The Process of HPV Infection Leading to Genital Warts: There are two perspectives on the process by which HPV infection leads to the onset of genital warts. One perspective suggests that it is due to active proliferation of basal cells; the other perspective argues that the speed of basal cell proliferation is normal, but delayed cellular maturation prevents timely maturation and keratinization of epidermal cells, leading to cell accumulation presenting as "proliferative-like" changes.
Some scholars have observed the entire process of gene transcription, tissue changes, and the occurrence of genital warts after HPV infection in experiments. Stoler et al. infected human foreskin tissue with HPV type 11, then transplanted it under the renal capsule of nude mice. They took small amounts of xenograft live tissue every two weeks for a total of 14 weeks. The harvested live tissues were fixed with formalin, embedded in paraffin, sectioned continuously, and examined under a light microscope for morphological changes. Immunohistochemical methods were used to detect HPV antigens, and RNA probes labeled with 3H were used for in situ hybridization to detect viral DNA replication and the transcription of several main mRNAs. It was found that at the 4th week post-transplantation, the transcription of E4 and E5 first appeared. By the 6th to 8th week, other early region genes also underwent transcription. At the 6th week, the xenograft experienced drastic changes, with increased cell proliferation, viral DNA replication, and vigorous transcription of mRNAs from both the E and L regions until reaching a plateau. By the 10th to 12th week, experimental genital warts were indistinguishable from naturally occurring ones in both appearance and histology, characterized by thickening of the epidermal spinous layer, prominent clear keratohyalin granules in the granular layer, vacuolated cells in the spinous and granular layers, and some showing intranuclear basophilic inclusions. These results indicate that the high cell proliferation and morphological characteristics of genital warts are direct results of viral gene activity. The transcription of the E region of HPV11 increased with the survival period and cell differentiation of the cells and persisted throughout the entire experiment, which is different from other DNA viruses, especially the relatively abundant content of mRNAs encoding E4 and E5 being maintained. Conversely, viral DNA replication, synthesis of L region mRNA, and production of HPV antigens were limited to well-differentiated keratinocytes in the epidermis, leading some scholars to speculate that there may be a keratinocyte-specific factor necessary for HPV proliferation.
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