Oncogenic Viruses
Professor Sudheer Kher
What’s that?
An oncovirus is a associated with .
Oncoviruses come in two different forms: viruses with a
, such as , and viruses with an
RNA genome, like the Human viruses and
several viruses known to be common in cats, mice and
chickens.
Types of tumor viruses
DNA 1- Papovavirus (papilloma)
Viruses 2- Herpes viruses ( HSV-2 & EBV)
3- Hepatitis B virus
4- Pox virus (molluscum contagiosum)
5- JC virus
1- Retrovirus family: HTLV-1 RNA
2- Flavivirus: HCV Viruses
How important?
Experimental and epidemiological data imply a causative role
for viruses and they appear to be the second most important
risk factor for cancer development in humans, exceeded only
by tobacco usage.
Mechanism
The oncogenic mechanism is either to insert additional
oncogenic genes in the host DNA, or to enhance already
existing oncogenic genes in the genome.
Mechanisms of cell transformation
All tumor viruses are either DNA or RNA viruses that generate
DNA provirus after being integrated into the host cell
chromosome
Integrated viral genes can use host cell transformation through:
1- Introduction of a new transforming gene into the cell called viral
oncogene ( v onc)
2- Alteration of expression of a cellular [Link] can
result from insertional mutation, translocation, or gene
amplification
3- Viral proteins may inactivate a tumor suppressor gene as p53
tumor suppressor gene that is altered in 50% of human cancers
The mode of virally-induced tumors
Acutely-transforming - In acutely transforming viruses, the viral
particles carry a gene that encodes for an overactive oncogene
called viral-oncogene (v-onc), and the infected cell is transformed
as soon as v-onc is expressed.
Slowly-transforming - In contrast, in slowly-transforming viruses,
the virus genome is inserted, especially as viral genome insertion is
an obligatory part of retroviruses, near a proto-oncogene in the
host genome. The viral promoter or other transcription regulation
elements in turn cause overexpression of that proto-oncogene,
which in turn induces uncontrolled cellular proliferation. Because
viral genome insertion is not specific to proto-oncogenes and the
chance of insertion near that proto-oncogene is low, slowly-
transforming viruses have very long tumor latency compared to
acutely-transforming viruses, which already carry the viral
oncogene.
Virus – Cancer link
DNA viruses
JC virus has been found in malignant colon tumors and may be linked to colon cancer.
Human Papilloma Virus (HPV), a DNA virus, causes transformation in cells through
interfering with tumor suppressor proteins such as p53. Interfering with the action of
p53 allows a cell infected with the virus to move into a different stage of the cell cycle
allowing the virus genome to be replicated forcing the cell into the S phase of the cell
cycle could cause the cell to become transformed. It increases risk of e.g. cervical cancer.
Human herpes virus 8 is associated with Kaposi’s sarcoma, a type of skin cancer.
Epstein Barr Virus (EBV) is associated with four types of cancers
RNA viruses
It is not only DNA viruses that are associated with cancers some RNA viruses have also
been associated such as the Hepatitis C Virus as well as Human T cell leukaemia virus-1
(HTLV-1)
Important cancers of viral origin
Hepatitis viruses, including Hepatocellular carcinoma
hepatitis B and hepatitis C
Human T-Lymphotropic virus T cell leukemia
Human papilloma viruses Cancers of cervix skin, penis,
anus.
Kaposi’s sarcoma-associated Kaposi’s sarcoma
herpesvirus Body cavity lymphoma
Epstein-Barr virus Burkitt’s lymphoma
Nasopharyngeal carcinoma
Hodgkin’s lymphoma
B lymphoproliferative disease
Different tumors produced by DNA oncogenic viruses
Different tumors produced by RNA
oncogenic viruses
Hepatitis viruses & Hepatocellular
carcinoma
Hepatitis B and hepatitis C, can induce a chronic viral infection
that leads to liver cancer in 0.47% of hepatitis B patients per year
(especially in Asia, less so in North America), and in 1.4% of
hepatitis C carriers per year.
Liver cirrhosis, whether from chronic viral hepatitis infection or
alcoholism, is associated with the development of liver cancer, and
the combination of cirrhosis and viral hepatitis presents the highest
risk of liver cancer development. Worldwide, liver cancer is one of
the most common, and most deadly, cancers due to a huge burden
of viral hepatitis transmission and disease.
Vaccine for cancer prevention
Advances in cancer research have made a vaccine designed to
prevent cancer available.
In 2006, the US FDA approved a human papilloma virus vaccine,
called Gardasil. The vaccine protects against four HPV types,
which together cause 70% of cervical cancers and 90% of genital
warts.
In March 2007, the US CDC Advisory Committee on
Immunization Practices (ACIP) officially recommended that
females aged 11-12 receive the vaccine, and indicated that females
as young as age 9 and as old as age 26 are also candidates for
immunization.
