Cell State as Affecting Susceptibility to a Virus

Abstract

Rabbit skin can be rendered abnormally susceptible to papilloma virus infection by preliminary treatments with a variety of agents. The most effective agents thus far found are 0.3 per cent methylcholanthrene in benzene and a mixture in equal parts of turpentine and acetone, applied four or five times at 2 day intervals. When virus is inoculated into skin altered by these agents, either intradermally or by inunction after scarification, papillomas appear earlier and in greater number than on normal skin, and much higher dilutions give rise to growths. The method provides a means of detecting amounts of virus which cause no papillomas upon inoculation into normal skin. Papilloma virus material which is rubbed into scarified normal or hyperplastic skin is largely lost in the scabbing which ensues, and nearly all of it fails to reach susceptible cells. The preparatory agents which increase the effectiveness of the virus bring about marked epidermal hyperplasia, and the hyperplastic tissue regenerates with greater rapidity when scarified. The agents evidently act in large part by providing young epidermal cells in quantity to the virus, as also by inducing a richer vascularization than ordinary in support of the papillomatous proliferation. It is possible that they also act by providing especially susceptible cells. The implications of the findings are discussed.

Cottontail Rabbit Papillomavirus E8 Protein Is Essential for Wart Formation and Provides New Insights into Viral Pathogenesis

“…In our study, viral DNA was inoculated by a biobalistic method without skin pretreatment. In the experiments of Hu et al (34), skin was chemically pretreated and scarified prior to DNA inoculation, which increases the susceptibility to CRPV infection (23). The resulting epidermal hyperplasia and wound healing involve the release of the slow-cycling, self-renewing epidermal stem cells from the tight microenvironmental control that ensures the homeostasis of the epidermis (1,61).…”

Amino Acid Residues in the Carboxy-Terminal Region of Cottontail Rabbit Papillomavirus E6 Influence Spontaneous Regression of Cutaneous Papillomas

“…NZW outbred rabbits were purchased from Covance (Denver, Pa.), and EIII/JC inbred rabbits were bred and maintained in the animal facilities of the Pennsylvania State University College of Medicine. Prior to viral DNA challenge, the backs of the rabbits were shaved and painted with a mixture of turpentine and acetone (50:50 [vol/vol]) four times in total, once every other day, to make the skin hyperplastic (13,25). Viral DNA constructs (10 g per site) were placed onto scarified sites in 50-l volumes.…”

Wounding prior to challenge substantially improves infectivity of cottontail rabbit papillomavirus and allows for standardization of infection

“…The question was asked whether simple wounding of the skin prior to infection would be adequate. For many years, investigators have shown that wounding confers an advantage to the virus (Friedewald, WF, 1942). Other studies have led to the hypothesis that wounding increases epidermal cells that are the likely targets of CRPV infection .…”