Download - Virus Penyebab CA [Dr. Diana Chusna]
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)