Detection of adeno-associated virus type 2 genome in cervical carcinoma

Zheng, B H; Xd, Li; Wiklund, Fredrik; Chowdhry, Sudhir; Ángström, T; Hallmans, Göran; Dillner, Joakim; Kl, Wallin

doi:10.1038/sj.bjc.6603179

Cited by 5 publications

(4 citation statements)

References 35 publications

(49 reference statements)

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“…In this study, we used the AAV2 serotype to transfer sgRNAs into HeLa cells. Previous studies have shown the efficiency of this serotype for gene transfer into cervical cancer cells 22 , 23 .…”

Section: Discussionmentioning

confidence: 96%

Antiproliferative effects of AAV-delivered CRISPR/Cas9-based degradation of the HPV18-E6 gene in HeLa cells

Noroozi

Shamsara

Valipour

et al. 2022

Sci Rep

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Human papillomavirus infections are associated with most cervical cancers, which are the fourth most common cancer in women. HPV-E6 protein binds to protein p53 and inhibits its function, leading to the switching of normal cells toward cancer cells. Here, we disrupted the HPV-E6 gene and investigated its effects on the proliferation and apoptosis of HeLa cells. The HPV18-E6 gene was targeted with two designed sgRNAs cloned into an AAV-CRISPR-based plasmid. The AAV-E6-CRISPR/Cas9 virions were prepared and titrated in HEK293t cells. The cleavage created in the HPV-E6 gene was detected using the T7E1 assay. Cell cycle profiling, MTT assay, and annexin V/PI staining were performed. Also, the p53 protein level was measured by Western blotting. Our data showed that disruption of the HPV-E6 gene led to increased cell apoptosis and decreased cell proliferation. A significant accumulation of infected cells in sub-G1 phase was observed in the cell profiling assay. Also, HPV-E6 gene disruption resulted in a significant increase in the level of P53 protein. Our findings indicated that AAV-mediated delivery of CRISPR/Cas9 can effectively target the HPV-E6 gene in HeLa cells, and its antiproliferative effects may provide therapeutic benefits of local administration of this gene-editing system for HPV-related cervical cancers.

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Section: Discussionmentioning

confidence: 96%

Antiproliferative effects of AAV-delivered CRISPR/Cas9-based degradation of the HPV18-E6 gene in HeLa cells

Noroozi

Shamsara

Valipour

et al. 2022

Sci Rep

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“…A case control study in pregnant and non-pregnant women found that AAV infection have any impact on cervical intraepithelial neoplasia development [65]. Moreover, a retrospective case control study by Zheng et al (2006) found a low proportion of cervical cancer biopsies containing AAV genomes and no evidence that the presence of AAV in cervical smears of healthy women would be associated with a reduced risk of cervical cancer [66]. Finally, an Iranian study from 2017 detected a low proportion of cervical biopsies containing AAV genome (14.8% cervical cancer cases and 14% healthy controls) and no significant difference in correlation between HPV and cervical cancer in the presence or absence of AAV infection was found [67].…”

Section: Aav Infection and Cervical Cancermentioning

confidence: 99%

“…These data point out that HPV could indeed be an AAV helper virus and that AAV as such can be considered sexually transmissible. [ 66 ] 2006 Sweden Cases = 104 Matched control = 104 Cervical smear; cervical tissue At baseline, 2% of case-women and 3% of control-women were positive for AAV type 2 DNA. At the time of cancer diagnosis, 12% of case-women and 3% of matched control-women were positive for AAV DNA.…”

Section: Introductionmentioning

confidence: 99%

Adeno-associated virus infection and its impact in human health: an overview

Sant’Anna

Araújo

2022

Virol J

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Discovered as a contaminant of adenovirus stocks in the 1960s, adeno-associated virus (AAV) is a mono-stranded DNA virus that depends on helper factors to replicate. Even though AAV is endemic in the human population (35–80%), it is remarkable that many issues concerning the natural infection by this virus remain unanswered. In this study, we reflect on the main basic aspects of AAV biology and provide an overview of the studies exploring the impact of AAV infection on human health, focusing on three major research areas including, (i) cervical and (ii) liver cancer, and (iii) reproductive system disorders. Conflicting results have been obtained into the association of AAV infection with the occurrence of adverse reproductive outcomes, such as placental complications, spontaneous abortion, and fertility disorders, or with a protective role in HPV-related cervical carcinogenesis. Noteworthy, recent reports have identified AAV insertional mutagenesis as a novel risk factor for the development of hepatocellular carcinoma. This latest finding raises concern regarding the widespread usage of AAV vectors in liver-targeted gene therapy.

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“…This will allow for better manipulation of AAV replication and, ultimately, should greatly boost rAAV production. Furthermore, while certain groups fail to see a correlation [7-9], the vast majority of epidemiologic, animal, and tissue culture studies strongly suggest that AAV inhibits the carcinogenesis process [10-29]. Moreover, there is a long history of AAV functioning as an autonomous parvovirus during specific circumstances.…”

Section: Introductionmentioning

confidence: 99%

Cervical cancer isolate PT3, super-permissive for adeno-associated virus replication, over-expresses DNA polymerase δ, PCNA, RFC and RPA

et al. 2009

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BackgroundAdeno-associated virus (AAV) type 2 is an important virus due to its use as a safe and effective human gene therapy vector and its negative association with certain malignancies. AAV, a dependo-parvovirus, autonomously replicates in stratified squamous epithelium. Such tissue occurs in the nasopharynx and anogenitals, from which AAV has been clinically isolated. Related autonomous parvoviruses also demonstrate cell tropism and preferentially replicate in oncogenically transformed cells. Combining these two attributes of parvovirus tropism, squamous and malignant, we assayed if AAV might replicate in squamous cervical carcinoma cell isolates.ResultsThree primary isolates (PT1-3) and two established cervical cancer cell lines were compared to normal keratinocytes (NK) for their ability to replicate AAV. One isolate, PT3, allowed for high levels of AAV DNA replication and virion production compared to others. In research by others, four cellular components are known required for in vitro AAV DNA replication: replication protein A (RPA), replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and DNA polymerase delta (POLD1). Thus, we examined PT3 cells for expression of these components by DNA microarray and real-time quantitative PCR. All four components were over-expressed in PT3 over two representative low-permissive cell isolates (NK and PT1). However, this super-permissiveness did not result in PT3 cell death by AAV infection.ConclusionThese data, for the first time, provide evidence that these four cellular components are likely important for AAV in vivo DNA replication as well as in vitro. These data also suggest that PT3 will be a useful reagent for investigating the AAV-permissive transcriptome and AAV anti-cancer effect.

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Detection of adeno-associated virus type 2 genome in cervical carcinoma

Cited by 5 publications

References 35 publications

Antiproliferative effects of AAV-delivered CRISPR/Cas9-based degradation of the HPV18-E6 gene in HeLa cells

Antiproliferative effects of AAV-delivered CRISPR/Cas9-based degradation of the HPV18-E6 gene in HeLa cells

Adeno-associated virus infection and its impact in human health: an overview

Cervical cancer isolate PT3, super-permissive for adeno-associated virus replication, over-expresses DNA polymerase δ, PCNA, RFC and RPA

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