Virus Genes

Lineage and sublineage analysis of human papillomavirus types 51 and 59 in Iranian women

The current study aimed to investigate the sequence variations of HPV 51 and 59 in normal cervical cells and premalignant/malignant lesions of the cervix to know the common variants of HPV 51 and HPV 59 circulating in Iran. To do this, eighty-five samples that were infected by HPV 51 or HPV 59 were investigated using hemi-PCR to amplify the E6 gene followed by sequencing. Our findings indicated that lineages A and B were detected in 80.4% and 19.6% of HPV 51-positive cases, respectively. Among samples infected with HPV 59, 32.2% belonged to lineage A and 67.8% were classified with lineage B. In conclusion, our results showed that lineage A of HPV 51 and lineage B of HPV 59 are more prevalent and distributed in Iran.

Hyperactivation of p53 using CRISPRa kills human papillomavirus-driven cervical cancer cells

Clinical and pre-clinical work for a number of cancer types has demonstrated relatively positive outcomes and effective tumour regression when the level and function of p53, a well-established tumour suppressor, is restored. Human papillomavirus (HPV)-driven cancers encode the E6 oncoprotein, which leads to p53 degradation, to allow the carcinogenic process to proceed. Indeed, there have been several attempts to revive p53 function in HPV-driven cancers by both pharmacological and genetic means to increase p53 bioavailability. Here, we employed a CRISPR activation (CRISPRa) approach to overcome HPV-mediated silencing of p53 by hyperexpressing the p53 gene promoter. Our data show that CRISPRa-mediated hyperexpression of p53 leads to HPV

Activating transcription factor 3 mediates apoptotic functions through a p53-independent pathway in human papillomavirus 18 infected HeLa cells

Activating transcription factor 3 (ATF3) is the first p53 stability regulator that interferes with the ubiquitination of p53. However, the E6 oncoprotein of high-risk human papillomaviruses (HPVs) binds to and induces proteasome-dependent degradation of the host p53 protein. Herein, we investigate the effects of ATF3 overexpression on cell cycle progression and apoptosis in HPV-18-infected HeLa cells, and further examine whether ATF3 could alter the apoptosis level of HeLa cells through the inhibition of E6-mediated p53 degradation. Cytological function of HeLa cells prior and subsequent to the overexpression of ATF3 was assessed using cell cycle and annexin V/PI flow cytometry analysis. Western blotting assays revealed no significant effect of ATF3 on the levels of p53 and E6 in HeLa cells. However, annexin V staining demonstrated increases in apoptosis. ATF3 acts as a tumor suppressor factor in HPV18-related cervical cancer which mediates apoptotic functions through a p53-independent pathway.