Ridho

Islamie, S.Farm., M.Si., Apt.

Faculty of Pharmacy
University of Surabaya
2015

MIKROBIOLOGI FARMASI (11.4466)

Virus onkogenik
Virus penyebab kanker (10% induksi virus)
Virus DNA onkogenik:
HSV-1 Kanker bibir & mulut,
HSV-2 & HPV Serviks
EBV Kanker limfoma BurkiI,
HBV Kanker haK/liver

Virus RNA onkogenik Retroviridae:

HTLV-1 & 2 (Retrovirus leukimia sel T & limfoma)

CIRI KHAS VIRUS ONKOGENIK

Material geneRk + DNA sel inang ! Integrated
Replikasi ! kromosom sel inang
Mengubah karakterisRk sel inang

Prion
A prion is a small infecKous parKcle that
contains a protein without nucleic acids
Protein infeksius Nervous system
Scrapie Domba
Mad cow disease Penyakit sapi gila
The gene for PrPC is located on chromosome
20 in humans
Recent evidence suggests that PrPC is
involved in regulaKng cell death

How protein can be

infecRous?

Conversion of a normal host

glycoprotein called PrPC (for cellular
prion protein) into an infecRous form
called PrPSc (for scrapie protein).

Viroid
InfecKous RNA molecules

Circular small

Tomato
Single-stranded RNA molecules
the smallest pathogens.

Viroids cause a number of
important plant diseases and
can have a severe agricultural
impact
Causing

growth stunRng,
No viroids are known that infect a at top,
animals or prokaryotes.
premature plant

death

Viroids and plant

diseases

Potato

Viral Pathogenesis
Viral Pathogenesis is the process by which
a virus infecKon leads to infecKous disease


Viral Tropism
Viral tropism is the specicity of
viruses to enter and infect
parKcular host cells and is
determined in part by the ability
of viruses to bind to receptors on
those cells.

Viral Pathogenesis Mechanisms:

1. Cara masuk virus ke dalam tubuh
2. Replikasi pada lokasi infeksi
3. Penyebaran virus dan mulKplikasinya
pada organ target dimana penyakit
infeksi tsb terjadi
4. Diseminasi virus secara sistemik ke
organ-organ lain diseluruh tubuh

Pathogenic ProperKes of Viruses

Factors that aect pathogenic mechanisms are:
1. Accessibility of virus to Kssue: PenetraKon
ability
2. Cell suscepKbility to virus mulKplicaKon
(Cytopathic Eects of Viruses)
3. Virus suscepKbility to host defenses: Viruses
have a variety of mechanisms that enable
them to evade destrucKon by the hosts
immune response

Cytopathic Eects of Viruses

The visible eects of viral infecKon are known as
cytopathic eects (CPE):
1. cytocidal eects ! cell death
2. noncytocidal eects ! cell damage

CPEs are used to diagnose many viral infecKons

InfecKon of a host cell by an animal virus usually kills
the host cell
Death can be caused by
1. the accumulaKon of large numbers of mulKplying
viruses
2. the eects of viral proteins on the permeability of the
host cells plasma membrane
3. inhibiKon of host DNA, RNA, or protein synthesis

Cytopathic Eects of Selected Viruses

Infeksi virus pada target organ spesik

Sistem
Respirasi

Sistem
Saraf

Organ HaR Sistem

Pencernaan

Kulit &
Mata

Sistem limfaRk &

Kardiovaskular

Inuenza
H5N1
H1N1
Adenovirus
Rhinovirus
Coronavirus
SARS

Rabies
Polio

HepaKKs

Cacar
Herpes
Varicella-
zoster
Measles
Rubella
HPV

Epstein-Barr
CMV
HIV
Demam kuning
Dengue
Ebola
Chikunguya

Rotavirus
Calicivirus
Astrovirus
Torovirus
Adenovirus

Latent & Persistent Viral InfecKons

LATENT VIRAL INFECTION
A virus can remain in equilibrium
with the host and not actually
produce disease for a long
period, oaen many years.
Chicken pox virus (varicella
cacar)

PERSISTENT VIRAL INFECTION
A persistent or chronic viral
infecRon occurs gradually over
a long period. Typically,
persistent viral infecKons are
fatal.
Measles EncephaliKs

Pencegahan infeksi virus

Imunisasi

Cara meningkatkan imunitas seseorang terhadap

invasi m.o patogen/toksin

Vaksin

Suspensi m.o/substansi m.o induksi sistem

imunitas

Produk Immunoglobulin
Pemberantasan vektor virus & sanitasi lingkungan

Beberapa cara imunisasi untuk memperoleh kekebalan

tubuh

Buatan: Vaksinasi

AkRf
Alamiah: Infeksi
virus, bakteri, dll

Imunisasi
Pasif

Buatan:
AnKtoksin,
anKbodi
Alamiah: AnKbodi
dr plasenta dan
kolostrum

Tipe & Jenis vaksin untuk mencegah virus

Jenis Vaksin

Tipe vaksin

HepaKKs A

AnKgen virus yang dimaKkan

HepaKKs B

Rekombinan vaksin

Inuenza

AnKgen virus yang dimaKkan atau komponen virus

Adenovirus Kpe 4 & 7

AnKgen virus yang dilemahkan

Polio

AnKgen virus yang dimaKkan

Japanese enchepaliKs

AnKgen virus yang dimaKkan

Vaksin Oral Poliovirus

AnKgen virus yang dilemahkan

Rabies

AnKgen virus yang dimaKkan

Smallpox

AnKgen virus yang dilemahkan

Varicella

AnKgen virus yang dilemahkan

Demam kuning

AnKgen virus yang dilemahkan

Fusion
inhibitor
SyntheRc
amines

RNA
polymerase
inhibitor

Interferons

Neuraminidase
inhibitors

AnRviral
Drugs

Nonnucleoside
reverse
transcriptase
inhibitor (NNRTI)

Protease
inhibitors

NucleoRde
analogs

Nucleoside
analogs

AnRviral Drugs
Category/drug

Mechanism of ac5on

Virus aected

Fusion inhibitor
EnfuvirKde

Blocks HIVT lymphocyte

membrane fusion

HIV

Interferons
Interferons

Induces proteins that inhibit

viral replicaKon

Broad spectrum (host-specic)

Neuraminidase inhibitors
Oseltamivir (Tamiu)
Zanamivir (Relenza)

Block acKve site of inuenza

neuraminidase

Inuenza A & B

Nonnucleoside reverse
transcriptase inhibitor
(NNRTI)
Nevirapine

Reverse transcriptase inhibitor HIV

NucleoRde analogs (NtRTI)

Cidofovir

Tenofovir (TDF)

Viral polymerase inhibitor

Reverse transcriptase inhibitor
HIV

Cytomegalovirus,
herpesviruses
HIV

AnRviral Drugs
Category/drug

Mechanism of ac5on

Nucleoside analogs (NRTI)

Acyclovir
Ganciclovir
Triuridine
Valacyclovir
Vidarabine

Viral polymerase inhibitors

Herpes viruses, Varicella zoster
Cytomegalovirus
Herpesvirus
Herpesvirus
Herpesvirus, vaccinia, hepaKKs B
virus

Abacavir (ABC)
Reverse transcriptase
Didanosine (dideoxyinosine inhibitors
or ddI) Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Zalcitabine (ddC)
Zidovudine (AZT)
Ribavirin

Virus aected

HIV
HIV

HIV
HIV, hepaKKs B virus
HIV
HIV
HIV

Blocks capping of viral RNA Respiratory syncyKal virus, inuenza

A and B, Lassa fever

AnRviral Drugs
Category/drug

Mechanism of ac5on

Virus aected

Protease inhibitors
Amprenavir
Indinavir
Lopinavir
Nelnavir
Saquinavir

Viral protease inhibitor

HIV
HIV
HIV
HIV
HIV

Pyrophosphate analog
Phosphonoformic acid
(foscarnet)

Viral polymerase inhibitor

Herpesviruses, hepaKKs B virus

RNA polymerase inhibitor

Rifamycin

RNA polymerase inhibitor

Vaccinia, pox viruses

SyntheRc amines
Amantadine
Rimantadine

Viral uncoaKng blocker

Inuenza A
Inuenza A

Neuraminidase Inhibitor: Oseltamivir &

Zanamivir

Human Immunodeciency Virus

HIV

HIV 1

HIV 2

The genome of the retrovirus

is unique.

It consists of two idenRcal
single-stranded RNA
molecules of the plus (+)
orientaRon

HIV-Genome

gag, encoding structural proteins;

pol, encoding reverse transcriptase and integrase; and
env, encoding envelope proteins

HIV-1 Stucture

HIV Tranmission: Trends

HIV Life Cycle

1. Binding/aeachment
2. Fusion
3. Reverse TranscriptaRon
4. IntegraRon
5. TranscripRon &
TranslaRon
6. Assembly
7. Budding

HIV Life Cycle (ConKnue)

Summary: ReplicaKon of Retrovirus (HIV)

1. Entry into the cell by fusion with the cytoplasmic membrane at
sites of specic receptors
2. Removal of the virion envelope at the cytoplasmic membrane,
but the genome and virus-specic enzymes remain in the virus
core
3. Reverse transcripRon of one of the two idenKcal genomic RNA
molecules into a ssDNA that is subsequently converted by reverse
transcriptase to a linear dsDNA molecule, which then enters the
nucleus
4. IntegraRon of retroviral DNA into the host genome
5. TranscripRon of retroviral DNA, leading to the formaKon of viral
mRNAs and viral genomic RNA
6. Assembly and packaging of the two idenKcal genomic RNA
molecules into nucleocapsids in the cytoplasm
7. Budding of enveloped virions at the cytoplasmic membrane and
release from the cell

STAGES OF HIV INFECTION

Stages of HIV InfecKon:

CD4 vs Viral Load

HIV Treatment
The role of anKvirals is to slow or halt disease
progression
AnK Retrovirals Prolonged the life expectancy
of paKents, although not without some
important side eects
AnKretroviral treatments reduce HIV plasma
levels for as much and as long as possible
Several anKretroviral drugs are usually given
together to avoid emerging viral resistance

Highly AcRve AnR Retovirals Therapy (HAART)

HAART is the name given to aggressive

treatment regimens used to suppress HIV
viral replicaKon and the progression of HIV
disease
HAART regimen combines three or more
dierent drugs.
1. Two (2) NRTIs + (NNRTI) First line
Zidovudine + Lamivudine + Nevirapine

2. Two (2) (NRTIs) + a protease inhibitor (PI)

Second line

Tenofovir/Abacavir + Didanosin + Saquinavir

References
Tortora GJ, Funke BR, Case CL, 2013, Microbiology an
IntroducRon, 11th ediRon, Benjamin Cummings, San
Francisco, USA
Denyer SP, Hodges NA, Gorman SP, 2011, Hugo and
Russells: PharmaceuRcal Microbiology, 8th ediRon,
Blackwell Science Ltd., Blackwell Publishing Company,
USA
PraKwi ST, 2008, Mikrobiologi Farmasi, Erlangga,
Jakarta
Radji M, 2013, Buku Ajar Mikrobiologi Panduan
Mahasiswa Farmasi dan Kedokteran, Penerbit Buku
Kedokteran EGC, Jakarta
Radji M, 2010, Imunologi & Virologi, PT. ISFI
Penerbitan, Jakarta

Paper Work (10%)

Topik:
1. HepaRRs A,B,C virus
2. Inuenza A,B,C virus
3. Human Papillomavirus
(HPV)
4. Herpes Simplex Virus (HSV
1 & 2)
5. Varicella-Zoster Virus (V2V)
6. Cytomegalovirus (CMV)
7. Virus H5N1 (Bird) & H1N1
(Pig)
8. Measles virus
9. Chicken pox virus
10. Rubella virus

Content:
Struktur Virus
Siklus hidup Virus
Penyakit yang disebabkan
oleh virus serta
patogenesisnya
Vaksin atau anRvirus
disertai mekanismenya
(Obat)
Times New Roman (12), 1,5
space, A4
Maksimum 10 halaman
sudah termasuk cover
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