HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell Phenotype
The high incidence of epithelial malignancies in HIV-1 infected individuals is associated with co-infection with oncogenic viruses, such as high-risk human papillomaviruses (HR HPVs), mostly HPV16. The molecular mechanisms underlying the HIV-1-associated increase in epithelial malignancies are not f...
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MDPI AG
2024-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/16/2/193 |
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| author | Alla Zhitkevich Ekaterina Bayurova Darya Avdoshina Natalia Zakirova Galina Frolova Juris Jansons Sona Chowdhury Alexander Ivanov Ilya Gordeychuk Joel M. Palefsky Maria Isaguliants |
| author_facet | Alla Zhitkevich Ekaterina Bayurova Darya Avdoshina Natalia Zakirova Galina Frolova Juris Jansons Sona Chowdhury Alexander Ivanov Ilya Gordeychuk Joel M. Palefsky Maria Isaguliants |
| author_sort | Alla Zhitkevich |
| collection | DOAJ |
| description | The high incidence of epithelial malignancies in HIV-1 infected individuals is associated with co-infection with oncogenic viruses, such as high-risk human papillomaviruses (HR HPVs), mostly HPV16. The molecular mechanisms underlying the HIV-1-associated increase in epithelial malignancies are not fully understood. A collaboration between HIV-1 and HR HPVs in the malignant transformation of epithelial cells has long been anticipated. Here, we delineated the effects of HIV-1 reverse transcriptase on the in vitro and in vivo properties of HPV16-infected cervical cancer cells. A human cervical carcinoma cell line infected with HPV16 (Ca Ski) was made to express HIV-1 reverse transcriptase (RT) by lentiviral transduction. The levels of the mRNA of the E6 isoforms and of the factors characteristic to the epithelial/mesenchymal transition were assessed by real-time RT-PCR. The parameters of glycolysis and mitochondrial respiration were determined using Seahorse technology. RT expressing Ca Ski subclones were assessed for the capacity to form tumors in nude mice. RT expression increased the expression of the E6*I isoform, modulated the expression of <i>E-CADHERIN</i> and <i>VIMENTIN</i>, indicating the presence of a hybrid epithelial/mesenchymal phenotype, enhanced glycolysis, and inhibited mitochondrial respiration. In addition, the expression of RT induced phenotypic alterations impacting cell motility, clonogenic activity, and the capacity of Ca Ski cells to form tumors in nude mice. These findings suggest that HIV-RT, a multifunctional protein, affects HPV16-induced oncogenesis, which is achieved through modulation of the expression of the E6 oncoprotein. These results highlight a complex interplay between HIV antigens and HPV oncoproteins potentiating the malignant transformation of epithelial cells. |
| first_indexed | 2024-03-07T22:11:15Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-07T22:11:15Z |
| publishDate | 2024-01-01 |
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| record_format | Article |
| series | Viruses |
| spelling | doaj.art-9d33d4edd6a24709915ef949880e15da2024-02-23T15:37:27ZengMDPI AGViruses1999-49152024-01-0116219310.3390/v16020193HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell PhenotypeAlla Zhitkevich0Ekaterina Bayurova1Darya Avdoshina2Natalia Zakirova3Galina Frolova4Juris Jansons5Sona Chowdhury6Alexander Ivanov7Ilya Gordeychuk8Joel M. Palefsky9Maria Isaguliants10Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, 119991 Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, 119991 Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, 119991 Moscow, RussiaCentre for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, 119991 Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, 119991 Moscow, RussiaBiomedical Research and Study Centers, LV-1067 Riga, LatviaDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA 94143, USAGamaleya National Research Center for Epidemiology and Microbiology, 123098 Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, 119991 Moscow, RussiaDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA 94143, USAInstitute of Microbiology and Virology, Riga Stradins University, LV-1007 Riga, LatviaThe high incidence of epithelial malignancies in HIV-1 infected individuals is associated with co-infection with oncogenic viruses, such as high-risk human papillomaviruses (HR HPVs), mostly HPV16. The molecular mechanisms underlying the HIV-1-associated increase in epithelial malignancies are not fully understood. A collaboration between HIV-1 and HR HPVs in the malignant transformation of epithelial cells has long been anticipated. Here, we delineated the effects of HIV-1 reverse transcriptase on the in vitro and in vivo properties of HPV16-infected cervical cancer cells. A human cervical carcinoma cell line infected with HPV16 (Ca Ski) was made to express HIV-1 reverse transcriptase (RT) by lentiviral transduction. The levels of the mRNA of the E6 isoforms and of the factors characteristic to the epithelial/mesenchymal transition were assessed by real-time RT-PCR. The parameters of glycolysis and mitochondrial respiration were determined using Seahorse technology. RT expressing Ca Ski subclones were assessed for the capacity to form tumors in nude mice. RT expression increased the expression of the E6*I isoform, modulated the expression of <i>E-CADHERIN</i> and <i>VIMENTIN</i>, indicating the presence of a hybrid epithelial/mesenchymal phenotype, enhanced glycolysis, and inhibited mitochondrial respiration. In addition, the expression of RT induced phenotypic alterations impacting cell motility, clonogenic activity, and the capacity of Ca Ski cells to form tumors in nude mice. These findings suggest that HIV-RT, a multifunctional protein, affects HPV16-induced oncogenesis, which is achieved through modulation of the expression of the E6 oncoprotein. These results highlight a complex interplay between HIV antigens and HPV oncoproteins potentiating the malignant transformation of epithelial cells.https://www.mdpi.com/1999-4915/16/2/193HIV-1reverse transcriptaseHPV16-positive cellsE6*I isoform expressionglycolysismitochondrial respiration |
| spellingShingle | Alla Zhitkevich Ekaterina Bayurova Darya Avdoshina Natalia Zakirova Galina Frolova Juris Jansons Sona Chowdhury Alexander Ivanov Ilya Gordeychuk Joel M. Palefsky Maria Isaguliants HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell Phenotype Viruses HIV-1 reverse transcriptase HPV16-positive cells E6*I isoform expression glycolysis mitochondrial respiration |
| title | HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell Phenotype |
| title_full | HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell Phenotype |
| title_fullStr | HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell Phenotype |
| title_full_unstemmed | HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell Phenotype |
| title_short | HIV-1 Reverse Transcriptase Expression in HPV16-Infected Epidermoid Carcinoma Cells Alters E6 Expression and Cellular Metabolism, and Induces a Hybrid Epithelial/Mesenchymal Cell Phenotype |
| title_sort | hiv 1 reverse transcriptase expression in hpv16 infected epidermoid carcinoma cells alters e6 expression and cellular metabolism and induces a hybrid epithelial mesenchymal cell phenotype |
| topic | HIV-1 reverse transcriptase HPV16-positive cells E6*I isoform expression glycolysis mitochondrial respiration |
| url | https://www.mdpi.com/1999-4915/16/2/193 |
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