scholarly journals Decreased Migration of Langerhans Precursor-Like Cells in Response to Human Keratinocytes Expressing Human Papillomavirus Type 16 E6/E7 Is Related to Reduced Macrophage Inflammatory Protein-3α Production

2005 ◽  
Vol 79 (23) ◽  
pp. 14852-14862 ◽  
Author(s):  
Jennifer C. Guess ◽  
Dennis J. McCance

ABSTRACT Infection with high-risk human papillomavirus (HPV) types, particularly types 16 and 18, contributes to 90% of cervical cancer cases. HPV infects cutaneous or mucosal epithelium, tissue that is monitored for microbial infection or damage by Langerhans cells. In lesions produced by HPV type 16, there is a reduction in numbers of immune cells, especially Langerhans cells. Langerhans precursor cells selectively express CCR6, the receptor for macrophage inflammatory protein 3α (MIP-3α), and function as potent immune responders to inflamed epithelium and initiators of the innate immune response. It has been reported that E6 and E7 of high-risk HPVs interfere with immune mediators in order to suppress the recruitment of immune cells and antiviral activities of infected cells. Here we show that, following proinflammatory stimulus, HPV-16 E6 and E7 inhibit MIP-3α transcription, resulting in suppression of the migration of immature Langerhans precursor-like cells. Interestingly, the E6 and E7 proteins from the low-risk HPV types also inhibited MIP-3α transcription. These results suggest that one mechanism by which HPV-infected cells suppress the immune response may be through the inhibition of a vital alert signal, thus contributing to the persistence of HPV infection.

1970 ◽  
Vol 25 (1) ◽  
pp. 65-68 ◽  
Author(s):  
Tahmina Sultana ◽  
Mohsina Huq ◽  
Anadil Alam ◽  
Dipak Kumar Mitra ◽  
Donald James Gomes

In developing countries, cervical cancer is the most common cause of cancer related to mortality in women. But the epidemiology of human papillomavirus (HPV) in different areas of Bangladesh is largely unknown both in risk groups and in the general population. The objective of the present study was to determine the risk factors associated with having HPV and the prevalence of high-risk HPV types among women with highrisk behaviour and to assess its potential impact on preventive strategies as the sex workers are at increased risk for sexually transmitted infections (STI), HPV and hence cervical cancer. Cervical swab from 293 sex workers in Dhaka City between August and September 2003 and between February 2005 and May 2006 were screened for HPV DNA using an HPV short fragment (E6) polymerase chain reaction (PCR) based assay. HPV positive samples were genotyped with nested multiplex polymerase chain reaction (NMPCR) for the highrisk types. The overall HPV prevalence in sex workers was 75.8%, whereas for the high risk type it was 49.8%. Prevalence of single genotype and multiple types of HPV was 33.1 and 16.7% respectively. The most prevalent high-risk HPV types, in order of prevalence rate, were HPV16, HPV18, HPV58, HPV45, HPV31 and HPV33. Both HPV 16 and HPV 18 were present in 21% of the cases. Targeting HPV 16 and 18 with prophylactic vaccines could possibly have an important impact on the incidence of invasive cervical carcinoma in this group of women. Primary prevention and cervical cancer screening programmes should be optimized more and run yearly among the general population. It is proposed to screen sex workers when they enter prostitution regardless of their age. Keywords: Human papillomavirus (HPV); High-risk HPV types; Cervical cancer; Sex workersDOI: http://dx.doi.org/10.3329/bjm.v25i1.4861 Bangladesh J Microbiol, Volume 25, Number 1, June 2008, pp 65-68


2021 ◽  
Vol 15 (09) ◽  
pp. 1339-1345
Author(s):  
Richard Tagne Simo ◽  
Arsène G Djoko Nono ◽  
Hervet Paulin Fogang Dongmo ◽  
Paul F Seke Etet ◽  
Bertrand Kiafon Fonyuy ◽  
...  

Introduction: Various Human papillomavirus (HPV) types cause cervical cancer, and represent the primary cause of cancer death in Africa and the second cause of most common cancers in Cameroon. Herein, we determined the prevalence of high-risk HPV types in women and associated cervical cytologic abnormalities in Yaounde, Cameroon. Methodology: A cross-sectional study targeting HPV-positive women aged 20 and over was conducted between March and June 2020 at the Saint Martin de Porres’ Health Centre in Yaounde. HPV tests were performed by PCR for detection of HPVs 16, 18, 33, and 45. The test was performed on 616 women using exfoliated cell specimens; then, we processed on cytological diagnosis with Pap smears on HPV positive specimens. Results: The HPV types tested were detected in 137 participants, of which 38.7% with multiple HPV infections, and the remaining part with single HPV infections of type HPV 16 (28.5%), HPV 18 (17.5%), HPV 33 (10.2%), and HPV 45 (5.1%). Cervical cytologic abnormalities were found in 69.34% of participants including: LSIL (49.63%), HSIL (15.32%), ASC-US (3.66%) and AGC (0.73%). Co-infections with HPV 16 and HPV 18 were significantly associated with HSIL (p = 0.001) lesions, while HPV 45 was more common in participants with normal cytology (p = 0.001). Cervical lesion occurrence was significantly associated with the number of sexual partners (p = 0.02) and history of oral contraceptive pill use (p = 0.001). Conclusions: Our results suggest that HPV 16 and 18 are predominant in Yaounde, and are associated with more severe precancerous lesions.


2006 ◽  
Vol 24 (36) ◽  
pp. 5630-5636 ◽  
Author(s):  
Lisa Licitra ◽  
Federica Perrone ◽  
Paolo Bossi ◽  
Simona Suardi ◽  
Luigi Mariani ◽  
...  

Purpose Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear. Patients and Methods To clarify how the presence of high-risk (HR) -HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery. Results Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and p16 expression were not prognostic by themselves. Conclusion Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.


2007 ◽  
Vol 119 (2) ◽  
pp. 457-463 ◽  
Author(s):  
Byung Eui Kim ◽  
Donald Y.M. Leung ◽  
Joanne E. Streib ◽  
Mark Boguniewicz ◽  
Qutayba A. Hamid ◽  
...  

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 690
Author(s):  
Ming-Kai Jhan ◽  
Ting-Jing Shen ◽  
Po-Chun Tseng ◽  
Yung-Ting Wang ◽  
Chiou-Feng Lin

The infection by dengue virus (DENV) of microglia causes cell activation and migration via a mechanism involving viral entry, RNA release, and Toll-like receptor 3 signaling. In this study, we demonstrated that secreted chemotactic factors present in microglial conditioned medium (MCM) facilitated cell motility in the murine BV2 microglial cells. The pharmacological disruption of lipid rafts/caveolae reduced DENV- and ultraviolet (UV)-inactivated MCM-induced microglial cell migration. An antibody-based cytokine/chemokine array showed an increase in macrophage inflammatory protein (MIP)-3β in MCM produced using DENV-infected cells. The pharmacological inhibition of c-Jun N-terminal kinase (JNK) retarded UV-MCM-induced microglial cell migration. These results demonstrate that secreted MIP-3β and its effect on the JNK signaling pathways mediates DENV-induced BV2 microglial cell migration.


2015 ◽  
Vol 53 (10) ◽  
pp. 3272-3279 ◽  
Author(s):  
K. Cuschieri ◽  
D. T. Geraets ◽  
C. Moore ◽  
W. Quint ◽  
E. Duvall ◽  
...  

As the demand for human papillomavirus (HPV)-related cervical screening increases, emerging HPV tests must be evaluated robustly using well-annotated samples, such as those generated in the Validation of HPV Genotyping Tests (VALGENT) framework. Through VALGENT, we assessed the performance of the BD Onclarity HPV assay, which detects 14 high-risk (HR) types and resolves six individual types and three groups of types. Consecutive samples from a screening population (n= 1,000), enriched with cytologically abnormal samples (n= 300), that had been tested previously with the GP5+/6+ PCR enzyme immunoassay (EIA) and the GP5+/6+ PCR LMNX assay (Diassay) were tested with the Onclarity assay. Type-specific HPV prevalences were analyzed according to age and cytological result. The accuracy of the Onclarity assay for the detection of cervical intraepithelial neoplasia grade 2+ (CIN2+) and CIN3+ was assessed relative to the GP5+/6+ EIA results by using noninferiority criteria. Overall agreement and type-specific agreement between the Onclarity assay and the GP5+/6+ LMNX assay were assessed. The prevalence of HPV types 16, 18, 31, and 45 increased with the severity of cytological results (Pfor trend, <0.05). For the detection of CIN2+, the Onclarity assay had a relative sensitivity of 1.02 (95% confidence interval [CI], 0.99 to 1.05;P< 0.001 for noninferiority) and a relative specificity of 0.99 (95% CI, 0.97 to 1.00;P= 0.186 for noninferiority). The kappa for agreement between the Onclarity assay and the GP5+/6+ LMNX assay for HR-HPV was 0.92 (95% CI, 0.89 to 0.94), and values for the six individual types ranged from 0.78 (95% CI, 0.68 to 0.87) for HPV-52 to 0.96 (95% CI, 0.93 to 0.99) for HPV-16. These data suggest that the Onclarity assay offers applications for clinical workstreams while providing genotyping information that may be useful for risk stratification beyond types 16 and 18.


1999 ◽  
Vol 8 (3) ◽  
pp. 173-175 ◽  
Author(s):  
S. Sakai ◽  
H. Kawamata ◽  
T. Kogure ◽  
N. Mantani ◽  
K. Terasawa ◽  
...  

We investigated the effect of ferulic acid (FA) and isoferulic acid (IFA), which are the main active components of the rhizoma ofCimicifuga heracleifolia(CH), an anti-inflammatory drug used frequently in Japanese traditional medicine, on the production of macrophage inflammatory protein-2 (MIR-2) in a murine macrophage cell line, RAW264.7, in response to respiratory syncytial virus (RSV) infection. Following the exposure of cells to RSV for 20 h, the MIP-2 level in condition medium was increased to about 20 ng/ml, although this level in mock-infected cells was negligible. In the presence of either FA or IFA, RSV-infected cells reduced MIP-2 production in a dose-dependent manner. These data suggest that FA and IFA might be responsible, at least in part, for the anti-inflammatory drug effect of CH extract through the inhibition of MIP-2 production.


2013 ◽  
Vol 23 (3) ◽  
pp. 527-532 ◽  
Author(s):  
Nora Berois ◽  
Patricia De Cremoux ◽  
Daniel Mazal ◽  
Adela Sica ◽  
Mabel Cedeira ◽  
...  

ObjectivesPersistent infection with specific genotypes of human papillomaviruses (HPVs) is the main cause of invasive cervical cancer (ICC). Only a few of the various HPV types account for most of the cases worldwide, and geographical differences in their distribution are evident. Data from locally prevalent genotypes are essential in view of introduction of HPV type-specific prophylactic vaccines.MethodsIn this work, we have investigated HPV type distribution in samples of ICC cases that occurred in Uruguayan women. DNA extracted from ICC treated in Centro Hospitalario Pereira Rossell of Montevideo between 1999 and 2007 were analyzed. Search and typing were performed by polymerase chain reaction using generic GP5+/GP6+ primers and specific primers for HPV types 16, 18, 33, and 45. Positive GP5+/GP6+ samples, which were negative for all 4 high-risk HPV-specific types screened were further analyzed by sequencing.ResultsHuman papillomavirus DNA sequences were found in 163 (92.6%) of 176 cases. The most prevalent genotypes were HPV16 (67.6%) and HPV18 (8.5%) followed by HPV45 (6.8%) and HPV33 (3.4%), as single or mixed infection. Other less frequent genotypes were HPV31, HPV35, HPV39, HPV51, HPV52, HPV58, HPV66, and HPV73. The viral type could not be determined (HPV X) in 1 case (0.6%) of the HPV DNA–positive cervical cancers and double infections were found in 1.7% of the cases. The higher percentage of most aggressive HPV (16/18/45) genotypes was detected in cases diagnosed at younger than 60 years old, whereas these genotypes were less frequent in older patients.ConclusionWe conclude that HPV types 16, 18, and 45 have a very high prevalence in ICC of Uruguayan women. Results provide evidence that 16 of 18 infections are more aggressive, but most cancers could be vaccine preventable.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Raúl Peralta ◽  
Cruz Vargas-De-León ◽  
Augusto Cabrera ◽  
Pedro Miramontes

Human papillomavirus (HPV) has been identified as the main etiological factor in the developing of cervical cancer (CC). This finding has propitiated the development of vaccines that help to prevent the HPVs 16 and 18 infection. Both genotypes are associated with 70% of CC worldwide. In the present study, we aimed to determine the emergence of high-risk nonvaccine HPV after actual vaccination scheme to estimate the impact of the current HPV vaccines. A SIR-type model was used to study the HPV dynamics after vaccination. According to the results, our model indicates that the application of the vaccine reduces infection by target or vaccine genotypes as expected. However, numerical simulations of the model suggest the presence of the phenomenon called vaccine—induced pathogen strain replacement. Here, we report the following replacement mechanism: if the effectiveness of cross-protective immunity is not larger than the effectiveness of the vaccine, then the high-risk nonvaccine genotypes emerge. In this scenario, further studies of infection dispersion by HPV are necessary to ascertain the real impact of the current vaccines, primarily because of the different high-risk HPV types that are found in CC.


2009 ◽  
Vol 83 (6) ◽  
pp. 2756-2764 ◽  
Author(s):  
Susan A. Heilman ◽  
Joshua J. Nordberg ◽  
Yingwang Liu ◽  
Greenfield Sluder ◽  
Jason J. Chen

ABSTRACT High-risk types of human papillomavirus (HPV) are considered the major causative agents of cervical carcinoma. The transforming ability of HPV resides in the E6 and E7 oncogenes, yet the pathway to transformation is not well understood. Cells expressing the oncogene E7 from high-risk HPVs have a high incidence of polyploidy, which has been shown to occur as an early event in cervical carcinogenesis and predisposes the cells to aneuploidy. The mechanism through which E7 contributes to polyploidy is not known. It has been hypothesized that E7 induces polyploidy in response to mitotic stress by abrogating the mitotic spindle assembly checkpoint. It was also proposed that E7 may stimulate rereplication to induce polyploidy. We have tested these hypotheses by using human epithelial cells in which E7 expression induces a significant amount of polyploidy. We find that E7-expressing cells undergo normal mitoses with an intact spindle assembly checkpoint and that they are able to complete cytokinesis. Our results also exclude DNA rereplication as a major mechanism of polyploidization in E7-expressing cells upon microtubule disruption. Instead, we have shown that while normal cells arrest at the postmitotic checkpoint after adaptation to the spindle assembly checkpoint, E7-expressing cells replicate their DNA and propagate as polyploid cells. Thus, abrogation of the postmitotic checkpoint leads to polyploidy formation in E7-expressing human epithelial cells. Our results suggest that downregulation of pRb is important for E7 to induce polyploidy and abrogation of the postmitotic checkpoint.


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