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Viruses, Viroids, and Prions
Mariana Wahyudi (FF) Maret 2012
3/26/2012 1
Definisi
Virus
suatu partikel non-sellular yang tersusun atas materi
genetik dan protein yang dapat menginvasi sel-sel hidup.
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Virus
• Mengandung DNA atau RNA dan selubung protein
• Beberapa dibungkus oleh selubung / envelope (lipida,
protein, dan karbohidrat)
• Sebagian virus memiliki duri-duri (spikes)
• Sebagian besar virus menginfeksi hanya tipe sel-sel spesifik dalam suatu inang.
• Host range ditentukan oleh sisi perlekatan spesifik pada inang dan faktor-faktor selular
• Parasit intraselular mutlak (obligat), menyebabkan sintesis element khusus yang memindahkan asam nukleat viral ke sel-sel lainnya.
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Penemuan Virus
• Mayer (1886), penyakit tobacco mosaic bisa ditularkan ke tanaman sehat
• Iwanowski (1892), juice disaring dengan filter, filtratnya bisa menyebabkan tanaman lain “sakit” ?
• Beijerinck (1897) memberi nama “virus” artinya poison
copyright cmassengale
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Tobacco Mosaic Virus
• Wendell Stanley (1935) mengkristalkan virus tobacco
• Penemuan: virus terdiri dari asam nukleat dan protein
copyright cmassengale
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Human viruses
• 1980 – 1990 kemajuan di bidang teknik biologi molekular, penyingkapan adanya virus manusia
• 1983 Human immunodeficiency virus (HIV) ditemukan
• Hantavirus Sin Nombre, dari binatang pengerat, menyebabkan infeksi pada banyak orang di Amerika Selatan
• 1999, West Nile Virus diketahui sebagai penyebab kasus encephalitis di New York
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Smallpox
• Edward Jenner (1796) penemu vaksin cacar (cowpox virus yang dilemahkan)
• Virus aktif (mematikan) disebut virulent
• Sejak itu kata virulent jadi populer di dunia medis
copyright cmassengale
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Ukuran Virus
Figure 13.1
nm = 10-9 m
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Helical Viruses
• Virus-virus helikal tampak terlihat seperti benang panjang atau terputar.
• Kapsidnya berbentuk silinder berlubang di bagian tengah yang melingkupi DNA/RNA.
Virion = partikel virus komplet yang berkembang penuh, asam nukleat dikelilingi oleh selubung.
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Describe the chemical composition and physical structure of an enveloped and a nonenveloped virus
Figure 13.4a, b
Enveloped Helical Virus
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• Virus mengandung DNA atau RNA, tidak pernah kedua-duanya. • Asam nukleat bisa single atau double-stranded, linear atau
sirkular, atau terbagi menjadi beberapa molekul terpisah
Nonenveloped Polyhedral Viruses
Figure 13.2a, b
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Complex Viruses
Figure 13.5a
• Kapsid – selubung protein mengelilingi asam nukleat • Tersusun atas kapsomer, tunggal atau berbagai protein
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Growing Viruses
• Viruses must be grown in living cells.
– Bacteriophages form plaques on a lawn of bacteria.
– Easiest to grow
Figure 13.6
Describe how bacteriophages are cultured
Uninfected mouse cells form monolayer (left). Infected cells 24 hours later pile up and round up (right).
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Growing Viruses
• Viruses must be grown in living host cells
• Animal viruses may be grown in living animals or in embryonated eggs.
Figure 13.7
Describe how animal viruses are cultured
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Growing Viruses
• Animal and plants viruses may be grown in cell culture.
– Continuous cell lines may be maintained indefinitely
• Cytopathic effects due to viral growth
Figure 13.8
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• Cytopathic effects
• Serological tests
– Detect antibodies against viruses in a patient
– Use antibodies to identify viruses in neutralization tests, viral hemagglutination, and Western blot
• Nucleic acids
– RFLPs – restriction fragment length polymorphisms
– PCR – polymerase chain reaction (used to identify West Nile virus in US in 1999)
Virus Identification List 3 techniques that are used to identify viruses
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Virus Identification
Figure 13.9
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• Attachment Phage attaches by tail fibers to host cell
• Penetration Phage lysozyme opens cell wall, tail sheath contracts to force tail core and DNA into cell
• Biosynthesis Production of phage DNA and proteins
• Maturation Assembly of phage particles
• Release Phage lysozyme breaks cell wall
Multiplication of Bacteriophages (Lytic Cycle)
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Attachment: Phage attaches to host cell.
Penetration: Phage pnetrates host cell and injects its DNA.
Biosynthesis: Production of phage DNA and proteins
1
2
3
Bacterial cell wall
Bacterial chromosome
Capsid
DNA
Capsid
Sheath Tail fiber
Base plate
Pin
Cell wall
Tail
Plasma membrane
Sheath contracted
Tail core
Describe the lytic cycle of T-even bacteriophages
Lytic cycle of T-even bacteriophage
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Figure 13.10.2
4 Maturation: Viral components are assembled into virions.
Tail
5 Release: Host cell lyses and new virions are released.
DNA
Capsid
Tail fibers
Lytic cycle of T-even bacteriophage
Burst time is generally about 20 – 40 minutes after phage absorption. Burst size ranges from 50 to 200 new phage cells.
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One-step Growth Curve for bacteriophage
Figure 13.11
During biosynthesis and maturation, separate components of DNA and protein may be detected in the host cell
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• Lytic cycle Phage causes lysis and death of host cell
• Lysogenic cycle Prophage DNA incorporated in host DNA
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The Lysogenic Cycle
Figure 13.12
Describe the lysogenic cycle of bacteriophage lambda.
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Specialized Transduction
Figure 13.13
Prophage exists in galactose-using host (containing the gal gene).
Phage genome excises, carrying with it the adjacent gal gene from the host.
Phage matures and cell lyses, releasing phage carrying gal gene.
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2
3
Prophage
gal gene
gal gene Bacterial DNA
Galactose-positive donor cell gal gene
Phage infects a cell that cannot utilize galactose (lacking gal gene).
4
Galactose-negative recipient cell
Along with the prophage, the bacterial gal gene becomes integrated into the new host’s DNA.
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Lysogenic cell can now metabolize galactose.
6
Galactose-positive recombinant cell 3/26/2012 25
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• Attachment Viruses attaches to cell membrane
• Penetration By endocytosis or fusion
• Uncoating By viral or host enzymes
• Biosynthesis Production of nucleic acid and proteins
• Maturation Nucleic acid and capsid proteins assemble
• Release By budding (enveloped viruses) or rupture
Multiplication of Animal viruses
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Attachment, Penetration and Uncoating
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Compare and contrast the multiplication cycle of DNA- and RNA-containing animal viruses
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
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RNA-containing animal viruses: rubella (left), mouse mammary tumor virus (right). Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
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Release of an enveloped virus by budding
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Most enveloped viruses take part of host’s plasma membrane for their envelope
(a) Release by budding (b) Alphavirus
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Cancer
• Activated oncogenes transform normal cells into cancerous cells. (malignant transformation)
• Transformed cells have increased growth, loss of contact inhibition, tumor specific transplant and T antigens, chromosome abnormalities, can produce tumors when injected into susceptible animals.
• Several DNA viruses and retroviruses are oncogenic.
• The genetic material of oncogenic viruses becomes integrated into the host cell's DNA.
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Define oncogene and transformed cell.
Oncogenic Viruses
Oncogenic DNA Viruses
• Adenoviridae
• Heresviridae
• Poxviridae
• Papovaviridae
• Hepadnaviridaeridae
Oncogenic RNA viruses
• Retroviridae – Viral RNA is transcribed to
DNA which can integrate into host DNA
– HTLV 1
– HTLV 2
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Retroviruses carry reverse transcriptase which allows RNA to DNA, permitting oncogenic properties
Discuss the relationship of DNA- and RNA-containing viruses to cancer
• Latent Viral Infections
– Virus remains in asymptomatic host cell for long periods
• Cold sores, shingles
• Persistent s)Viral Infections
– Disease processes occurs over a long period, generally fatal
• Subacute sclerosing panencephalitis (measles • vi
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Provide an example of a latent viral infection.
Differentiate between persistant viral infections and latent viral infections.
• Persistent viral infections are caused by conventional viruses, occur over a long period, generally fatal.
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 3/26/2012 39
Some Plant Viruses
Name a virus that causes a plant disease
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Taksonomi Virus
• Klasifikasi didasarkan pada tipe asam nukleat, replikasi, dan morfologi.
• Nama keluarga (Family) diakhiri dengan -viridae
• Nama genus diakhiri dengan -virus
• Spesies virus: kelompok virus yang memiliki informasi genetik dan ecological niche (host) yang sama. Nama-nama umum digunakan untuk spesies.
• Subspesies ditandai dengan nomor
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Define viral species
Contoh penamaan virus
• Herpesviridae
• Herpesvirus
• Human herpes virus 1, HHV 2, HHV 3
Retroviridae Lentivirus Human Immunodeficiency Virus 1, HIV 2
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Virus Families
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Karakteristik/dimensi Virus Families Genus penting Clinical or special features
Single-stranded DNA, non-enveloped 18-25 nm
Parvoviridae
Human parvovirus
Fifth disease ; Anemia in immunocompromised patients
Double-stranded DNA, nonenveloped 70-90 nm
Adenoviridae Mastadenovirus Respiratory infections in humans; tumors in animals
40-57 nm Papillomavirus (human wart virus) Polyomavirus
Cause tumors, some cause cancer
Double-stranded DNA, enveloped 200-250 nm
Hepadnavirus (Hepatitis B virus)
Use reverse transcriptase to produce DNA from mRNA
Double-stranded DNA, nonenveloped viruses
• Simplexvirus (HHV1 and HHV 2
• Varicellavirus (HHV 3)
• Lymphocryptovirus (HHV 4)
• Cytomegalovirus (HHV 5)
• Roseolovirus (HHV 6)
• HHV 7
• Kaposi's sarcoma (HHV 8) – Some herpesviruses can
remain latent in host cells
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Virus Families
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Karakteristik/dimensi Virus Families Genus penting Clinical or special features
Double-stranded DNA, non-enveloped 200-250 nm
Poxviridae Orthopoxvirus (vaccinia and (vaccinia and smallpox viruses) Molluscipoxvirus
Very large, brick-shaped viruses that cause diseases such as smallpox (variola), molluscum contagiosum (wortlike skin lession), and cowpox
Single-stranded RNA, + strand, nonenveloped
• Hepatitis E virus
• Norovirus (Norwalk agent) causes gastroenteritis
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• Enterovirus
– Enteroviruses include poliovirus and coxsackievirus
• Rhinovirus
• Hepatitis A virus
Single-stranded RNA, + strand, nonenveloped
• Arboviruses can replicate in arthropods; include yellow fever, dengue, SLE, and West Nile viruses
• Hepatitis C virus
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• Alphavirus
– Alphaviruses are transmitted by arthropods; include EEE, WEE
• Rubivirus (rubella virus)
Single-stranded RNA, + strand, nonenveloped
• Coronavirus
– Upper respiratory infections
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Single-stranded RNA, – strand, one RNA strand
• Vesiculovirus
• Lyssavirus (rabies virus)
– Cause numerous animal diseases
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• Filovirus
– Enveloped, helical viruses
• Ebola and Marburg viruses
• Hepatitis D virus
– Depends on coinfection with Hepadnavirus
Single-stranded RNA, – strand, multiple RNA strands
• Influenzavirus
(Influenza viruses A and B)
• Influenza C virus
– Envelope spikes can agglutinate RBCs
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Single-stranded RNA, – strand, multiple RNA strands
• Bunyavirus (CE virus)
• Hantavirus
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• Arenavirus
– Helical capsids contain RNA containing granules
– Lymphocytic choriomeningitis
– VEE and Lassa fever
• Lentivirus (HIV)
• Oncogenic viruses
– Use reverse transcriptase to produce DNA from viral genome
– Includes all RNA tumor viruses
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Double-stranded RNA, nonenveloped
• Reovirus (Respiratory Enteric Orphan)
• Rotavirus
– Mild respiratoryinfections and gastroenteritis
• Colorado tick fever
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Prions
• Infectious proteins first discovered in 1980’s
• Inherited and transmissible by ingestion, transplant, & surgical instruments
• Spongiform encephalopathies: Sheep scrapie, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, mad cow disease
• PrPC, normal cellular prion protein, on cell surface
• PrPSc, scrapie protein, accumulate in brain cells forming plaques
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Discuss how a protein can be infectious
Prions How a protein can be infectious: if an abnormal prion proteinenters cell, it changes a normal prion to PrPSc, which changes another normal PrP (accumulation of abnormal PrPSc)
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Linear and circular potato spindle tuber viroid
• Plant Viruses – Plant viruses enter
through wounds or via insects
• Viroids – Viroids are infectious
RNA; potato spindle tuber disease
• Prion = infectious protein
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Differentiate between virus, viroid, and prion.