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Development of Shope Papilloma Virus Induced Growth in Tarred Rabbit Ears

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Overview and Background

The myxoma virus, a kind of poxvirus, is the cause of myxomatosis. Natural hosts include wild brush rabbits (Sylvilagus bachmani) in California and wild jungle rabbits, or tapeti (Sylvilagus brasiliensis), in South and Central America. Myxoma virus induces a minor, self-limiting cutaneous fibroma in several rabbit species, but no systemic illness develops.

However, myxomatosis is a severe and nearly always deadly systemic disease that affects European wild rabbits, which includes domestic rabbits (Oryctolagus cuniculi).

Shope Papilloma Virus 

Cottontail rabbits (Sylvilagus floridanus) and wild California brush rabbits (S bachmani) are hosts to the Shope papilloma virus (family Papovaviradae). Ticks and other biting arthropods are the mechanical carriers of this oncogenic DNA virus. Although uncommon, domestic rabbits (O cuniculus) can become infected and develop many hyperkeratotic horn-like lesions, primarily on the neck, shoulders, and around the ears. In wild rabbits, manual removal leads to healing; nevertheless, in domestic rabbits

Effect of Papilloma Virus on Tarred Rabbit Skin

Rabbits that have previously had tar on their ears for one to three months develop rapid, frequently massive growths on the tarred skin when the Shope Papilloma Virus is put into their bloodstream. A few are squamous cell carcinomas, which are typically numerous and often metastatic. We examined the occurrence in ninety tarred controls and over seventy rabbits. None of the latter have experienced cancerous growths.

Virus-Induced Tumor Growth and Transformation

Many of the growths originate in areas with no discernible localized proliferation. However, some are derived from pre-existing tar warts, which begin to grow quickly, change in appearance, and occasionally show signs of malignancy. The majority of common tar warts vanish and the remaining ones turn dormant when tarring is stopped, whereas virus-stimulated warts continue to grow. 

A review of several hundred specimens has revealed that some are currently carcinomatous but may transform into characteristic virus papillomas; others have developed into hybrids that are not typical tar tumors or typical virus tumors but rather unusual papillomas with a malignant appearance that nearly instantly transform into squamous cell carcinomas. Many of the warts, despite being significantly induced by the virus (as indicated by weekly measurements of their dimensions), nevertheless, still have the appearance of tar tumors.

In Vitro Infection of Tar Warts with Papilloma Virus

The virus gets a chance to cause infection tar warts in vitro to gather further information. The warty tissue was removed from the ears, a section was cut out, and equal amounts of the hashed leftover material were steeped for a few minutes in Tyrode and in a Berkefeld filtrate of Tyrode that contained a strong virus, respectively. Following this, they were implanted in the host’s subcutaneous tissue and leg muscles at the appropriate times. Each rabbit was given this treatment for four or five wart materials in addition to some tarred skin that was free of warts. 

Tarring was continued in the following days due to the assumption that it would generally promote proliferation. Warts that were used turned out to be the well-known tar papillomas and carcinoids, so named because even while they continue to tar, they eventually disappear or return to the benign, papillomatous form, despite possessing the histology of carcinomas and frequently ulcerating and expanding into the ear.

The outcome of Implants in Animals 

Nine animals that had implants died between 38 and 64 days, while one died 20 days later. Neither the skin specimens nor any of the 44 wart components immersed in Tyrode had produced a growth. Five of the former and four of the latter had little cysts bordered with regular, stratified squamous epithelium, with the remaining two undergoing resorption. Similar results have been observed by Ferrero.

Effects of Papilloma Virus Infection on Tissues and Implants

The result with the tissues infected with the virus was very different. Then, as with direct implantation of the Shope papilloma, the skin fragments periodically gave birth to nodules of papillomatous tissue. Of the 24 tar papillomas, 15 implanted, produced similar nodules, 4 produced nothing, and 3 resulted in little cysts similar to the ones just mentioned. One developed into a malignant papilloma that was very different from the original wart, while the other became a multicentric growth that kept the original wart’s unique morphology. 

Of 20 carcinoids containing the virus, 8 produced nodules associated with Shope papillomatosis, while 9 had no results at all. Carcinomatous aspect growths appeared in the remaining three cases. In two of these cases, the morphological features of the original carcinoid had been preserved, and despite their invasion, the growths were tiny. It appeared to be a malignant malignancy, with just a small resemblance to the initial carcinoid and no resemblance to those Shope papillomas that infiltrate the muscle in which they are implanted. The third was big, anaplastic, and particularly aggressive.

Biopsy Findings and Tumor Transformation in Implanted Warts

In four out of the five cases, the warts that gave rise to the malignant growths during implantation were found to be big upon biopsy, with a significant portion of their tissue remaining in place. One of them kept growing slowly after the tarring was halted, but it histologically transformed into a benign papilloma, and the other three vanished. The largest to vanish measured 2.3 cm in diameter and had penetrated the ear when roughly 10% of it was removed for steeping. While the bits exposed to the virus developed into the massive, deadly tumor previously indicated, the bits submerged in Tyrode showed no growth at all.

Role of Papilloma Virus in Tumor Morphology and Growth

It is well known that tumors can serve as breeding grounds for foreign viruses. While some result in necrosis or the creation of inclusion bodies, others cause no discernible alteration. The Papilloma Virus does not result in inclusions, but it does produce morphological changes in many tar tumors, accelerates their active growth, often plays a decisive role in their survival, and in certain cases, gives them the appearance of carcinomas.

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