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Viruses-Basic Concepts Classification & General Structures Prof.Dr.Güner Söyletir • A virus is a piece of bad news wrapped in a protein coat -Peter Medawar- Viruses as a whole • the most abundant biological entity in aquatic environments • One teaspoon of seawater contains ~10 million viruses...
Viruses-Basic Concepts Classification & General Structures Prof.Dr.Güner Söyletir • A virus is a piece of bad news wrapped in a protein coat -Peter Medawar- Viruses as a whole • the most abundant biological entity in aquatic environments • One teaspoon of seawater contains ~10 million viruses • Essential to the regulation of saltwater and freshwater ecosystems Viruses as a whole • Most are bacteriophages (harmless to plant & animals) infect & destroy the bacteria in aquatic microbial communities the most important mechanism of recycling carbon in the marine environment • Microorganisms constitute more than 90% of the biomass in the sea. It is estimated that viruses kill approx. 20% of this biomass each day Viruses as a whole • Over 4,800 species of viruses have been described in detail out of the millions in the environment. • So small – invisible with light microscopy • A NUCLEIC ACID surrounded by a protein coat (CAPSID) • In some viruses lipid envelop Sizes of Viruses • The smallest viruses are ~20 nm in diameter • Typical size: 100 nm • Largest virus: Pandoravirus 1000 nm in length • Bacteria: 2000-3000 nm (2-3 μm) • Human cells: 10000-30000 nm (10-30 μm) 1 nm = 10-3 μm = 10-6 mm 1000 nm = 1 μm = 0,001 mm Pandoraviruses • is a genus of giant virus, first discovered in 2013. • have double stranded DNA genomes, with the largest genome size (2.5 million base pairs) of any known viral genus. • do not seem to be harmful to humans. • They are mostly found in marine environments, infecting amoebae Human viruses Virus • Nucleic acid DNA RNA double or single stranded • Protein coat • In some viruses lipid envelop Nucleic acid Capsid Envelope Symmetry of viral capsid Capsid (Protein coat) Most viruses have • Icosahedral (cubic achitecture) • Helical (cylindrical architecture) capsid structure Enveloped-cubic symmetry HIV Enveloped helical symmetry Influenza hemagglutinin Rabies Complex Viral Structure A few viruses : • Poxviruses-- Human • Geminiviruses-- Plant • Bacteriophages-- Bacteria Envelope / Matrix proteins /Viral Attachment Proteins • Envelope is a lipid membrane that is derived from one of the cell’s membrane - plasma membrane, ER, golgi complex or nuclear membrane • Matrix proteins connect the envelope to the capsid inside • Virus attachment proteins are embedded in outer-most layer Basic structures of viruses Naked Enveloped Virion : Infectious virus particle Properties of naked capsid viruses 19 Properties of enveloped viruses 20 Genome Composed of DNA or RNA but not both •Double stranded DNA - dsDNA •Single stranded DNA - ssDNA •Double stranded RNA - dsRNA •Single stranded RNA – ssRNA Sizes of viral genomes •7000 – 20000 base pairs (bp) 7-20 kb (A human cell contains over 3 billion bp) • Circular, linear or segmented arrangement HPV HSV Inluenza v. Classification of Viruses ICTV (International Committee for Taxonomy of Viruses) and Baltimore classifications • Nucleic acid sequence and G+C content • Size of the genome • Linear or circular • Positive or negative sense • Symmetry of the protein coat • Presence or absence of a lipid membrane Baltimore Classification of animal virus Classification of Human viruses 1. Type of Nucleic Acid DNA or RNA (Ss /Ds) Strategy of replication 2. Size & morphology Type of symmetry( Icosahedral, Helical,Complex) Number of capsomers (capsid subunits) Presence or absence of envelope 25 3. Presence of specific enzymes e.g: - RNA and DNA polymerase - Neuraminidase - Reverse transcriptase 4. Host tissue or cell tropism e.g: Hepatitis v., HIV, encephalitis v. etc 5.Mode of transmission e.g. Arboviruses 6. Host range e.g. Animal, bacteria, plant 26 DNA VIRUSES DOUBLE STRANDED ENVELOPED HERPESVIRIDAE HEPADNAVIRIDAE SINGLE STRANDED NON-ENVELOPED NON-ENVELOPED CIRCULAR PAPILLOMAVIRIDAE POLYOMAVIRIDAE (formerly grouped together as the PAPOVAVIRIDAE) PARVOVIRIDAE COMPLEX ds ENVELOPED POXVIRIDAE LINEAR ADENOVIRIDAE All families shown are icosahedral except for poxviruses 27 RNA VIRUSES SINGLE STRANDED +sense ENVELOPED ICOSAHEDRAL FLAVIVIRIDAE TOGAVIRIDAE RETROVIRIDAE HELICAL CORONAVIRIDAE SINGLE STRANDED DOUBLE STRANDED - sense NONENVELO PED ICOSAHEDRAL PICORNAVIRIDAE CALICIVIRIDAE ENVELOPED HELICAL ORTHOMYXOVIRIDAE PARAMYXOVIRIDAE RHABDOVIRIDAE FILOVIRIDAE BUN YAVIRIDAE ARENAVIRIDAE NONENVELOPED ICOSAHEDRAL REOVIRIDAE Families of Human Viruses dsDNA viruses Examples Hepadnaviridae Hepatitis B Virus Papillomaviridae Human Papilloma virus Adenoviridae Adenovirus Herpesviridae Polyomaviridae Herpes simplex Virus JC Polyomavirus Poxviridae Variola ssDNA viruses Parvoviridae Parvovirus B19 Families of Human Viruses dsRNA viruses Reoviridae Examples Rotavirus + ssRNA viruses Coronaviridae Flaviviridae Picornaviridae SAR S-Cov-2 (COVID-19) Hepatitis C Virus Poliovirus, Hepatitis A virus Families of Human Viruses -ssRNA viruses Examples Bunyaviridae Rhabdoviridae Crimean-Congo Hem. Fever V. Rabies virus Filoviridae Ebola virus Orthomyxoviridae Influenza A virus Families of Human Viruses RNA virus that reverse transcribe Retroviridae Human Immunodeficiency virus-1 DNA virus that reverse transcribe Hepadnaviridae Hepatitis B Virus Important Facts about Viral Replication • Multiply only in living cells (obligate intracellular parasites) • Host cell provides the energy & machinery for the synthesis of viral proteins & nucleic acids • Viral genome must be able to produce mRNA Viral Replication Cycle • Adsorption (Attachment to the host cell) • Penetration & entry • Uncoating • Replication (Virion component production) • Assembly • Maturation • Release from the cell Viral Replication Cycle Adsorption Enveloped viruses Naked viruses HIV Poliovirus, Adenovirus, Adsorption HIV CD4 Influenza Virus Sialic Acid Adsorption of SAR S-Cov-2 ACE2 Penetration Fusion HIV Endocytosis Influenza, Herpes Uncoating Viral capsid is broken by viral or cellular enzyme Replication / Assembly / Maturation Replication • DNA viruses in nucleus (except Poxviruses) • RNA viruses in cytoplasm (mainly) • Viruses must make mRNA • Translation of viral proteins by host ribosomes • They use host cell protein synthesis machinery Positive & negative sense RNA Positive sense RNA can be translated directly into protein(acts as mRNA) Negative sense RNA must be transcribed into mRNA by a virus encoded RNA dependent RNA polymerase 43 Replication of dsDNA viruses dsDNA viruses Examples Adenoviridae Adenovirus Herpesviridae Herpes simplex Virus Polyomaviridae JC Polyomavirus Papillomavaviridae Human Papilloma virus Poxviridae Variola Replication of dsDNA viruses (except Poxvirus) Viral DNADNA dep. mRNA Cytoplasm host RNA poly. Viral DNA Nucleus Early proteins (DNA polymerase, etc.) mRNA Late proteins (viral capsid, matrix prot.) Fusion with plasma membrane and release Replication of +ssRNA viruses + ssRNA viruses Coronaviridae COVID-19 Flaviviridae Picornaviridae Hepatitis C Virus Poliovirus, Hepatitis A virus Replication of + ssRNA viruses Single polypeptide +mRNA Proteins RNA polymerase capsid, etc. Viral RNA polymerase - RNA +RNA Assembly + RNA virions In cytoplasm Replication of -ssRNA viruses -ssRNA viruses Examples Bunyaviridae Rhabdoviridae Crimean-Congo Hem. Fever V. Rabies virus Filoviridae Ebola virus Orthomyxoviridae Influenza A virus Replication of - ssRNA viruses Viral RNA polymerase -RNA influenza, parainfluenza, Rubeola, Mumps +mRNA Proteins (capsid etc.) -RNA Assembly - RNA virions Replication of RNA virus that reverse transcribe RNA virus that reverse transcribe Retroviridae Human Immunodeficiency virus-1 +RNA +RNA -DNA +DNA -DNA +RNA Retroviruses / HIV two identical copies of +RNA (diploid) Reverse transcription Integration Transcription by host RNA polymerase Replication of DNA virus that reverse transcribe DNA virus that reverse transcribe Hepadnaviridae Hepatitis B virus mechanistically similar to that of a retrovirus. the viral DNA is transcribed to produce a single-stranded RNA reverse transcribed to produce the progeny viral DNA encapsidated into virions Release of Virions Enveloped viruses 1-Budding from plasma membrane 2-Budding from ER & Golgi etc. Exocytosis Naked viruses Accumulate in cytoplasm Released by burst of host cell Release by budding from plasma membrane Release by Budding & Exocytosis Release by Burst Bacteriophages (Viruses of bacteria Bacteriophages Viruses of bacteria Infection ; - Lytic - Lysogenic Lytic Infection Lysogenic Infection Subviral Particles: SATELLİTE (Defective) VIROIDS PRIONS Defective virus Hepatitis Delta virus Hepatitis B virus Viroids • Circular, ssRNA molecules ( 350-375 bp) • No protein coat • Plant pathogens PRIONS • Smaller than viruses (25 nm) • Transmissible to animals • Replication to high titers • Do not contain nucleic acids (Infectious proteins) Prions • A type of protein that can trigger normal proteins in the brain to fold abnormally. • Prion diseases can affect both humans and animals • May spread to humans by infected meat products. • The most common form of prion disease that affects humans is Creutzfeldt-Jakob disease (CJD).