Oncogenic viruses

• An oncovirus is a virus that can cause a benign

or malignant tumour.
• Many DNA and RNA viruses cause tumors in
animals, but in humans it is the DNA viruses
that are implicated in most forms of cancer.
• Only two RNA virus (retroviruses and
Hepatitis C virus) are associated with cancer in
humans
 Oncogenic DNA viruses
Virus Disease
Human papilloma virus Warts, including STD
genital warts
Epstein-Barr virus Infectious mononucleosis
Human herpes virus 8 Kaposi Sarcoma
Hepatitis B virus(HBV) Hepatitis B virus infection
Adenoviruses Acute respiratory disease;
Common cold
Cancer
Uterine (cervical) cancer
Burkitt's lymphoma
Nasopharyngeal carcinoma
Hodgkin's disease
Hepatocellular carcinoma
Adenocarcinomas (cancer
of glandular epithelial
tissues)
Warts
 Oncogenic RNA viruses

• Retroviruses- Human T cell

lymphotrophic virus (HTLV)
• Hepatitis C virus
 Pathogenesis
• Malignant transformation refers to
changes that occur in the growth
properties, shape and in other features of
the tumour cell.
• Malignant transformation can be induced
by tumour viruses not only in animals but
also in cultured cells.
 How do viruses contribute to cancer?

1. The tumour virus may introduce a new

transforming gene (oncogene) into the cell
2. The virus may induce or alter the expression
of pre-existing cellular gene
3. Chronic inflammation( Hepatitis B and C)
 Role of cellular oncogenes in tumour
formation
• A proto-oncogene is a healthy gene found in the cell.
• There are many proto-oncogenes each one is responsible
for making a protein involved in cell growth, division, and
other processes.
• Most of the time, these genes do their jobs without
problems.
• However, if an error (mutation) occurs in a proto-
oncogene, the gene can become turned on when isn’t
supposed to be. If this happens, the proto-oncogene can
turn into a malfunctioning gene called an oncogene. Cells
will start to grow out of control, which leads to cancer.
• Tumour suppressor genes are normal genes
that slow down cell division, repair DNA
mistakes, or tell cells when to die (a process
known as apoptosis or programmed cell death).

• When tumour suppressor genes don't work

properly, cells can grow out of control, which
can lead to cancer
 Human T-cell lymphotrophic virus
• There are two human retroviruses: HTLV and
HIV.
• Human T-cell lymphotrophic viruses contain
two types HTLV-1 and 2.
• Both are associated with leukaemias and
lymphomas.
• The virus is transmitted sexually and from
infected blood.
• HTLV encodes for a protein known as Tax
protein which enhances synthesis of IL-2
(T-cell growth factor) and IL-2 receptor.
• This results in uncontrolled growth of T
cells and malignant transformation.
 Human Papilloma virus
• Is a double stranded DNA virus with an
icosahedral nucleocapsid symmetry.
• Papillomas (warts) are benign but may progress
to form carcinomas especially in
immunocompromised.
• >100 types of HPV.
• Types 16 and 18 are implicated in cervical
carcinoma and anogenital cancers.
• A vaccine is available against HPV 16 and 18
 Human papillomavirus (HPV)
• Family: Papillomaviridae
• Non-enveloped
• Circular, compact double-stranded DNA virus
• > 100 genotypes exist

Oncogenesis

Source Undetermined Source Undetermined

 HPV Infection and Productive Life Cycle

Infectious virions shed

Virus introduced
through microabrasion
Late HPV protein
Virion assembly production
Viral DNA replication L1 & L2

Early HPV protein

production
Virus
E1, E2, E4, E5,
infection
E6, & E7

Serephine, wikimedia commons, Adapted from

Gray’s Anatomy
 HPV Genotypes
Lesion HPV genotype

Cutaneous warts 1, 2, 3, 4, 10

Anogenital warts 6, 11 (responsible for 90% of genital warts)

Low malignancy risk 40, 42, 43, 44, 54, 61, 70, 72, 81

Anogenital warts 16, 18 (responsible for 70% of cervical

High malignancy risk cancers)
26, 31, 33, 35, 39, 45, 51, many others
D. Miller
• Transmission
– Direct skin-skin and skin-fomite contact

• Symptoms
– Frequently asymptomatic
– Cutaneous changes occur slowly
– Flat, slightly elevated appearance

• Complications Source Undetermined

– Malignancy
• Increased risk with
immunosuppression
– Respiratory papillomatosis (infants)
– Epidermodysplasia verruciformis (is a
genetic dermatologic condition )

Source Undetermined
 Carcinogenesis in HPV
• HPV encodes two genes called E6 ad E7.
• These two genes interfere with the activity of
two proteins that are encoded by two
suppressor genes p53 and Rb (retinoblastoma)
found in normal cells.
 HPV Treatment and Prevention
• Treatment
– Ablative therapy most often used
• Cytotherapy, surgical excision

• Prevention
– Subunit vaccine
– L1 “virus-like particles” (VLPs) produced in yeast
– Two FDA-approved versions
• Gardasil (Merck), approved June 2006, quadrivalent (HPV 6, 11, 16, and
18)
• Cervarix (GlaxoSmithKline), approved October 2009, bivalent (HPV 16
and 18)
HPV vaccine mimics the infectious virion

Non-Infectious HPV Vaccine

Infectious HPV
(VLP) (virus like particles)

– Capsid protein L1 – Capsid protein L1

– L2 protein – Lacks L2 protein
– Viral DNA – Lacks viral DNA
 HPV Vaccine Recommendations
• Target group (currently)
– Females 9 to 26 years old
– Recommended age 11-12 years old (can be used as young as 9 yo)
– “Catch up” vaccination for 13-26 year old females
• No screening (HPV DNA or antibody) needed
– Immunosuppressed and lactating females NOT disqualified
– Booster requirements not yet known

• Contraindications
– Hypersensitivity to yeast
– Pregnancy (relative)

• Future targets (studies ongoing)

– Females >26 years old
– Males
 Polyomaviruses and cancer

• Family: Polyomaviridae (formerly grouped with papillomaviruses)

• Non-enveloped, closed circular double-stranded DNA genomes

• Examples
– BK virus (BKV) (BK abbreviation of the name of the first patient)
• Hemorrhagic cystitis and polyomavirus nephropathy
– JC virus (JCV)
• Progressive multifocal leukoencephalopathy (PML)
– Simian virus 40 (SV40) (found in both monkeys and huma
– Merkel cell virus (MCV)
 EBV
• Is a herpesvirus that causes infectious
mononucleosis.
• The exact mechanism by which EBV may causes
malignancies is not well understood,
• Cells from individuals with Burkitt’s lymphoma
(cancer of the lymphatic system) were found to
contain EBV DNA.
• It is also associated with nasopharyngeal
carcinomas and Hodgkin’s lymphoma (cancer of the
lymphatic system)
 Burkitt’s lymphoma
• The exact mechanism by which EBV may cause
Burkitt’s lymphoma is not well understood.
• Hypothesis is that EBV infection induces B cells
to proliferate.
• When cells proliferate this increases the
likelihood that a second event such activation
of a cellular oncogene will occur.
• In Burkitt’s lymphoma a cellular oncogene
called c-myc which is normally located in
chromosome 8 becomes translocated to
chromosome 14 at the site of heavy chain
genes
• EBV antibodies are produced in excess and if
an oncogene happens to be placed next to a
gene for antibody production, then oncogenes
will also be produced in excess.
Burkitt’s lymphoma
 HBV
• Hepatitis B is significantly more common in
patients with hepatocellular carcinoma
• Therefore hepatocellular carcinoma is more
common in areas of Africa and Asia where the
incidence of HBV is higher.
• Chronic hepatitis B infection predisposes to
hepatocellular carcinoma as a result of
persistent cellular regeneration that attempts to
replace dead hepatocytes
 HBV cont.’d
• Part of the HBV genome is integrated into
cellular DNA in malignant cells.
• But no HBV gene has been definitely
implicated in oncogenesis
• The insertion of HBV DNA may cause
insertional mutagenesis which results in the
activation of a cellular oncogene
 HCV
• Chronic HCV, like HBV also predisposes to
hepatocellular carcinoma.
• HCV is an RNA virus that has no oncogene.
• It causes chronic hepatitis which is the main
predisposing factor for the formation of
hepatocellular carcinoma.
Source Undetermined

Source Undetermined
 HHV-8
• Human herpes virus 8 is a DNA virus that
belongs to the herpesviridae.
• HHV-8 causes Kaposi sarcoma.
• HHV-8 causes malignant transformation by
inactivation of a tumour suppressor gene.
KS Clinical Manifestation
 Red, purple, brown, or black papular
nodules
 Skin, mouth, lung, and GI tract Varied
growth rate (indolent to aggressive)

Pathology
 Malignancy of lymphatic endothelium
that forms vascular channels
Kaposi sarcoma