), while the reverse was true for HPV16. The proportion of HPV16/18 infections in Manipur (3.3%, 22/672) and Sikkim (3.89%, 14/359) were comparable and significantly lower compared to that in West Bengal (7.8%, 79/1007) among women having normal cervical cytology. Such prevalence was similar among all age groups in Manipur: increased with age for women in Sikkim and dropped with age for those in West Bengal similar to that reported previously. At age ≤30 years, HPV16/18 prevalence in Manipur (3.3%) and Sikkim (2.5%) was comparable but was significantly lower (P < 0.05) in contrast to that in West Bengal (8.8%). Among abnormal cytologic lesions, HPV16/18 infections were significantly higher than in normals (P= 0.000) both in Sikkim (14.3%) and West Bengal (20.9%) and absent in Manipur. Such prevalence was noted among women in Sikkim aged >30 years and equally among those in West Bengal aged ≤30 or >30 years. Thus, women from northeast India, particularly from Manipur, appear less susceptible to HPV16/18 infection and related cervical lesions compared to those from West Bengal, where such proneness was prominently evident at age ≤30 years.


2000 ◽  
Vol 181 (4) ◽  
pp. 1234-1239 ◽  
Author(s):  
Michael E. Hagensee ◽  
Laura A. Koutsky ◽  
Shu‐Kuang Lee ◽  
Thomas Grubert ◽  
Jane Kuypers ◽  
...  

2014 ◽  
Vol 136 (6) ◽  
pp. E638-E645 ◽  
Author(s):  
Karolina Louvanto ◽  
Eduardo L. Franco ◽  
Agnihotram V. Ramanakumar ◽  
Nataša Vasiljević ◽  
Dorota Scibior-Bentkowska ◽  
...  

2009 ◽  
Vol 81 (9) ◽  
pp. 1627-1634 ◽  
Author(s):  
Valeria Cento ◽  
Massimo Ciccozzi ◽  
Luigi Ronga ◽  
Carlo Federico Perno ◽  
Marco Ciotti

Author(s):  
Katarzyna Sitarz ◽  
Jolanta Kopec ◽  
Barbara Zawilinska ◽  
Malgorzata Klimek ◽  
Slawa Szostek

The E1 and E2 genes of the human papillomavirus encode the so-called early proteins, their sequences are conserved, and regulatory functions are associated with the viral oncoproteins. The purpose of this study is to determine the HPV16 E1 and E2 mutations appearing in the female population of southern Poland, depending on the severity of cervical pathological changes. We also take into account the number of E1 and E2 mutations detected in the E6 gene variant (350G or 350T). This publication is one of the first in the Central and Eastern Europe to deal with this topic. We identified 4 mutations in the E1 gene and 24 mutations in the E2 gene that have not been described so far. In three cases of squamous cell carcinoma a C3409T mutation occurred, which is widely described as oncogenic. This mutation lies in the 3243-3539 area of the E2 hinge region. Statistical analyses show a possible relationship of mutations in this area with oncogenesis. The discovered dependencies may be important in the context of oncogenesis, however, a study with a larger group of patients is needed in order to confirm this view.


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