Chapter 12 : Beyond the Provirus: from Howard Temin's Insights on Rous Sarcoma Virus to the Study of Epstein-Barr Virus, the Prototypic HumanTumor Virus

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This chapter focuses on the development of one's understanding of carcinogenesis mediated by avian retroviruses, to which Howard Temin contributed so much. This understanding, coupled with the associated study of retroviruses in general, has been essential to dealing effectively with human disease. It also outlines current appreciation of human tumor viruses, using Epstein-Barr virus (EBV) as a model. Human tumor viruses are less efficient pathogens than most of the well-studied avian oncogenic retroviruses. Howard Temin refined a transformation assay for Rous sarcoma virus (RSV) such that it became a standard method for detecting and measuring the transforming abilities of different viruses in cell culture. Avian leukosis viruses (ALVs) provide one example of weakly transforming viruses. These viruses formerly often infected commercial flocks of chickens, in which they were propagated either vertically or horizontally. Four human tumor viruses-EBV (a herpesvirus), hepatitis B virus (HBV), human papilloma virus types 16 (HPV-16), -18, -31, and -33, and human T-cell leukemia virus type 1 (HTLV-1; a retrovirus)-have been studied sufficiently to be considered in this chapter. A fifth, hepatitis C virus, has been identified, but virologic studies of it are only now beginning. The outcome of infection with some human tumor viruses can be profoundly affected by the immune response of the host. The four human tumor viruses (EBV, HBV, HPV, and HTLV-1 ) vary in the cell types they infect, in the times between infection and development of cancers, and in the mechanisms by which they induce and/or maintain proliferation of infected cells.

Citation: Sugden B. 1995. Beyond the Provirus: from Howard Temin's Insights on Rous Sarcoma Virus to the Study of Epstein-Barr Virus, the Prototypic HumanTumor Virus, p 161-184. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch12
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Figure 1

Synopsis of steps proposed to occur between infection with these different model tumor viruses and development of their associated tumors. The order in which the steps occur is consistent with current understanding of the etiologies of these virus-associated tumors but is hypothetical. Ig, immunoglobulin.

Citation: Sugden B. 1995. Beyond the Provirus: from Howard Temin's Insights on Rous Sarcoma Virus to the Study of Epstein-Barr Virus, the Prototypic HumanTumor Virus, p 161-184. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch12
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Image of Figure 2
Figure 2

Synopsis of the shared and different steps proposed to occur between infection with EBV and the development of a benign lymphoproliferative disease (infectious mononucleosis) or a malignant one (Burkitt's lymphoma). Ig, immunoglobulin.

Citation: Sugden B. 1995. Beyond the Provirus: from Howard Temin's Insights on Rous Sarcoma Virus to the Study of Epstein-Barr Virus, the Prototypic HumanTumor Virus, p 161-184. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch12
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Image of Figure 3
Figure 3

Map of the EBV genome, depicting transcripts expressed during the latent phase of the viral life cycle (adapted from reference ). The circle represents the circular DNA of EBV joined at the terminal repeats (TR), as occurs in latently infected cells. The letters and slash marks in the circle denote fragments of EBV DNA generated by digestion with BamHI endonuclease. oriP and oriLyt are the two origins of DNA replication of EBV; oriP is used during the latent phase of the viral life cycle, and oriLyt is used during the lytic phase. Arrows represent start sites for transcription used during the EBV latent phase and considered in this chapter. Open boxes following the arrows are coding sequences for translation of EBV latent genes (EBNA-LP is made up of the repeats within BamW, while EBNA-2 is made up of the single exon within BamY and BamH), and the dashed lines between them represent introns and untranslated exons.

Citation: Sugden B. 1995. Beyond the Provirus: from Howard Temin's Insights on Rous Sarcoma Virus to the Study of Epstein-Barr Virus, the Prototypic HumanTumor Virus, p 161-184. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch12
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