EVIDENCE FOR DISSOCIATION OF HISTONE MESSENGER-RNA EXPRESSION FROM CELLULAR PROLIFERATION IN CUTANEOUS HUMAN PAPILLOMAVIRUS INFECTION

Replication of human papillomavirus (HPV) is thought to require the ex pression of components of the host cell DNA replication apparatus, The expression of the mRNA encoding the DNA replication-dependent histone s H2B, H3, and H4 was investigated in a series of verrucae using an FI TC-labelled oligonucleotide cocktail for in situ hybridization, to exp lore the possibility of HPV inducing the transcription of host cell hi stones. In contrast to normal epidermis, in,which the majority of hist one mRNA labelling was confined to basal cells, a bimodal distribution of histone positivity was observed in all verrucae, In addition to ba sal hyperproliferation-associated labelling, numerous positive supraba sal cells were found within the stratum spinosum. By contrast, in anot her hyperproliferative lesion, psoriasis, the labelling pattern was si milar to that found in the normal controls, with characteristic basal hyperproliferation but no evidence of suprabasal labelling. The presen ce of HPV replication in every verruca and its absence from all contro ls of normal and psoriatic skin were demonstrated immunohistochemicall y, using a polyclonal antibody to the viral capsid proteins, It is pro posed that the presence of histone mRNAs in differentiated suprabasal keratinocytes of verrucae is due to the virus turning on parts of the cellular apparatus in order for it to replicate in the absence of cell ular proliferation, The results also emphasize that when assessing pro liferation with in situ hybridization for histone mRNA, the possibilit y of HPV causing the labelling of non-proliferating cells should be co nsidered.