VIRUS PENYEBAB Ca

Diana Chusna Mufida

Pendahuluan

Ca :-merupakan proliferasi sel-sel yang

tidak dapat diatur. -kegagalan deferensiasi -merupakan suatu klon, tidak

menyerang massa sel.

Penyebab Ca

Rangsangan fisis: X-rays Irradiasi uv

Bahan kimia bersifat karsinogenik Siklamat Sakarin Hidrokarbon dalam daging bakar Senyawa klor pada air ledeng

Virus onkogenik,15% penyebab Ca

Virus penyebab Ca

Virus DNA Papovirus : HPV, SV-40, Hepadnavirus : HBV Herpesvirus : EBV,KSHV Adenovirus Poxvirus

Virus RNA Retrovirus : HTLV-1 Flavivirus : hepatitis C virus

Hubungan virus dan malignansi

HPV 16,18,31,33,45 : Ca cervix HBV &HCV : Hepatocelluler Ca HTLV1 : Adult sel T leukemia EBV : Burkitt’s lymphoma Hodgkin,s disease Ca nasopharing KSHV : sarcoma kaposi

Cara virus mengubah sel

Virus yang menginfeksi manusia mengandung gen Ca yang beraktivitas sebagai mutagen

Didukung oleh faktor lain ( genetik, imunologi,lingkungan ) yang diperlukan untuk perkembangan Ca

Sel yang berubah mengandung gen virus dan diekspresikan secara terus menerus

Cara virus mengubah sel

Oncogen virus yang diekspresikan mengubah gen sel yang normal serta mengubah signal transduksi

RNA virus mengaktivasi onkogen DNA virus menekan kerja tumor

supressor

Retrovirus Lifecycle

• LTR-gag-pol-env-LTR

Simple retrovirus

Mekanisme Retrovirus mengubah sel normal menjadi Ca

Retrovirus mentranduksi oncogen Oncogen diaktivasi oleh insersi

retrovirus ( cis-acting/ nontranduksi retrovirus

Oncogen dimediasi oleh protein essensial retrovirus ( trans-activating/ nontransducing long-latency retrovirus )

HTLV-1( Human T sel Leukemia Virus

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

Transmisi

Sexual Transfusi darah Ibu ke anak

Atypical flower pada ATL

HEPATITIS C

a small (50 nm in size), enveloped, single-stranded, RNA virus family Flaviviridae.

Transmisi

Simptom 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)

Diagnosis

Hepatitis virus serology ELISA assay to detect hepatitis C

antibody Hepatitis C PCR test Elevated liver enzymes Liver biopsy shows chronic

inflammation

Terapi

Interferon alpha Ribovirin

DNA TUMOR VIRUS

Beracam-macam grup virus dengan perbedaan struktur, genom dan strategi replikasi

Virus yang menyebabkan Ca: Papilloma EBV,KSHV Hepatitis B

Pada eksperimental : adenovirus, poliomaviorus,SV-40

Herpesvirus

– Large, enveloped DNA viruses – Icosahedral capsids – DNA replicates in the nucleus of host

cells – Cells may become permanently infected – Herpes infections associated with certain cancers – Herpes infections are associated with severe disease in neonates and immunocompromised hosts

Type Name Subfamily Target cell Latency Transmission

1,2 HSV Alphaherpesvirinae mucoepithelia neuron contact 3 VZV Alphaherpesvirinae mucoepithelia neuron contact or respiratory 4 CMV Betaherpesvirinae epithelia monocytes contact monocytes lymphocytes congenital lymphocytes transplantation 5 EBV Gammaherpesvir. B lymphocyte B lymphocyte saliva 6,7 HLV Betaherpesvirinae T lymphocyte T lymphocyte

Respiratory 8 KSHV Gammaherpesvir. Endothelial cells Unknown body

fluids

EBV

Menyebabkan infeksi mononukleosis dengan simptom : Demam Pharingitis exudatif Lymphodenopathy Hepatosplenomegali Atypical lymphocytosis

Komplikasi CNS

Aseptic meningitis Encephalitis Myelitis Optic neuritis Cranial nervi palsy Myelitis GBS

Komplikasi hematologi

Ruptur splen Trombocytopenia Agranulositosis Hemolitic anemia

Diagnosis Lab

Isolasi EBV dari eksudat oropharyng PCR DNA dari serum, plasma dan

jaringan PCR RNA dari sel lymphoid dan

jaringan Serologi :

IgM IgG anti VCA ( viral capsid Ag ) Imunofloresent Ab

leukemia cells that contain Epstein Barr virus

Atypical lymphocyte in a peripheral blood smear

Epstein-Barr virus disease. Bilateral cervical lymphadenopathy

Bilateral cervical lymphodenopathy

Epstein-Barr virus disease with pharyngeal and tonsillar exudate

Rash in a 9-year-old girl with infectious mononucleosis who was

receiving ampicillin

infectious mononucleosis with petechiae on the soft palate and

uvula without exudation.

A conjunctival hemorrhage of the right eye of a patient with infectious

mononucleosis.

Sarkoma Kaposi

Sarkoma Kaposi

neoplasma vaskuler sebagai akibat terjadinya proliferasi dari sel jaringan ikat. KS ditandai dengan timbulnya makula yang berwarna merah ungu atau biru-coklat, plak (plaque) dan nodula pada kulit dan organ tubuh yang lain. Lesi pada kulit jelas, keras atau lembek, soliter atau bergerombol

Disebabkan HHV-8

bentuk secara epidemiologi

. Bentuk KS klasik terjadi pada laki-laki dewasa terutama pada orang Mediterania atau orang Eropa Timur keturunan Yahudi.

Bentuk kedua, bentuk endemis ditemukan di daerah katulistiwa Afrika dan ditemukan pada semua golongan umur.

HPV

Ciri-ciri

Papillomaviruses are small, approximately 52-55nm in diameter. 

They are non-enveloped, icosahedra particles. This shape is made up of 12 pentameric and 60 hexameric capsomers arranged on a T=7 lattice. 

Their carpsid is composed of two proteins, a major (L1) and minor (L2).

HPV They are DNA viruses.  HPV is part of the family known as Papovaviruses,

which was named for it’s three main members: PApillomavirus, POlyomavirus, and simian Vacuolating Agent. They are found in many vertebrates, and exhibit high species specificity.

  This family contains two genera of oncogenic

viruses, Papilloma and Polyoma viruses.

The Papillomavirus’ genome is circular, d/s DNA approximately 8,000bp in size.

How Does HPV Work? HPV infects the basal cells of the dermal layer,

and early gene expression occurs in these cells. 

Late gene expression and high copy DNA synthesis occurs only in terminally differentiated epidermal cells.

This implies a link between differentiation and gene expression, although the nature of this link is unknown.

Some strains of HPV are able to transform host cells on their own, whereas others require cofactors.

HPV Infection OutcomesE6 and E7 interact with many cellular proteins, which influence the

outcome of infection.

A p o p to s is

E 6in te ra c tio n s

b a x

G ro w th A rre s t

E 7in te ra c tio n s

p 2 1

p 5 3

In high-risk HPV strains 16,18,31,39,45 and 59:

Protein E6 interacts with p53 in the host cell and promotes it’s degradation via the ubiquitin dependent pathway.

Protein E7 complexes with retinioblastoma protein (Rb), thereby inactivating it.

Rb and p53 are both tumor suppressors, involved in DNA repair and cell death.

How Does HPV “Cause” Cancer

Faktor resiko

Sexual activity (< 20 years) Multiple sexual partners Exposure to STD Mother or sister with cervical cancer Smoking Immunosuppression

HIV/AIDS Chronic corticosteroid use (asthma and

lupus)