Oncogenic Viruses

Dini Agustina

{
Mikrobiologi FKUJ
Basic virology
Characteristic and Structure

{ General concept
Classification
 A noncellular organism
Having genetic nucleic acid that requires a host to replicate.

15 to 450 nanometers (nm) in diameter.

Do not have a cell membrane or cell wall

Have a rigid protein coat called the capsid.

The inner cavity contains DNA or RNA.

Viruses come in various shapes .

One end is usually broader (head), and one end narrower (tail).

The tail often has antigenic proteins for attachment to the host

Characteristic
 {
A schematic depicting how different viruses compare in size
to other microorganisms, such as a single bacterium (blue)
and human hepatocyte (tan).

Virus size
BASIC STRUCTURAL FORMS OF VIRUSES
Bacteriophages
a virus that infects and replicates within a bacterium
Levinson W, Jawetz E: Medical Microbiology & Immunology Examination & Board Review, 6th ed. McGraw-Hill, 2000. Modified there
from Jawetz E, Melnick JL, Adelberg EA: Review of Medical Microbiology, 16th ed. McGraw-Hill, 1984
 viruses require a host cell to replicate and spread
to other adjacent cells as they do not possess the
ability to reproduce on their own completely
dependent on the cellular metabolism of the host
for reproductionas obligate intracellular
parasites.
So what virus mode infection and How

mechanism of immunity to viruses ?

General concept
Virus mode of infection. (A) Viral-envelope antigens bind to receptors on the host cell and is
taken up. (B) Viral proteins are expressed and presented by MHC class I molecules by the infected
cell. At this point, the infected cell is a target for cytotoxic T lymphocytes (CTL). (C) Viral effects on
host cell surface proteins; target for CTL or natural killer cells. (D) Viral proteins inserted into host
cell membrane; antibodies bind, causing cell death by antibody-dependent cell-mediated
cytotoxicity (ADCC) or by complement fixation (not shown).
Examples of antibody-mediated mechanisms against viral infections. Opsonization is
effective against both enveloped (A) & non-enveloped viruses (B). Enveloped viruses are also
susceptible to direct complement-lysis by membrane attack complex (MAC)
Oncogenic viruses
{ DNA tumor viruses
RNA tumor viruses
 1.Oncogenes
(+)
2. Tumor-
suppressor
genes (-)

Tumor
1. Stimulatory for growth and which cause 2. Inhibit cell growth and which cause
cancer when hyperactive cancer when they are turned off
 Salah satu pemicu terjadinya kanker.
Dapat menyebabkan perubahan-perubahan yang
mempengaruhi proses onkogenesis.
Saat menginfeksi sel dapat menyebabkan mutasi proto-
onkogen sel menjadi onkogen.
RNA virus mengaktivasi onkogen
DNA virus menekan kerja tumor supressor
 Papovaviridae : HPV, SV-40,
Hepadnaviridae : HBV

Herpesviridae : EBV,KSHV

Adenoviridae

Poxviridae

DNA Tumor Viruses

 HPV 16,18,31,33,45 : Ca cervix
HBV &HCV : Hepatocelluler Ca
HTLV1 : Adult sel T leukemia
EBV : Burkitts lymphoma
Hodgkin,s disease
Ca nasopharing
KSHV : sarcoma kaposi

Hubungan virus dan

malignansi
 Small (52-55nm) non-enveloped icosahedral DNA
virusesThis shape is made up of 12 pentameric and 60
hexameric capsomers arranged on a T=7 lattice.
The major capsid protein, L1, minor capsid protein, L2 or L3

Genome size about 8 kilobases

These viruses cause warts and also human and animal

cancers. Warts are usually benign but can convert to

malignant carcinomas.
There are more than 100 types but, clearly, not all are

associated with cancers; however, papillomas may cause

16% of female cancers worldwide and 10% of all cancers.
 HERPESVIRUS

Herpesviruses are much larger than the DNA viruses described

above
Genome size of 100 to 200 kilobases.
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 have over 100 genes.
 Epstein-Barr virus (Human herpes virus 4)

EBV is the herpes virus that is most strongly associated with

cancer.
Infects primarily lymphocytes and epithelial cells. In
lymphocytesnon-productive infection, epithelial cells
productive infection.
EBV is causally associated with:
a. Burkitt's lymphoma common in malaria-endemic regions
b. Nasopharyngeal cancer, particularly in China and SE Asia,
where certain diets may act as co-carcinogens
c. B cell lymphomas in immune suppressed individuals (such as
in organ transplantation or HIV)
d. Hodgkin's lymphoma in which it has been detected in a high
percentage of cases (about 40% of affected patients)
e. X-linked lymphoproliferative Disease (Duncan's syndrome)
 EBV also causes infectious mononucleosis
(glandular fever). This is a self-resolving infection
of B-lymphocytes which proliferate benignly.
Often infection goes unnoticed (it is sub-clinical)
About half of the population in western countries
has been infected
Reach 20 years of age.
Symptoms : fever, sore throat, rash, swolen lymph
node, fatique
 Human Herpes Virus 8 (HHV-8, Kaposi's Sarcoma
Herpes Virus)
HHV-8 infects lymphocytes and epithelial/endothelial
cells
Causative agent of Kaposi's sarcoma.
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.
EBV and HHV-8 have been found to be associated with
oral lesions and neoplasms in HIV-infected patients.
Oral hairy leukoplakia (OHL)benign and causes white
thickenings on the tongue epithelium in which these
viruses proliferate.
Four clinically relevant and different types of KS have been
identified:

1. Classical or sporadic KS, originally described as an indolent

tumor in the extremities of elderly males of eastern and
Mediterranean Europe.
2. Endemic KS, predominant in eastern and central sub-
Saharan Africa before the AIDS epidemic and clinically
similar to Classical KS, but also seen in a more fulminant
and fatal form in children.
3. AIDS associated KS, the most frequent tumor of HIV-I
infection and the most aggressive and rapidly growing form
of KS, with early dissemination to the skin and viscera.
4. Iatrogenic KS, seen in drug related immunosuppressed
patients, e.g. transplant patients.
HEPATITIS B VIRUS
Hepatitis B virus is a DNA virus, but much more similar to the
oncornaviruses (RNA tumor viruses) in its mode of replication reverse
transcription.
Hepatitis B is a vast public health problem hepatocellular carcinoma
(HCC)
There is a very strong correlation between HBsAg (hepatitis B virus
surface antigen) chronic carriers and the incidence of HCC.
In Taiwan, it has been shown that HBsAg carriers have a risk of HCC
that is 217 times that of a non-carrier. 51% of deaths of HBsAg carriers
are caused by liver cirrhosis or HCC compared to 2% of the general
population.
Paramasivan Piramanayagam, Gourdas Choudhuri. 2007. Hepatitis B: News from the
research world. Hepatitis B annual. Volume 4 | Issue 1 DOI:10.4103/0972-9747.45094
Farazi and DePinho Nature Reviews Cancer 6, 674687 (September 2006) | doi:10.1038/nrc1934
 Retrovirus : HTLV-1
Flavivirus : hepatitis
C virus

RNA Tumor Viruses

Retrovirus Lifecycle
 Retrovirus mentranduksi oncogen
Oncogen diaktivasi oleh insersi

retrovirus ( cis-acting/ nontranduksi

retrovirus
Oncogen dimediasi oleh protein essensial

retrovirus ( trans-activating/
nontransducing long-latency retrovirus )

Mekanisme Retrovirus mengubah

sel normal menjadi Ca
 Berhubungan dengan 2 penyakit yang fatal
pada manusia , yaitu :
Adult T cell lekemia ( ATL )

Tropical spastic para paresis/ HTLV-1 yang

berhubungan dengan myelopathy
Endemic di Jepang, USA, Africa dan Karabia

Infeksi asimptomatik, 2-5% , 20-40 tahun

berkembang menjadi keganasan

Menginfeksi CD4+ Tsel

HTLV-1
( Human T sel Leukemia Virus )
Masao Matsuoka. 2003. Human T-cell leukemia virus type I and adult T-cell leukemia
Oncogene. 22, 51315140. doi:10.1038/sj.onc.1206551
Atypical flower pada ATL
 a small (50 nm in size),
enveloped,

single-stranded,

RNA virus

family Flaviviridae.

HEPATITIS C
Transmisi
 Jaundice
Abdominal pain (right upper abdomen)

Fatigue
Loss of appetite

Nausea

Vomiting

Low-grade fever

Pale or clay-colored stools

Dark urine

Generalized itching
Ascites

Bleeding varices (dilated veins in the

esophagus)

Symptom
Ahuja et al., 2014. Human oncogenic viruses and
cancer. CURRENT SCIENCE, VOL. 107, NO. 5
Referensi
1. Hunt M. 2014. BASIC VIROLOGY: DEFINITIONS, CLASSIFICATION,
MORPHOLOGY AND CHEMISTRY. Microbiology and Immunology Online.

2. Ahuja R, et al., 2014. Human oncogenic viruses and cancer. CURRENT

SCIENCE. VOL. 107, NO. 5

3.The Pathogen Profile Dictionary. J. Ugrad. Biol. S. 2010

4. Toy, et al. 2008. Case Files Microbiology 2ed. Mc Graw Hill Lange. New York

5. Brooks et al., 2007. Jawetz, Melnick and adelbergs Medical Microbiology 24ed.
Mc Graw Hill. New York