Microcheck 145

Animal tumor viruses can transform animal cells growing in culture. Retroviruses cause tumors in animals by inserting an oncogene, which alters normal cell growth.

■ Distinguish between oncogenes and proto-oncogenes.

■ List four properties of transformed cells in culture.

■ Why is reverse transcriptase not found in normal cells?

14.6 Viruses and Human Tumors tion in the entering single-stranded RNA molecule be converted into a double-stranded DNA molecule by the viral enzyme reverse transcriptase. This DNA is then integrated into the host cell genome, where it is expressed.

What is the nature of the transforming genes? These genes are termed oncogenes, (from the word onkos, which means "mass" or "lump"). They are mutant forms of the normal cell's proto-oncogenes. The mutation modifies the biochemical properties of the protein coded by the oncogene so that an oncogene integrated into the genome of a cell interferes with the normal intracellular control functions of the proto-oncogene. This disruption results in tumor formation. More than 60 oncogenes have been discovered in retroviruses thus far; a few are listed in table 14.10. Different tumor viruses contain different oncogenes that function somewhat differently. They are, however, all involved in regulating normal cell growth.

The best available evidence suggests that oncogenes originated from proto-oncogenes that were "captured" by the retrovirus in the course of being excised from the host genome. Once inside the virus, the proto-oncogene underwent mutations that converted it into an oncogene. The temperate phage system in bacteria provides an excellent analogy for this "capture'' hypothesis. Recall that temperate phages integrated into the bacterial host chromosome can incorporate a piece of bacterial DNA into their chromosome when the phage DNA is excised from the host chromosome. The virus can then transfer the bacterial DNA to other bacteria by transduction. By analogy, retroviruses, which also integrate into the chromosome of the host, could very well carry along a proto-oncogene from the host in the process of excision from the host chromosome. ■ temperate phage, p. 329 ■ transduction, pp. 205,333

Most human tumors are not caused by viruses, despite intensive efforts to prove otherwise. These numbers are increasing, however, because of the common occurrence of a viral-induced tumor, Kaposi's sarcoma, in AIDS patients. Further, as discussed in A Glimpse of History, some studies suggest that the SV40 virus may cause a variety of tumors. The majority of human tumors appear to be caused by mutations in either proto-oncogenes or other genes. About 30% are estimated to be due to activation of a particular mutant proto-oncogene.

Considering all viruses, double-stranded DNA viruses are the main cause of virus-induced tumors in humans (table 14.11). DNA tumor viruses interact with their host cells in one of two ways. They can go through a productive infection in which they lyse the cells, or they can transform the cells without killing them. The cancers caused by the DNA viruses result from the integration of all or part of the virus genome into the host chromosome. Following integration, the transforming genes are expressed, resulting in uncontrolled growth of the host cells. Thus, these cases of abnormal growth are analogous to lysogenic conversion observed in certain temperate phage infections of bacteria. In both cases, the expression of viral genes integrated into the host's chromosome confers new properties on the host cells. ■ lysogenic conversion, p. 331

In the case of some DNA viruses, such as papillomaviruses and herpesviruses, the viral DNA is not integrated but apparently replicates as a plasmid. In the case of the papillomaviruses, on rare occasions, the plasmid may integrate into the host chromosome and this may cause tumors. Certain types of human papillomavirus are linked with most cases of cervical cancer, as well as with vulval, penile, and anal cancers. ■ papillomavirus, p. 654 ■ herpesvirus, p. 344 ■ plasmid, p. 209

Kaposi's sarcoma, a cancer of the skin and internal organs common in AIDS patients, is caused by a herpesvirus. How this particular virus causes normal cells to become tumorous is not known. Note that in all cases of virus-induced tumors, the virus

Nester-Anderson-Roberts: I II. The Microbial World I 14. Viruses, Prions, and I I © The McGraw-Hill

Microbiology, A Human Viroids: Infectious Agents Companies, 2003

Perspective, Fourth Edition of Animals and Plants

Chapter 14 Viruses, Prions, and Viroids: Infectious Agents of Animals and Plants

Table 14.11 Viruses Associated with Cancers in Humans

Virus

Type of Nucleic Acid

Kind of Tumor

Human papillomaviruses (HPV)

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