In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential - PubMed (original) (raw)

In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential

M S Barbosa et al. J Virol. 1991 Jan.

Abstract

Human papillomavirus type 16 (HPV-16) and HPV-18 are often detected in cervical carcinomas, while HPV-6, although frequently present in benign genital lesions, is only rarely present in cancers of the cervix. Therefore, infections with HPV-16 and HPV-18 are considered high risk and infection with HPV-6 is considered low risk. We found, by using a heterologous promoter system, that expression of the E7 transforming protein differs between high- and low-risk HPVs. In high-risk HPV-16, E7 is expressed from constructs containing the complete upstream E6 open reading frame. In contrast, HPV-6 E7 was efficiently translated only when E6 was deleted. By using clones in which the coding regions of HPV-6, HPV-16, and HPV-18 E7s were preceded by identical leader sequences, we found that the ability of the E7 gene products to induce anchorage-independent growth in rodent fibroblasts correlated directly with the oncogenic association of the HPV types. By using an immortalization assay of normal human keratinocytes that requires complementation of E6 and E7, we found that both E6 and E7 of HPV-18 could complement the corresponding gene from HPV-16. However, neither E6 nor E7 from HPV-6 was able to substitute for the corresponding gene of HPV-16 or HPV-18. Our results suggest that multiple factors, including lower intrinsic biological activity of E6 and E7 and differences in the regulation of their expression, account for the low activity of HPV-6, in comparison with HPV-16 and HPV-18, in in vitro assays. These same factors may, in part, account for the apparent difference in oncogenic potential between these viruses.

PubMed Disclaimer

Cited by

Recurrent respiratory papillomatosis.
Venkatesan NN, Pine HS, Underbrink MP. Venkatesan NN, et al. Otolaryngol Clin North Am. 2012 Jun;45(3):671-94, viii-ix. doi: 10.1016/j.otc.2012.03.006. Otolaryngol Clin North Am. 2012. PMID: 22588043 Free PMC article. Review.
Antibodies against early proteins of human papillomaviruses as diagnostic markers for invasive cervical cancer.
Meschede W, Zumbach K, Braspenning J, Scheffner M, Benitez-Bribiesca L, Luande J, Gissmann L, Pawlita M. Meschede W, et al. J Clin Microbiol. 1998 Feb;36(2):475-80. doi: 10.1128/JCM.36.2.475-480.1998. J Clin Microbiol. 1998. PMID: 9466762 Free PMC article.
Inhibition of p53 DNA binding by human papillomavirus E6 proteins.
Lechner MS, Laimins LA. Lechner MS, et al. J Virol. 1994 Jul;68(7):4262-73. doi: 10.1128/JVI.68.7.4262-4273.1994. J Virol. 1994. PMID: 8207801 Free PMC article.
Mutant p53 can substitute for human papillomavirus type 16 E6 in immortalization of human keratinocytes but does not have E6-associated trans-activation or transforming activity.
Sedman SA, Hubbert NL, Vass WC, Lowy DR, Schiller JT. Sedman SA, et al. J Virol. 1992 Jul;66(7):4201-8. doi: 10.1128/JVI.66.7.4201-4208.1992. J Virol. 1992. PMID: 1318401 Free PMC article.
Interaction of zyxin, a focal adhesion protein, with the e6 protein from human papillomavirus type 6 results in its nuclear translocation.
Degenhardt YY, Silverstein S. Degenhardt YY, et al. J Virol. 2001 Dec;75(23):11791-802. doi: 10.1128/JVI.75.23.11791-11802.2001. J Virol. 2001. PMID: 11689660 Free PMC article.

References

1. J Virol. 1986 Jan;57(1):353-6 - PubMed
1. J Virol. 1989 Jun;63(6):2650-6 - PubMed
1. J Virol. 1987 Aug;61(8):2581-8 - PubMed
1. Nature. 1985 Mar 7-13;314(6006):111-4 - PubMed
1. J Virol. 1989 Oct;63(10):4417-21 - PubMed

In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential - PubMed (original) (raw)