Viral Oncogenesis

ALVAREZ CARLOS JOSE; LUNA YURLEY ANDREA; PREZ RIVAS CARLOS

Source:(Dimmock, et al., 2016)

Content
Presentation
History
Conceptualization
Pathway Activation oncogenic
Oncogenic activation
Virus associated with cancers and tumors
Characteristics of some viral families
Oncogenic viruses affecting mammals
The sine quanon condition
HPV, viral mechanisms and detection techniques
History viruses and cancer
History viruses and cancer
Conceptualization
 Cellular oncogenes are oncogenes that use specific sequence elements
only to encode a transforming protein. Viral Oncogenes are hybrids that
use essential viral RNA sequences (eg gag) and specific to encode
transforming proteins.

They often lose sequences at both ends, they have no introns present, viral
oncogenes are a mutated form of cellular oncogenes
How do genes alter its expression?

Oncogenes: These genes are stimulatory for growth and cause cancer when
hyperactive. Mutations in these genes will be dominant.

Tumor suppressor genes or anti-oncogenes: These genes inhibit cell growth

and cause cancer when they are turned off. Mutations in these genes will be
recessive.
Pathway Activation oncogenic

Source Mesri, et al. (2014)

Activation

Fig. Effect on cellular genes of Retrovirus insertion.

P53: The guardian of the genome

Controlling cellular responses to various cellular

stresses, including DNA damage, aberrant Apoptosis
oncogene activation, loss of normal cellcell
contacts, nutrient deprivation, and abnormal
reactive oxygen species (ROS) production.
Cellular
proliferation
Following cellular stresses, p53 is activated and
primarily functions as a transcriptional regulator of
expression of multiple effector proteins and
miRNAs, which, in turn, regulate key cellular Autophagy
processes such

Source Zaica, et al.(2015)

P53 pathway

Source: Cell Cycle (2005)

Hyperplasia: increase in the number of cells
(dividing faster than normal) of a tissue in a
specific area. The result is increased organ
size such as benign prostatic hyperplasia or
the appearance of a benign nodule.
Neoplasia is the ability to form a tumor, that
is, any uncontrolled growth of abnormal
cells or tissues in the body. The neoplasm
can be benign or malignant.

Source: Web
 p53-ARF
pRb/ARF
RB
Table (Diaposita 8)

Capture
Insertion of genes

Source: Adapted (Dimmock, et al., 2016)

Adenoviruses, polyomaviruses,
papillomaviruses
Also have completely different disease
profiles:

Source: Web

The mechanisms by which these viruses can immortalize and transform

appropriate cells in culture should be so similar.

- A) Adenovirus, SV40 and polyomavirus

- B) Bovine papillomavirus type 1 (BPV1)

Source: Web
Source: Dimmock, et al., 2016

Source: Dimmock, et al., 2016

Polyomaviruses and human cancer
Merkel cell polyomavirus
Merkel cells are mechano sensory cells in the skin, Merkel cell
carcinomas occur relatively rarely.

MCPyV/2008

Source: Web
Herpesvirus involvement in human
cancers
Epstein-Barr virus Human herpesvirus 8
Is the most recently recognized
human herpesvirus.

Source: Web

Source: Web
Retroviruses as experimental model
tumour viruses
Adult T cell leukaemia in Tumour of CD4+ T
humans (HTLV-1) lymphocytes.
The first human retrovirus
1980.

Source: Web Source: Web

Hepatitis viruses and liver cancer
Infection by hepatitis B virus (HBV)
may either be resolved by the
immune response or become
frequent in people infected in
infancy. Those who become
chronically infected have a 200 Source: Web
fold increased risk of developing
primary.

As the HBV X protein can both

transactivate transcription and
disrupt p53 function.

Source: Web
This inactivates the integrated
virus but can gives the host cell
a replicative advantage
sometimes leading to
hepatocarcinoma.
"The sine quanon condition for a virus to cause a tumor is that it is
not lithic."
The virus under this condition must remain latent and produce a chronic
disease.

Source: Authors
Oncolytic viruses can target oncogenic
pathways.

Source: Howard L., et al. (2015)

 VPH

Fig. A: Human papilloma virus particles. B: Schematic Fig. Non-enveloped. Small, icosahedral, about 60
representation of the HPV genome 16 (Picconi 2013). nm in size. A single molecule of circular dsDNA is
contained within the T=7 icosahedral capsid,
which is composed of 72 pentamers (ViralZone).
Induction of cervical cancer induced by the
Human Papilloma Virus.
Induction of cervical cancer induced by the
Human Papilloma Virus.

Fig. Induction of cervical cancer by HPV (Annika Rhl 2008).

 Induction of cervical cancer induced by the
Human Papilloma Virus.
E1/E2: E6 and E7
E6: p53
E7: pRb-E2F; p33 - E7+p21cip1= Koilocyte
L1/L2
LCR: E6 Telomerase M2

Fig. Cell division phases (Web).

Fig. HPV-mediated progression to cervical cancer (Woodman, Collins, and Young 2007).
Mechanisms of detection in laboratory of viral
oncogenes.
Table. Oncogenes identification
methods (Kufe et al., 2003).

Immunohistochemistry (Brouchet et al., 2005)

- DNA amplification.
- Chromosomal translocation.
- Viral homolog.
- Mutagenesis of insertion.
- DNA transfection.
- DNA sequence.
- Proviral insertion.
- Point mutation (Kufe et al., 2003).
Mechanisms of detection in laboratory of viral
oncogenes.
Table . Commercial systems for the detection of HPV in the clinical practice most used worldwide (Picconi 2013).
Mechanisms of detection in laboratory of viral
oncogenes.

Fig. Detection of HPV DNA by capture of hybrids (Picconi 2013).

Mechanisms of detection in laboratory of viral
oncogenes.

Fig. Detection of HPV by PCR (Melo et al., 2005).

Mechanisms of detection in laboratory of viral
oncogenes.

PCR-Real Time Gen Viral L1

Fig. Detection of HPV DNA using the Cobas 4800 system (Picconi 2013).
Mechanisms of detection in laboratory of viral
oncogenes.

Fig. Detection of messenger RNA from the oncogenes E6 and E7 of HPV-AR (Picconi 2013).