Analysis of HPV1 E4 complexes and their association with keratins in vivo

Virology
J DoorbarS Napthine

Abstract

The HPV1 E4 gene encodes a family of abundant nonstructural late proteins whose role in the virus life cycle is unknown. Their localization to keratin filaments when expressed in cultured epithelial cells has suggested a possible involvement in virus release by disturbing the integrity of the infected cell. Here we show that in naturally occurring HPV1-induced tumors, the majority of the E4 protein (>95%) exists as complexes which do not contain keratins. The identification of discrete species of 34K, 58K, 70K, 88K, and 105K suggests that these are simple multimers of the 17K monomer, with very little of the soluble E4 being present in complexes larger than 140K. The truncated 10/11K E4 species, which comprise the C-terminal domain of E4, exist as trimers and dimers in vivo. Less than 5% of the E4 was present as complexes greater than 140K, and these were found to be insoluble. The 34K (dimer) and 58K (putative trimer) E4 complexes were components of these larger structures. Neither E4 monomers nor E4 complexes could be shown to interact directly with keratins or with keratin filaments although formation of the 105K E4 complex was abolished (and formation of the 58K species enhanced) when keratins were present during E4 synthes...Continue Reading

Citations

Sep 20, 2002·Journal of Virology·Woei Ling PehJohn Doorbar
Jul 2, 2005·Expert Opinion on Emerging Drugs·F X Wilson
Nov 16, 2005·Reviews in Medical Virology·Christy M Hebner, Laimonis A Laimins
Jan 6, 1999·Antiviral Chemistry & Chemotherapy·W C PhelpsD C Lobe
Mar 1, 2003·Veterinary and Comparative Oncology·M S Campo
Oct 16, 2012·Molecular and Cellular Biochemistry·Qingming DingPeter Whyte

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