The Genomes of Three of Four Novel HPV Types, Defined by Differences of Their L1 Genes, Show High Conservation of the E7 Gene and the URR

Abstract

The DNA genomes of four new human papillomaviruses, HPV 75, HPV 76, HPV 77, and HPV 80, have been cloned, sequenced, and characterized. HPV 75, HPV 76 (both HPV 49-related), and HPV 77 (HPV 29-related) were isolated from benign cutaneous warts and HPV 80 (HPV 15-related) from histologically normal skin. HPV 77 has also been demonstrated in dysplastic warts and squamous cell carcinomas of the skin. The sequence data presented in this study led to a proposed modification of the definition of a new HPV type. The high degree of DNA sequence similarity between the E7 ORF of HPV 77 and HPV 29 (97.7%), as opposed to the E6 (82.8%) and L1 (85.3%) ORFs, might suggest conservation of a specific function or a possible recombinational event. Only the E6 and L1 ORFs of HPV 75 and HPV 76 have a similarity lower than 90%, whereas the DNA sequences of their upstream regulatory regions (URRs) share a similarity of 93%. The E7, E1, and E4 ORFs, as well as the URR of HPV 15 and HPV 80, share sequence similarities higher than 90%. Such a divergence in the similarity between different segments of the virus genomes of closely related HPV types has not been noted to date. A detailed comparative sequence analysis was performed. HPV 75, HPV 76, and HPV 80 revealed features characteristic of truly cutaneous HPV types, whereas HPV 77 shared several characteristics with the mucosal HPV types, some of which may have functional consequences.

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

“…Although we demonstrate in the current study that Th responses can be cross-reactive between different PV L1 proteins, as would be predicted by the Ͼ70% sequence homology between the different PV genotypes (50) and the relative promiscuity of MHC class II for Th peptides (32,51), the observed lack of cross-inhibition between VLPs suggests that the demonstrated T cell cross-reactivity between PV genotypes may be of little biological relevance for induction of regulatory T cells. This observation is of some importance, as prior immunity to one PV genotype, induced by infection or prophylactic vaccination, would frequently be present in subjects infected with an unrelated PV genotype, and clearance of the new PV infection is thought to depend on induction of appropriate cell-mediated immune responses to PV protein epitopes not shared between PV types.…”

RETRACTED ARTICLE: Human papillomavirus type 77 E6 protein selectively inhibits p53-dependent transcription of proapoptotic genes following UV-B irradiation

“…Studies have shown that 90% of tumours in EV patients show the presence of HPVs, particularly types 5 and 8, which are commonly referred to as EV-associated types (Orth, 1986). RTR patients are instead subject to mixed infection with many different cutaneous types, including the recently isolated type HPV 77 (Delius et al, 1998;Surentheran et al, 1998;de Villiers et al, 1999;Harwood et al, 2000). It is important to note that although the EV types are included in the cutaneous group, they are distant phylogenetically from other cutaneous types and it has recently been argued that they may define a distinct subgroup within the cutaneous branch (Orth et al, 2001).…”

RETRACTED ARTICLE: E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage

“…For these experiments we chose three di erent HPV types: the EVassociated HPV5 (group B1); a low risk cutaneous type, HPV10 (group A2); and HPV77, a group A2 type related to HPV10 which was originally identi®ed in both warts and SCCs of a renal transplant recipient (Shamanin et al, 1994;Delius et al, 1998). The E6 gene from each of the viruses was ampli®ed by PCR and subcloned into the expression vector pcDNA3 and were veri®ed by DNA sequencing.…”