Viruses, Viroids, and Prions |
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Several pieces of evidence pointed to the transmission of cancer by viruses in animals.
1908 - Chicken leukemia
1911 - Rous chicken sarcoma
1936 - Virus-induced adenocarcinoma in mice
1972 - First human cancer-causing virus discovered and isolated.
Oncogenes - genes involved in tumor formation, first identified as part of viral genomes. It was later shown that the viral oncogenes were actually derived from animal cells.
Oncogenes may be activated (to function abnormally or without normal controls) by mutagenic chemicals, radiation, and viruses. Activation events may include mutation, transduction, translocation, and amplification.
Oncogenic viruses are capable of producing tumors in animals.
Oncogenic viruses integrate into host cell DNA and may cause transformation of host cells.
Transformed cells lose contact inhibition, contain virus-specific antigens (tumor-specific transplantation antigen (TSTA)on the cell surface or T antigen in the nucleus), exhibit chromosomal abnormalities, and can produce tumors when injected into susceptible animals.
Tumor Types:
Benign - tumors that generally don’t spread, can be removed, and aren’t life threatening
Malignant – invasive, generally aggressive tumors that are life threatening
Characteristics of Benign and Malignant Tumors
Organization (differentiation and anaplasia)
Differentiation: the extent to which tumor cells resemble the cell of origin in both appearance and function
Anaplasia: undifferentiated, cells appear almost embryonic
Pleomorphism: variation in shape and size
Dysplasia: disorganized but non-neoplastic
The relationship between anaplasia and growth rate and specialized function is inverse – the more anaplastic and the faster growing cells are the less likely to have specialized function
Benign tumors tend to be more differentiated, exhibit dysplasia, and the cells aren't usually pleomorphic.
Malignant tumors tend to exhibit anaplasia and pleomorphism.
Rate of growth
Benign tumors generally grow slowly
Malignant tumors exhibit a correlation between rate of growth and degree of differentiation
May have periods of slow growth followed by rapid growth, may spontaneously regress to due central necrosis and inability to provide nutrition
Local invasion
Benign tumors are usually demarcated and often encapsulated
Malignant tumors are invasive; penetrate surrounding tissue
Metastasis
Development of secondary tumors distant from the site of the original tumor, characteristic of malignant tumors
Found among:
Adenoviruses
Herpesviruses
EBV
Burkitt’s lymphoma Nasopharyngeal carcinoma Herpes simplex
Association with cervical cancer Poxviruses
Papovaviruses
Human papilloma viruses (especially HPV-16) - cervical cancer
Hepadnaviruses
HBV - hepatocellular carcinoma
HIV
HTLV-1 and HTLV-2 are associated with human leukemia and lymphomas.
Reverse transcriptase produces viral DNA that integrates into host genome as a provirus.