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RNA VIRUS drh. Sruti Listra Adrenalin, M.Sc. 10 Maret 2020

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RNA VIRUSdrh. Sruti Listra Adrenalin, M.Sc.

10 Maret 2020

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KLASIFIKASI BALTIMORE

RNA VIRUS 1• dsRNA (Class III):

1. Reoviridae

2. Birnaviridae

• ssRNA (+) (class IV):

1. Coronaviridae

2. Flaviviridae

3. Caliciviridae

4. Picornaviridae

5. Togaviridae

RNA VIRUS 2• ssRNA (-) (Class V):

1. Bunyaviridae

2. Orthomyxoviridae

3. Filoviridae

4. Bornaviridae

5. Paramyxoviridae

6. Rhabdoviridae

• ssRNA (RT) (Class VI):

1. Retroviridae

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RNA VIRUSES

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BUNYAVIRIDAE• Four genera infect vertebrates: (arthropod-borne) Bunyavirus

Phlebovirus, and Nairovirus; (nonarthropod-borne) Hantavirus.

• The family Bunyaviridae is the largest virus family, with more than

350 member viruses.

• Virions are spherical (±80.120nm diameter), lipid enveloped, 80-110 nm in diameter.

• Virions have glycoprotein spikes but no matrix protein in their envelope.

• Segmented negative-sense, ssRNA genome; three segments—L (large), M (medium), and S (small)—total 1119 kb in size.

• Cytoplasmic replication; budding into Golgi vesicles.

• Generally cytocidal for vertebrate cells, but noncytocidal persistent infection in invertebrate cells.

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… BUNYAVIRIDAE

• Orthobunyavirus, Nairovirus, and Phlebovirus maintained in vertebratearthropod cycles (ie, arboviruses) arthropod vectors (specific mosquitoes, ticks, midges, or biting flies) and vertebrate reservoir hosts cause transient infection (vertebrate hosts), life-long persistent infection (arthropod vectors).

• Hantaviruses are disseminated by specific rodents.

• Antigenic determinants on the nucleocapsid protein to define broad groupings among the viruses.

• Epitopes on the envelope glycoproteins (targets in neutralization and hemagglutination-inhibition assays) define serogroups.

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… BUNYAVIRIDAE

• The genus Phlebovirus contains over 50 viruses, all of which are transmitted by sandflies or mosquitoes (Rift Valley fever virus).

• The genus Nairovirus contains a large number of viruses, most of which are tick-borne.

• All bunyaviruses have at least four virion proteins: two external glycoproteins (Gn, Gc), the L protein (transcriptase), and the N protein (nucleoprotein).

• Sensitive to heat and acid conditions, inactivated by detergents, lipid solvents, and common disinfectants.

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Famili Bunyaviridaeyang Patogen padaHewan dan Manusia

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ORTHOMYXOVIRIDAE

• Six genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Thogotovirus, Isavirus, and Quaranjavirus.

• The genome consists of linear negative-sense, ssRNA.

• Virions are pleomorphic, spherical, or filamentous, 80.120 nm in diameter, and consist of an lipid envelope with large glycoprotein spikes surrounding 6-8 helically symmetrical nucleocapsid segments of different sizes.

• There are two kinds of spikes (influenza A & B virus); rod shaped (consisting of homotrimers of the hemagglutinin glycoprotein), and mushroom shaped (consisting of homotetramers of the neuraminidase protein).

• Transcription and RNA replication nucleus; budding takes place on the plasma membrane.

• Defective interfering particles and genetic reassortment occur frequently.

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… ORTHOMYXOVIRIDAE

• Greek “myxa” mucus.

• Influenza C viruses lack a distinct neuraminidase spike, and have a single kind of glycoprotein spike that consists of multifunctional hemagglutinin-esterase molecules.

• Three functions are linked to the surface proteins: receptor binding, receptor cleavage, and membrane fusion.

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… ORTHOMYXOVIRIDAE

• The emergence of variant viruses depends not only on genetic drift (point mutations: nucleotide substitutions, insertions, deletions), but also on genetic shift (genomic segment reassortment).

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Antigenik shift Antigenik drift

Perubahan mayor antigenik Perubahan minor antigenic

Terbentuk subtype baru Terbentuk strain baru

Melibatkan 1 atau 2 virus Melibatkan 1 virus

Terjadi sekali dlm 1 waktu Sering terjadi (frequently)

Dapat menginfeksi spesies yg berbeda (hewanke manusia)

Menginfeksi hewan dari spesies yg sama

Terjadi perubahan yg besar pd RNA nukleotid Terjadi mutase kecil RNA

Terjadi sbg hasil dari bermacam-macamgenom antara subtype yg berbeda

Terjadi sbg hasil dari akumulasi poin mutase gen.

Mutasi besar dan tiba-tiba Mutasi acak dan spontan

Susah diobati (membutuhkan vaksin baru) Gampang diobati (ab dan obat lain)

Hanya terjadi pd tipe virus influenza A Terjadi pd virus influenza A,B,C

Menyebabkan pandemic, terjadi ireguler, tidak terprediksi

Menyebabkan epidemic

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… ORTHOMYXOVIRIDAE

• Influenza A viruses are categorized into 16

hemagglutinin (H) and 9 neuraminidase (N) subtypes.

• The first HPAI virus of the H5 subtype.

• A/chicken/Scotland/1959 (H5N1); A/Hong Kong/1/1968 (H3N2); A/swine/Iowa/15/1930 (H1N1).

• C/. clade 2.1, 2.2, 2.1.3, 2.2.1, 2.1.3.2

• Influenza viruses are sensitive to heat (56°C, 30 minutes), acid (pH 3), and lipid solvents, very labile under ordinary environmental conditions.

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Transmission

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Replication

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FILOVIRIDAE• Virions are pleomorphic, appearing as long filamentous forms and other shapes; they

have a uniform diameter of 80 nm and vary greatly in length (unit nucleocapsidlengths of about 800 nm for Marburg and 1000 nm for Ebola virus).

• Virions are composed of a lipid envelope covered with spikes surrounding a helically nucleocapsid.

• The genome is composed of a single molecule

of negative-sense, ssRNA,

19.1 kb in size.

• Infection is extremely cytopathic in cultured

cells and in target organs of host.

• Marburg dan Ebola.

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… FILOVIRIDAE

• The family Filoviridae contains three genera: Marburgvirus, Ebolavirus, Cuevavirus.

• Cytoplasmic replication, large intracytoplasmic inclusion bodies, budding from the plasma membrane.

• Virus dari family Filoviridae menarik, karena:

1. Walaupun mirip dengan anggota lain dari ordo Mononegavirales(Paramyxoviridae, Rhabdoviridae, dan Bornaviridae), namun secara morfologigenom dan cara replikasinya berbeda.

2. Menyebabkan wabah yg besar pd manusia dan berpotensi mjd epidemik (Ebola th2013-2016) di Afrika Barat 28.000 terinfeksi (11.000 mati).

3. Menimbulkan klinis pd manusia dan primate, kerusakan jaringan cepat, mortalitastinggi.

4. Zoonosis kelelawar buah mjd reservoir Ebola dan Marburg BSL 4.

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… FILOVIRIDAE

• All nonsegmented negative-sense RNA viruses share several characteristics:

1. a similar genome organization and roughly the same gene order.

2. a virion-associated RNA polymerase (transcriptase).

3. a helical nucleocapsid.

4. transcription of messenger RNAs (mRNAs) from a single promoter.

5. virion maturation via budding of preassembled nucleocapsids from the cellular plasma membrane at sites containing patches of viral glycoprotein spikes (peplomers).

• Infectivity stable at room temperature, but sensitive to ultraviolet and gamma irradiation, detergents, and common disinfectants.

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BORNAVIRIDAE

• Virions are spherical (± 90 nm in diameter),

enveloped with an inner core.

• The genome is a single molecule of negative-

sense, ssRNA, 8.9 kb in size.

• Transcription and replication nucleus. Infection in cell culture is noncytolyticand persistent infection (infections of animals and in cell cultures).

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… BORNAVIRIDAE• The major structural proteins: the nucleoprotein (N), the phosphoprotein (P), the

matrix protein (M), the glycoprotein (G), and the RNA-dependent RNA polymerase (L) protein.

• a single genus Bornavirus, that currently includes at least five distinct virus species:

1. Mammalian 1 bornavirus including classical Borna disease virus and the variant No/98.

2. Psittaciform 1 bornavirus that includes avian/psittacine bornaviruses 1, 2, 3, 4, 7.

3. Passeriform 1 bornavirus including avian/canary bornaviruses C1, C2, C3, and LS.

4. Passeriform 2 bornaviruses including estridild finch bornavirus EF.

5. Waterbird 1 bornaviruses that include avian bornavirus 062cg.

• The virus is sensitive to heat, acid, lipid solvents, and common disinfectants

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PARAMYXOVIRIDAE

• Paramyxovirus virions are pleomorphic, 150.350 nm in diameter, as spherical or filamentous particles.

• Virion covered with large glycoprotein spikes (814 nm in length).

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… PARAMYXOVIRIDAE

• The family Paramyxoviridae, containing the genera Aquaparamyxovirus, Avulavirus, Ferlavirus, Henipavirus, Morbillivirus, Respirovirus, and Rubulavirus

• Virions are enveloped (contains two or three viral glycoproteins and one or two nonglycosylated proteins).

• Virions contain a “herringbone-shaped” helically symmetrical nucleocapsid, 600.800 nm in length, and 18 nm in diameter.

• Genome consists of a single linear molecule of negative-sense, ssRNA, 1319 kb in size.

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… PARAMYXOVIRIDAE

• Envelope spikes are composed of 2 glycoprotein: fusion protein (F) and HN/ H/ G key roles in pathogenesis of all paramyxovirus infection.

• F: fusion viral envelope with plasma membrane host cell.

• HN/ H/ G: attachment to cellular receptors.

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… PARAMYXOVIRIDAE

• Cytoplasmic replication, budding from the plasma membrane.

• Syncytium formation, intracytoplasmic and intranuclear inclusion bodies (genus Morbillivirus).

• Differentiate the individual families of the order include genome size, nucleocapsid structure, site of genome replication and transcription, manner and extent of messenger RNA (mRNA) processing, virion size and morphology, tissue specificity, host range, and pathogenic potential in their respective hosts.

• Ex. Rinderpest, canine distemper, Newcastle disease, measles, and mumps viruses

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… PARAMYXOVIRIDAE

• Have been named according to their species of origin (eg, porcine rubulavirus, avian paramyxoviruses 212), geographic sites of discovery (eg, Sendai, Hendra, and Newcastle disease viruses), antigenic relationships (eg, human parainfluenza viruses 15), or produce in affected animals or humans (eg, canine distemper, rinderpest, measles, and mumps viruses).

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RHABDOVIRIDAE

• Virions 45.100 nm in diameter, 100.430 nm long, contain a lipid.

• ssRNA sense -, bullet shaped (some are longer, some shorter), consist

of a helically coiled cylindrical nucleocapsid surrounded by an

envelope with large (510 nm in length) glycoprotein spikes.

• Cytoplasmic replication.

• Maturation is by budding through the plasma membrane.

• Some viruses, such as vesicular stomatitis viruses rapid

cytopathology; Rabies virus noncytopathogenic.

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… RHABDOVIRIDAE

• Nucleotides that encode five genes:

1. N: the nucleoprotein gene that encodes the major component of the viral nucleocapsid.

2. P is a phosphoprotein that serves as a cofactor for the viral polymerase.

3. M is an inner virion protein that facilitates virion budding.

4. G is the glycoprotein that forms trimers that make up the virion surface spikes.

5. L is the RNA-dependent RNA polymerase that functions in transcription and RNA replication.

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… RHABDOVIRIDAE

• Some rhabdoviruses transmitted by arthropod vectors.

• The family Rhabdoviridae important pathogens of mammals rabies, vesicular stomatitis, and bovine ephemeral fever viruses.

• Lyssavirus (Lyssa “the spirit of mad rage”) Rabies.

• Certain terrestrial mammals are reservoir hosts of rabies virus, and bats are potential reservoirs of both rabies and the rabies-like viruses.

• Rhabdoviruses are relatively stable in the environment (cool, moist environments, pH is alkaline); thermolabile and sensitive to the ultraviolet irradiation of sunlight.

• Rhabdovirus species are distinguished genetically (by partial sequencing) and serologically, most importantly by neutralization tests.

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RETROVIRIDAE

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… RETROVIRIDAE

• Retro “backward”, have 2 subfamilies (Orthoretrovirinae, Spumaretrovirinae), 7 genera.

• Oncogenic (Alpharetrovirus, Betaretrovirus, Gammaretrovirus, Deltaretrovirus, Epsilonretrovirus): ability the viruses to transform infected cells.

• Lentivirus (Lenti “slow”): prolonged incubation period between initial infection to occurrence of disease.

• Spumaviruse (Spuma “foam”): tendency to cause distinctive and characteristic vacuolation of the cytoplasm of infected cells.

• Diseases induced depending on the individual virus and its associated disease pathogenic mechanisms inflammation, neurodegeneration, immunodeficiency, and cellular transformation (neoplasia).

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… RETROVIRIDAE

• Virions are enveloped, 80-100 nm in diameter, and have a three-layered structure: an innermost genomenucleoprotein complex with helical symmetry, surrounded by an icosahedral capsid, in turn surrounded by an envelope with glycoprotein peplomers.

• Virions assemble at and bud from plasma membrane.

• Some retroviruses produce tumors (leukemias and sarcomas); members of the genus Lentivirus neurologic disease, arthritis, generalized chronic debilitating disease, or acquired immunodeficiency syndromes

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… RETROVIRIDAE

• 4 main genes: gag, pro, pol, and env.

1. Gag: encodes the major structural nonglycosylated polyproteins: specifically, matrix (MA), capsid (CA), and nucleocapsid (NC).

2. Pro: encodes a protease viral protein maturation.

3. Pol: encodes the multifunctional protein (the reverse transcriptase (RT) and integrase enzyme functions).

4. Env: encodes the antigenic surface glycoproteins (SU) and transmembrane protein (TM).

• Alpharetrovirus: Avian leucosis, sarcoma

• Lentivirus: Bovine immunodeficiency virus, Jembrana disease

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Replication

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REFERENCES

• Amri, I,A., Qosimah, D., Nugroho, W. 2019. Pengantar Virologi Veteriner. UB Press.

• MacLachlan, N.J., Dubovi, E.J. 2016. Fenner’s Veterinary Virology 5th Edition. Academic Press is an Imprint of Elsevier.

• Murphy, F.A., Gibbs, E.P.J., Horzinek, M.C., Studdert, M.J. 1999. Veterinary Virology 3rd Edition. Academic Press.

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