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Presented by: Sameen Noushad

Dated: 18-April-2014
Role of Viruses in
Cancer
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Table of Contents
INTRODUCTION ............................................................................................................................................. 3
MECHANISM ................................................................................................................................................. 3
CLASSES OF TUMOR VIRUSES ....................................................................................................................... 3
DNA TUMOR VIRUSES ............................................................................................................................... 4
FAMILY: PAPOVAVIRIDAE - PAPOVAVIRUSES ....................................................................................... 4
COMPLEX TUMOR VIRUSES ...................................................................................................................... 6
FAMILY: HERPESVIRIDAE ....................................................................................................................... 6
FAMILY: HEPADNAVIRIDAE ................................................................................................................... 8
RNA TUMOR VIRUSES (RETROVIRUSES).................................................................................................... 9
ONCOVIRINAE ....................................................................................................................................... 9
FLAVIVIRIDAE FAMILY ......................................................................................................................... 10
REFERENCES: ............................................................................................................................................... 11



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INTRODUCTION
Cancers are the result of a disruption of the normal restraints on cellular proliferation.
There are two classes of these genes in which altered expression can lead to loss of
growth control:

(a) Those genes that are stimulatory for growth and which cause cancer when
hyperactive. Mutations in these genes will be dominant. These genes are called
oncogenes.
(b) Those genes that inhibit cell growth and which cause cancer when they are turned
off. Mutations in these genes will be recessive. These are the anti-oncogenes or tumor-
suppressor genes.
Viruses are involved in cancers because they can either carry a copy of one of these
genes or can alter expression of the cell's copy of one of these genes.
MECHANISM
There are two types of cancers caused by viruses: acutely transforming or slowly
transforming cancers. In acutely transforming viruses, the virus carries an overactive
oncogene, and the infected cell becomes cancerous as soon as the overactive viral
gene is expressed. In contrast, in slowly transforming viruses, the virus genome is
inserted near a previously existing proto-oncogene in the genome of the infected cell.
The virus causes overexpression of that proto-oncogene, which typically induces
uncontrolled cell division. Because the virus' genes might not insert near enough to a
proto-oncogene to trigger the cancerous changes, and, even if optimally located, it
might take some time to become activated, slowly transforming viruses usually cause
tumors much longer after infection than the acutely transforming viruses, if at all.
CLASSES OF TUMOR VIRUSES
There are two classes of tumor viruses:

DNA tumor viruses RNA tumor viruses
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DNA TUMOR VIRUSES
DNA tumor viruses have two life-styles:
In permissive cells, all parts of the viral genome are expressed. This leads to viral
replication, cell lysis and cell death
In cells that are non-permissive for replication, viral DNA
is usually, but not always, integrated into the cell
chromosomes at random sites. Only part of the viral
genome is expressed. This is the early, control functions
(e.g. T antigens) of the virus. Viral structural proteins are
not made and no progeny virus is released.
FAMILY: PAPOVAVIRIDAE - PAPOVAVIRUSES
The papovaviridae are small non-enveloped icosahedral
DNA viruses. The major capsid protein, VP1, is present
as 72 pentamers. Each pentamer is associated with one
molecule of another minor capsid protein, either VP2 or
VP3. The DNA is complexed with histone proteins
encoded by the host cell.
PAPILLOMAVIRUSES
1. Papilloma viruses have a genome size about 8
Fig. 1 Epidermodysplasia
verruciformis
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kilobases. They cause warts and also human and animal cancers. Warts are
usually benign but can convert to malignant carcinomas. This occurs in patients
with epidermodysplasia verruciformis.
2. EPIDERMODYSPLASIA VERRUCIFORMIS is also known as Lewandowsky-
Lutz dysplasia or Lutz-Lewandowsky epidermodysplasia verruciformis and is
very rare. It is an autosomal recessive mutation that leads to abnormal,
uncontrolled papilloma virus replication. This results in the growth of scaly
macules and papules on many parts of the body but especially on the hands and
feet. See figure 1.

3. Epidermodysplasia verruciformis, which is
associated with a high risk of SKIN CARCINOMA,
is typically associated with HPV types 5 and 8 (but
other types may also be involved). These infect
most people (up to 80% of the population) and are
usually asymptomatic. See figure 2.

4. Papilloma viruses are also found associated with human penile, uterine, cervical
and anal carcinomas and are very likely to be their cause; moreover, genital
warts can convert to carcinomas. HPV also has been linked to cancer of the
vagina (the birth canal) and, to a lesser
extent, cancer of the vulva (the
external part of a womans genitalia,
including the labia).

5. SQUAMOUS CELL CARCINOMAS
OF LARYNX, ESOPHAGUS AND
LUNG appear very like cervical
carcinoma histologically and these may
also involve papilloma viruses.

6. Recently, a strong causal link between certain ORAL-PHARYNGEAL
CANCERS and HPV16 has been demontsrated. See figure 3.
There are more than 100 types of human papilloma viruses but, clearly, not all are
associated with cancers; however, papillomas may cause 16% of female cancers
worldwide and 10% of all cancers.

Fig.2 Skin Carcinoma
Fig.3 Oral cancer
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COMPLEX TUMOR VIRUSES
FAMILY: HERPESVIRIDAE
HERPESVIRUSES
Herpesviruses are much larger than the DNA viruses described above and have a
genome size of 100 to 200 kilobases. Because of their large size, a lot remains to be
discovered concerning the way in which these viruses transform cells.
There is considerable circumstantial evidence that implicates these large enveloped
viruses in human cancers and they are highly tumorigenic in animals. The herpes virus
genome integrates into the host cell at specific sites and may cause chromosomal
breakage or other damage. Herpesviruses are often co-carcinogens. They may have a
hit and run mechanism of oncogenesis, perhaps by expressing proteins early in
infection that lead to chromosomal breakage or other damage.
Epstein-Barr virus (Human herpes virus 4)
1. EBV is the herpes virus that is most strongly associated with cancer. It infects
primarily lymphocytes and epithelial cells. In lymphocytes, the infection is usually
non-productive, while virus is shed (productive infection) from infected epithelial
cells.
EBV is causally associated with: See figure 4.

BURKITT'S
LYMPHOMA in
the tropics,
where it is
more common
in malaria-
endemic
regions
HODGKIN'S
LYMPHOMA in
which it has
been detected
in a high
percentage of
cases (about
40% of affected
patients)
X-linked
lymphoprolifer
ative Disease
(DUNCAN'S
SYNDROME)
NASOPHARYN
GEAL CANCER,
particularly in
China and SE
Asia, where
certain diets
may act as co-
carcinogens
Fig.4 EBV diseases
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2. EBV also causes infectious mononucleosis, otherwise known as glandular fever.
This is a self-resolving infection of B-lymphocytes which proliferate benignly.
Often infection goes unnoticed (it is sub-clinical) and about half of the population
in western countries has been infected by the time they reach 20 years of age.
Why this virus causes a benign disease in some populations but malignant
disease in others is unknown.

Human Herpes Virus 8 (HHV-8,
Kaposi's Sarcoma Herpes Virus)
3. HHV-8 infects lymphocytes
and epithelial/endothelial cells and
is the causative agent of
KAPOSI'S SARCOMA. See figure
5. It has also been associated
with hematologic malignancies,
including primary effusion
lymphoma, multicentric CASTLEMAN'S (also Castelman's) disease (MCD),
MCD-related immunoblastic/plasmablastic lymphoma and various atypical
lymphoproliferative disorders.

4. EBV and HHV-8 have been found
to be associated with oral lesions
and neoplasms in HIV-infected
patients. Among these diseases is
ORAL HAIRY LEUKOPLAKIA
(OHL) which is benign and causes
white thickenings on the tongue
epithelium in which these viruses
proliferate. See figure 6.

Human cytomegalovirus (Human Herpes
Virus 5)
5. This herpes virus is frequently
associated with Kaposi's sarcoma but this disease is now thought probably to
be caused by human herpes virus 8.

Fig.5 Kaposis Carcinoma
Fig.6 Oral hairy leukoplakia
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FAMILY: HEPADNAVIRIDAE
HEPATITIS B VIRUS
1. Hepatitis B virus
is very different
from the other
DNA tumor
viruses. Indeed,
even though it is
a DNA virus, it is
much more
similar to the
oncornaviruses
(RNA tumor viruses) in its mode of replication.
Hepatitis B is a vast public health problem and HEPATOCELLULAR CARCINOMA
(HCC), which is one of world's most common cancers, may well be caused by HBV.
See figure 7.












Fig. 7 HCC
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RNA TUMOR VIRUSES (RETROVIRUSES)
Retroviruses are different from DNA tumor viruses in that their genome is RNA but they
are similar to many DNA tumor viruses in that the genome is integrated into host
genome.
Since RNA makes up the
genome of the mature
virus particle, it must be
copied to DNA prior to
integration into the host
cell chromosome. This life
style goes against the
central dogma of
molecular biology in
which that DNA is copied
into RNA.GROUPS OF
RETROVIRUSES
ONCOVIRINAE

These are the tumor viruses and those with similar morphology. The first member of
this group to be discovered was Rous Sarcoma Virus (RSV) - which causes a slow
neoplasm in chickens.
Viruses in this group that cause tumors in humans are:
1. HTLV-1 (human T-cell lymphotropic virus-1) which causes ADULT T-CELL
LEUKEMIA (SEZARY T-CELL LEUKEMIA). This disease is found in some
Japanese islands, the Caribbean, Latin America and Africa. HTLV-1 is
sexually transmitted See figure 8.

2. HTLV-2 (human T-cell
lymphotropic virus-2) which causes
HAIRY CELL LEUKEMIA. The virus
is endemic to very specific regions of
the Americas, particularly in native
American populations. See figure
9.

Fig. 8 Adult T- cell leukemia
Fig 9. Hairy Cell Leukemia
Fig 8. Adult T-Cell Leukemia
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FLAVIVIRIDAE FAMILY
3. Until recently the only RNA tumour viruses belonged to the family
Retroviridae. Now it seems that a member of the Flaviviridae family can also
cause tumours.
Hepatitis C virus was
identified in 1989 as the
cause on 90% of non-A
non- B hepatitis
infections. It is an
enveloped virus and
contains a single
stranded RNA genome
of 9.5kb. The virus is
undoubtedly transmitted
by blood contact.
Perinatal and sexual
transmission may also
occur. Infection may be
asymptomatic for
decades but the majority
of infections eventually
result in hepatitis and
hepatocellular
carcinoma. Conditions
for growth in vitro have
not yet been established and little is known about the pathology and cancer
caused by the virus. See figure 10.

4. A retrovirus called XMRV (xenotropic murine leukemia virus-relatedvirus) was
detectedin 40% of prostate tumors from men who werehomozygous for an
allelic variant of the RNASEL gene and in only 2% of tumors from men of
other genotypes. The gene codes for RNase L, a ribonuclease required for
the response to interferon. Activity is impaired in the allelic variant.Activity is
impaired in the allelic variant.



Fig 10. Liver affected with cancer
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REFERENCES:

http://pathmicro.med.sc.edu/lecture/retro.htm
http://njms.rutgers.edu/gsbs/olc/molonc/prot/2012/MolOncolVirus2012BW.pdf
http://www.mcb.uct.ac.za/cann/335/Trans2.html
http://en.wikipedia.org/wiki/Infectious_causes_of_cancer#Viruses
http://www.slideshare.net/manashkpaul/virus-and-cancer