Oncogenic viruses (Human cancer viruses)
Viruses are considered to be factors in the development of several types of
human tumors. They include human papillomaviruses, Epstein-Barr virus, human
herpesvirus 8, hepatitis B virus, hepatitis C virus, and two human retroviruses plus
several candidate human cancer viruses.
Table 1. Association of Viruses with Human Cancers.
Virus Family
Virus
Papillomaviridae Human papillomaviruses
Herpesviridae
Human Cancer
Genital tumors
Squamous cell carcinoma
Oropharyngeal carcinoma
EB virus
Human herpesvirus 8
Nasopharyngeal
carcinoma
Burkitt's lymphoma
Hodgkin's disease
B cell lymphoma
Kaposi's sarcoma
Hepadnaviridae Hepatitis B virus
Hepatocellular carcinoma
Retroviridae
HTL virus
Adult T cell leukemia
Human immunodeficiency
virus
AIDS-related malignancies
Hepatitis C virus
Hepatocellular carcinoma
Flaviviridae
General Features of Viral Carcinogenesis
These features are summarized in Table 2
Table 2 Features of Viral Carcinogenesis.
1. Viruses can cause cancer in animals and humans.
2. Tumor viruses frequently establish persistent infections in natural hosts.
3. Host factors are important determinants of virus-induced tumorigenesis.
4. Viruses are seldom complete carcinogens.
5. Virus infections are more common than virus-related tumor formation.
6. Long latent periods usually elapse between initial virus infection and tumor
appearance.
7. Viral strains may differ in oncogenic potential.
8. Viruses may be either direct- or indirect-acting carcinogenic agents.
9. Oncogenic viruses modulate growth control pathways in cells.
10. Animal models may reveal mechanisms of viral carcinogenesis.
11. Viral markers are usually present in tumor cells.
12. One virus may be associated with more than one type of tumor.
Mechanisms of Action by Human Cancer Viruses
Tumor viruses mediate changes in cell behavior by means of a limited amount of
genetic information. There are two general patterns by which this is accomplished:
The tumor virus introduces a new "transforming gene" into the cell (direct-acting),
or the virus alters the expression of a preexisting cellular gene or genes (indirectacting). In either case, the cell loses control of normal regulation of growth
processes. DNA repair pathways are frequently affected, leading to genetic
instability and a mutagenic phenotype.
Cellular transformation may be defined as a stable, heritable change in the growth
control of cells in culture. No set of characteristics invariably distinguishes
transformed cells from their normal. Transformation to a malignant phenotype is
recognized by tumor formation when transformed cells are injected into appropriate
test animals.
Retroviruses
Retroviruses contain an RNA genome and an RNA-directed DNA
polymerase (reverse transcriptase). RNA tumor viruses in this family
mainly cause tumors of the reticuloendothelial and hematopoietic systems
(leukemias, lymphomas) or of connective tissue (sarcomas).
Important properties of the retroviruses are listed in Table 3
Table 3. Important Properties of Retroviruses.
Virion: Spherical, 80–110 nm in diameter, helical nucleoprotein within
icosahedral capsid
Composition: RNA (2%), protein (about 60%), lipid (about 35%),
carbohydrate (about 3%)
Genome: Single-stranded RNA, linear, positive-sense, 7–11 kb, diploid; may
be defective; may carry oncogene
Proteins: Reverse transcriptase enzyme contained inside virions
Envelope: Present
Replication: Reverse transcriptase makes DNA copy from genomic RNA;
DNA (provirus) integrates into cellular chromosome; provirus is template for
viral RNA
Maturation: Virions bud from plasma membrane
Outstanding characteristics:
Infections do not kill cells
May transduce cellular oncogenes, may activate expression of cell genes
Proviruses remain permanently associated with cells and are frequently not
expressed
Many members are tumor viruses
Tumor Suppressor Genes
Human Retroviruses
The human T-lymphotropic (HTLV) group of retroviruses has probably
existed in humans for thousands of years. HTLV-1 has been established as the
causative agent of adult T cell leukemia-lymphomas (ATL) as well as a
nervous system degenerative disorder called tropical spastic paraparesis. It
does not carry an oncogene. A related human virus, HTLV-2, has been
isolated but has not been conclusively associated with a specific disease.
Transmission of HTLV-1 seems to involve cell-associated virus. Motherto-child transmission via breast feeding is an important mode. Such early-life
infections are associated with the greatest risk of ATL. Blood transfusion is an
effective means of transmission, as are sharing blood-contaminated needles
(drug abusers) and sexual intercourse.
Polyomaviruses
Important properties of polyomaviruses are listed in Table 4.
Table 4. Important Properties of Polyomaviruses.
Virion: Icosahedral, 45 nm in diameter
Composition: DNA (10%), protein (90%)
Genome: Double-stranded DNA, circular, 5 kbp, MW 3 million
Proteins: Three structural proteins; cellular histones condense DNA in
virion
Envelope: None
Replication: Nucleus
Outstanding characteristics:
Stimulate cell DNA synthesis
Viral oncoproteins interact with cellular tumor suppressor proteins
Important model tumor viruses
Human viruses can cause human neurologic and renal disease
May cause human cancer
Papillomaviruses
Important properties of papillomaviruses are listed in Table 5
Table 5. Important Properties of Papillomaviruses.
Virion: Icosahedral, 55 nm in diameter
Composition: DNA (10%), protein (90%)
Genome: Double-stranded DNA, circular, 8 kbp, MW 5 million
Proteins: Two structural proteins; cellular histones condense DNA in virion
Envelope: None
Replication: Nucleus
Outstanding characteristics:
Stimulate cell DNA synthesis
Restricted host range and tissue tropism
Significant cause of human cancer, especially cervical cancer
Viral oncoproteins interact with cellular tumor suppressor proteins
Adenoviruses
The adenoviruses comprise a large group of agents widely distributed in
nature. They are medium-sized, nonenveloped viruses containing a linear
genome of double-stranded DNA (26–45 kbp). Replication is species-specific,
occurring in cells of the natural hosts. Adenoviruses commonly infect humans,
causing mild acute illnesses, mainly of the respiratory and intestinal tracts.