Lec 1 (Virus Structure) PDF

# Virus Structure ## Vet Nerd Team ### Some Definitions * **Virus** * Metastable, infectious, submicroscopic Very minute (Ultra filterable, obligatory (mandatory) intracellular need living cell, agent contain genetic material (DNA or RNA but never both) * (Toxic = Poison) Hepadna & Retro *...

# Virus Structure ## Vet Nerd Team ### Some Definitions * **Virus** * Metastable, infectious, submicroscopic Very minute (Ultra filterable, obligatory (mandatory) intracellular need living cell, agent contain genetic material (DNA or RNA but never both) * (Toxic = Poison) Hepadna & Retro * **Virion** * complete mature infectious virus particle * consists of single molecule of nucleic acid surrounded by protein coat. * Simplest virus consist of → viral genome (core) + viral protein (capsid) * **Viroid** * small self-replicative single stranded circular RNA molecule that can cause infection in plant only (Not in human or animal) * → Subviral agent * **Virusoid** * type of viroid that can't complete its life cycle inside plant cell without helper virus so helper virus must be present to give its capsid viroid capsid * **Prion** * - Satellite V. → virusoid but in animals * → Ex → Hepatitis D V. (Needs Hepatitis B V. to get capsid and complete its infectious cycle) * infectious polypeptide protein (in capsid without nucleic acid) * -Ex → cow madness infectious protein ### Facts About Viruses * Viruses can infect all types of life creatures → animals & plants & microorganisms (bacteria & protozoa) * Outside cell → virus is metabolically inert. * → Once virus enters cell → replicates Itself by genome replication and not by binary fission. * virus has neither cell wall nor a complete enzymatic system * → so unlike other microorganisms it is resistant to antibiotics (with minor exceptions **Neomycin**). * → antivirals and cellular glycoproteins (interferons) → have great and direct effects on viruses. ### Differences Between Viruses And Other M.Os | Property | Virus | Bacteria & Mycoplasma & Rickettsia & Chlamydia | | -------------- | ------------------ | ----------------------------------------- | | Genome | Either DNA or RNA | DNA + RNA | | Infectious genome | + | + | | Binary fission | - | + | | Metabolic activity | - | + | | Ribosomes | - | + | | Sensitivity to antibiotics | + | + | | Sensitivity to interferons | - | + | | Growth on artificial media | - | Only bacteria & mycoplasma | ## Virus Structure * Virus majorly composed of 2 Components → * 1st internal one→ genetic material (genome or Core or Chromosome or nucleic acid) → DNA or RNA but never both * 2nd outer one → Capsid * Major of Viruses are less or without Viral envelope or viral membranes (not necessary or extra) * Viruses without envelope → naked Viruses & Viruses with envelope → Enveloped viruses. * Virus in general composed from genetic material & Viral Coat (Capsid & May be envelope) ### 1- Virus Genome * Def.→ Giant thread like molecule composed of polymers of genes → each gene composed of smallest structural unit of virus genome called (nucleotides) | | | | ------------------ | -------------------------------------------------------------------------------------------------------------------------------------------------- | | A. Pentose sugar | Ribose → RNA Viruses -Deoxyribose →DNA Viruses | | B. Nitrogenous base | Purines - Has two rings 1. Adenine (A) 2. Guanine (G) Pyrimidines hexagonal ring 1. Thiamine (T) 2. Cytosine (C) 3. Uracil (U) | | C. Phosphate group | phosphoric acid present as charger or activator - nucleoside (un professional or nonfunctional or inactive nucleotide) as adenosine: pentose sugar & nitrogenous base → To activate it we add phosphorus → (nucleotide) or (professional or active or functional nucleotide) give negative charge to genome | ### Features & Criteria of Virus Genome | Comparison | DNA Viruses (Deoxyribonucleic acid) | RNA Viruses (Ribonucleic acid) | | --------------------- | ------------------------------------------------------------------------- | ------------------------------------------------ | | Types | Single type | mRNA, tRNA, rRNA | | Nitrogenous base | A&G&C & T | A&G&C & U | | Stability | Stable (low or no mutations) | Nonstable (highly mutable) | | Function | (information carrier) | Protein synthesis | | Examples | Adeno viruses, Herpes viruses, Pox viruses, Parvo viruses, Circo viruses (chicken anemia), Hepadna viruses, Polioma viruses, Asfa V. & Anello V. | Birna V, RetroV., Toga V., Orthomyxo V., Flavi V., buynia V., RhabdoV., BornaV. | | | | Reov., Calici V., Picorna V., Paramyxo V., corona V., arena V., AstroV. | | Strandness → Organization of configuration | | | ----------------------------------------- | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | single or double | 1. Double stranded: all DNA viruses except parvo, circo, Anello 2. Single stranded: all RNA viruses except reo, birna | | Segmentation | 1. Linear → All DNA viruses except Papova, Circo, Hepadna, Anello 2. Circular → Papova, Circo, Hepadna Arenav., Bunyav., Orthomyxov. All DNA viruses are non-segmented (monopartite) - All RNA viruses are non-segmented except → 1. Orthomyxo V. 6-8 segments 2. Bunya V. → 3 segments 3. Birna V. → 2 segments 4. Reo V. 10-12 segments 5. Arena V. 2-3 segments | | Copies of genomic genes | All viruses either DNA or RNA are haploid except → Retro V. (HIV) is diploid | | Polarity →not in ds Viruses | Positive sense (Sense) Act as mRNA → translated directly Not associated with RNA polymerase Don't contain enzymes Flavi v., Corona v., Retro v., ., Calici v., Picorna v Arteri v., Toga v. Astro v Negative sense (Antisense) Don't act as mRNA Associated with polymerase Contain enzymes Orthomyxo V. Bornav. Rhabado V. Ambisense + & - Arena V. Paramyxo V Buynia V Arena V. Anello & Parvo Circo V. | | Site of replication | | | -------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Intracytoplasmic | All DNA viruses except pox V. → Intracytoplasmic | | Intranuclear | All RNA viruses except Orthomyxo V. → Intranuclear | | Intranuclear & Intracytoplasmic | HIV → primary in cytoplasm but enter nucleus for some time then back to cytoplasm | | Function of V. genome | 1. Carry genetic information of V. 2.Redirect Cellular metabolic machinary toward Synthesis of Viral new organelles | * #Smallest genome in DNA Virus:- Chicken infectious anemia V. (Single strand) 1800 base =1.7-1.8 kb * #Smallest genome in RNA V.:- Hepatitis D V. → 1800 base =1.8 kb * #largest genome in DNA V.:- Pandora V. → 2.5m BP & Pox V. 135-350 Kbp * #largest genome in RNA V.:- Corona Virus 30.000 bp ## How the Virus Compress Its Genome?! | Strategy | | | ------------------------------------------ | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | **Strategy 1** Distribution of the virus genome on the both directions of the Double Stranded DNA Leading to → | when RNA Polymerase read strand (3`-5`) Produce Proteins Completely different from Proteins Produced when read the opposite Strand (5'-3') | | **Strategy 2** Over lapping of Viral genome (ORF) Open reading Fram = from start codon to stop codon -when RNA Polymerase start coding →begin from start codon but may be there is another start codon (ORF) → start coding again from that codon → result in over lapping EX → Hepatitis B Virus (Double stranded DNA V.) Its genome is Circular. | | **Strategy 3** → After transcription mRNA segments → cutting for smaller segments by mRNA Splicing → different and smaller protein occur in segment Influenza V. → Its genome segmented RNA Highest mutation Rate | | **Strategy 4** Translation Forms Very long Polypeptide chain. → virus use protease enzyme → cleavage of long polypeptide chain smaller protein Picorna V. | ## 2- Protein Coat (Viral Capsid & Viral Envelope) ### A) Viral Capsid * **Def.** * Structural Protein from genome of Virus itself * **Characters** * Formation from Capsomers arranged in Clusters by non Covalent hydrogen bonds. * Each Capsomer Composed of smallest Sub- units Called Protomers. * N.B→ Viral capsid is metastable → non-covalent binding (non-reversable) * Capsomer → morphological unit of Virus Capsid (Provide the Viral size and overall symmetry) * - Structural unit: Capsomeres & Structural Sub unit: Protomeres. * → Capsid may bind to nucleic acid to form nucleocapsid. * **Function** * • Genome protection → stable protective protein shell, recognizes specifically the viral genome, and packages it * • Assist in the envelopment process * • Fusion of the virion envelope to a cell membrane (for enveloped viruses) * • arrangement of the capsomeres around. * **Symmetry or Morphology** * Cubic, icosahedral, geometrical, polyhedral or isometric * icosahedral central axis → 12 corner, 30 edges, 20 triangular faces * • Rotational Axis: * 1- edges 2 folds (15 Axis) * 2- triangular face 3 folds (10 axis) * 3- corner (vertex) → 5 folds (6 axis) * Triangulation: * No. of Sub -Units present at each face. * • T1→60 Subunits(ideal) why? bonds between subunits are identical 100% around Central axis. * • T2 → 120 & * • T3 → 180 & * • T4-240 Quasi equivalence: * Capsids of more than 60 subunits → each subunit will place in a quasi equivalent position (hexamers will appear) * Non-covalent binding between subunits similar (not identical) * -Examples → * RNA Viruses → Picorna V, Flavi V * DNA Viruses → All are icosahedral except Pox V. * • Attachment of the virion to a host cell (for many viruses) * • Delivery of the genome to the appropriate site. * Helical (spiral, screw or tubular) * -Capsomers arranged spirally around Central axis. * Genome + capsid → nucleocapsid (Coil structure) * -Examples → * animal viruses * DNA Viruses → No * RNA viruses → all are spiral except Picorna V, Flavi V, Calci V& Retro V. * Complex symmetry * Dual symmetry Or binal or prolate symmetry Virus has both helical and icosahedral symmetry -Examples → Bacteriophage * neither icosahedral nor helical -Examples → * Pox v. → has 2 form and 2 envelopes and strange structure as lateral badies → shows ### B) Viral envelope / membranes * **Def.** * lipid bilayer derived from host cell by budding of nucleocapsid through cellular membrane for viruses can be the plasma membrane (HIV), nuclear membrane (HSV), Golgi (HSV), or the endoplasmic reticulum (HBV) but is virus-specific * **Site** * Cholesterol is a constituent of the viral membrane in viruses bud from plasma membrane, but not in the envelopes of viruses that bud from internal membranes * **Characters** * All DNA v. are naked (non-enveloped) except Poxviridae & Herpesviridae * Pox has 2 envelopes * All RNA V. are enveloped except Reoviridae & Flaviviridae & Orthomyxoviridae ### Components or layers | Layer | | | --------------------------------------------------- | ----------------------------------------------------------------------------------------------------------------------------------- | | 1- Inner matrix Protein (MP) beneath inner aspect of lipid bilayer link internal nucleocapsid to envelope from virus itself provide virion with its rigidity important role in the virus replication, assembly and maturation in all viruses except → Corona V., Bunya V. | 2- Middle Viral Envelope Encoded or synthesized by cell. barrier between MP And V.glycoproteins. Lipid bilayer surrounding capsid Release by budding through host cell. | | 3- Viral glycoproteins (spikes, peplomers, legends, arms, projection) From virus itself → protein from virus & CHO from cell Present in enveloped viruses -Structure → (1) an exterior head (2) transmembrane domain (3) anchor inserted in capsid or internal proteins or matrix protein Synthesized during budding or evagination of virus from the cell. May be perpendicular on envelope → S spike of corona May be parallel to envelope → E spikes of flaviviruses At least 2 functions → receptor binding & fusion -By one spike or two different spikes One spike for both functions G (uncleaved) of rabies HA (cleaved HA1&2) of influenza virus - S (cleaved S1&2)→ corona | ### Viruses either: * **1- enveloped** * Determine physical and chemical properties of virus → sensitive to lipid solvents as ether, chloroform so called heat labile or sensitive viruses * obtain its envelope via cytoplasmic membranes or via nuclear membrane or via Golgi apparatus or EPR * Enveloped viruses is more virulent than naked viruses. * **2-naked** * -resistant to lipid solvents. * -Determine or influence virus pathogenesity. ### Chemical structure of Virus | Component | Description | | --------------- | ---------------------------------------------- | | CHO | Virus coded present in viral glycoproteins (spikes) derived from host cell (unlike spike protein) | | Lipids | Cellular derived Form lipid bilayer - Only in enveloped viruses main component is phospholipid - envelope bud from plasma membrane that contains cholesterol while that of other viruses bud from internal membrane has not cholesterol | | Proteins | Virus & cellular coded - produced during infection and not incorporated into newly assembled virions essential for virus replication and assembly → modify and counteract host immune antiviral responses - have different enzymatic activities (viral enzymes) → 1. Enzymes involved in virus-cell interaction →HA, NA, F 2. Enzymes involved in replication → pol. & lig. 3. Enzymes provide mRNA transcription (viral transcriptases) (DNA or RNA dependent??) 4. Enzymes induce reverse transcription (RT) (DNA or RNA dependent??) 5. Enzymes with specific functions (IN) |