Medical Virology Lecture 1 PDF

Medical Virology: Lecture 1 Virus classification https://www.youtube.com/watch?v=HCFmr0H6VsE&list=PLGhmZX2NKiNlsqbNuq__7jeedNkdEaZBv Also Visit TWIV Website: http://www.twiv.tv/ 1 Objectives A...

Medical Virology: Lecture 1 Virus classification https://www.youtube.com/watch?v=HCFmr0H6VsE&list=PLGhmZX2NKiNlsqbNuq__7jeedNkdEaZBv Also Visit TWIV Website: http://www.twiv.tv/ 1 Objectives After completion of this session you should be able to define the following: Virus main properties Virus structure (more in details in the next lecture) Symmetry Classification Clinical classification Baltimore classification Compression between DNA & RNA viruses 2  What types of infectious agents do we have? Pathogenic organisms are of five main types: viruses, bacteria, fungi, protozoa, worms. AND…… !!! Prions misfolded protien spreads through meat 5:05 PM Medical virology 1 3 Notifiable diseases Medical virology 1 History The name virus, the Latin term for "poison" In 1892, Dimitri Ivanowsky demonstrated that the tobacco mosaic virus was a "filterable agent" of disease, since it could pass through a porcelain glass filter designed to trap very small bacterial cells. The filtrate of infected sap from tobacco leaves could pass the disease to healthy uninfected plants. Wendell Stanley isolated and characterized this virus in 1935 Small in size; 10- 300nm 400 Inert does not replicate by itself Filterable agent Infect all living organisms Medical virology 1 5  How do we classify viruses? LIFE Virus Classification How many kingdom do we have in life? Animals, Plants, Protists, Fungi, Archaebacteria, Eubacteria Isolates\Strains & based on what? 6 Characteristics Fundamentally, viruses are bundles of genetic material surrounded by a protein shell called a capsid. Four main properties : 1. Small size (Determined/Measured by…. 2. Shape (Capsid) 3. Genome (DNA or RNA) 4. Metabolically inert (obligate intracellular parasite) 7 What is a virus? Viruses are distinct biological entities with the following properties: cannot reproduce outside their host cell, 1. A virus is an infectious, obligate intracellular parasite. 2. The genetic material of a virus is either DNA or RNA. 3. The genetic material of a virus enters a host cell and directs the production of the building blocks of new virus particles (called virions). 4. New virions are made in the host cell by assembly of these building blocks. 5. The new virions produced in a host cell then transport the viral genetic material to another host cell or organism to carry out another round of infection.  Basic Components of the Virus The Virion: The complete infectious virus particle ❑ Protein coat / Capsid (Protect DNA/RNA; Antigenic properties) ❑ Capsomeres (may be more than one protein forming Capsomeres) proteins are more stable than phospholipid therefore nonenveloped viruses are more stable than enveloped viruses ❑ Nucleic acid Envelope protects the genetic material of the virus ,it allowa the virus to enter the host cell ❑ Envelope (What is the advantage?) made from phospjolipid of host memberane proteins for adhesion specific for certain cells by receptor binding domain 9 Budding Virion (x 555000)-EM resipiratory syncytial virus Envelope spikes (SH, G, & Infected hep-2 F) cell membrane Lipid layer (Matrix M, M2) Viral nucleocapsid Medical virology 1(N, P& L) 10  Virion Symmetry Symmetry refers to the way in which capsomere units are arranged in viral capsid. ENVELOP Virion has: 1. Icosahedral (cubic) Symmetry 2. Helical Symmetry 3. Complex structure https://www.ncbi.nlm.nih.gov/books/NBK8174/ Chapter 41Structure and Classification of Viruses  1. Icosahedral (cubical) Symmetry: An icosahedral is a polygon with 12 vertices (corner), 20 facet (sides) and 30 edges. Icosahedral capsid is the most stable and found in human pathogenic virus eg. Adenovirus, Picornavirus, Papovavirus, herpes virus etc. Icosahedral capsid are of two types; Pentagon: Pentagonal capsomere at the vertices Hexagon: Hexagonal capsomere at the vertices diff type of adenovirus cause diff disease (sore throat/gastric disease/ conjuctivities) https://www.onlinebiologynotes.com/virus-structure-symmetry/ 2. Helical Symmetry: The capsomere and nucleic acid are wined together to form helical or spiral tube like structure. Most of the helical viruses are enveloped and all are RNA viruses. i.e. Lipoprotein envelope surrounded The typical virus with helical symmetry is tobacco mosaic virus (TMV), which is a RNA virus with 2130 identical capsomeres arranged in a helix. influ retrovrius nzea Ex. Orthomyxoviruses, Paramyxoviruses, Retroviruses, Rhabdoviruses, Coronaviruses enveloped viruses are less stable cuz of the lipoplysacchride 3. Complex Structure: there is no specific set structure Large (300 nm), complicated structure Brick-shaped with core and lateral bodies, Env. Ex.Poxviruses (Small Pox, MPOX, Molluscum Contagiosum) Binal symmetry (Head and tail) icosahedral Medical virology 1 Virus Classification/Nomenclature Viruses are classified using a combination of characteristics, including the following: 1) Morphology: size, shape, presence of envelope, etc. 2) Physicochemical properties: thermal stability, detergent stability, molecular mass, etc. vriuses are classified based on their genmoic material (DNA/RNA long or short segmented or continous ss or ds 5’ to 3’ or 3’ to 5’) 3) Genome: size, type of nucleic acid, strandedness, etc. (uncluturable viruses). 4) Proteins: number, size, sequence, etc. 5) Lipids: content, character, etc. 6) Carbohydrates: content, character, etc. 7) Genome organization and replication: strategy of replication, number and position of open reading frames, transcriptional and translational strategies, site of virion assembly and release. 8) Antigenic properties: serological relationships. 9) Biological properties: Host range, mode of transmission, pathogenicity, tissue tropisms, geographic distribution, etc.  Classification order - family - subfamily - genus - species - type/subtype/strain In July 2013, the ICTV definition of species changed to state: "A species is a monophyletic group of viruses whose properties can be distinguished from those of other species by multiple criteria”. Viral morphology (not always) provides the basis for grouping viruses into families. Ex: Thus the name Picornaviridae is derived from pico (small) and RNA. family of virus (if we said with an ’n; we are tlaking about a Other examples: subtype) Astroviridae (astron means star); Arenaviridae (arena “sand”) describes the sandy/grainy appearance of the virion 18 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222810/ 1. What kind of genes/proteins are gastric used for classification? 2. Genotype vs phenotype? gentic material or morphology nose a family of small rna viruses http://www2.gsu.edu/~biotkf/bio475/475lecture3.htm  Classification At the moment classification is really only important from the level of families down. All families have the suffix viridae e.g. · Poxviridae · Herpesviridae · Parvoviridae · Retroviridae Subfamilies …….virinae Genera have the suffix virus. Within the Picornaviridae there are 5 genera: · enterovirus (alimentary tract) species e.g. poliovirus 1, 2, 3, EV68 · cardiovirus (neurotropic) species e.g. mengovirus · rhinovirus (nasopharyngeal region) species e.g. Rhinovirus 1a · apthovirus (cloven footed animals ) species e.g. FMDV-C · hepatovirus (liver) species e.g. Hepatitits A virus What is “STRAIN” and “Isolate”? 20  Clinical classification: DNA virus DNA viruses utilize the host machineray which is found in the nucleaus ( by that we mean polymerase and enzymes) Family Viruses Envelope Diseases Nucleic Polymerase or acid transcriptase present in the virion it has its own polymerase therefore it Poxvirus variola + smallpox DS DNA DNA dependent RNA pol replicates in the (+/-) cytoplasm Herpesviruses Herpes simplex + Herpes DS DNA Non (+/-) Vericella-zoster chickenpox adenoviruses adenoviruses _ Sorethroat DS DNA Non (+/-) Hepadnaviruses Hepatitis B + hepatits DS DNA RNA-Dependent DNA Pol (+/-) (RT) Papoviruses Papilloma virus _ warts DS DNA Non (+/-) parvoviruses B19 + Hemolytic SS DNA Non anemia (+/-) Viral polymerases play a central role in viral genome replication and transcription. Based on the genome type and the specific needs of particular virus, RNA-dependent RNA polymerase, RNA-dependent DNA polymerase, DNA-dependentRNA polymerase, and DNA-dependent RNA polymerases are found in various viruses. 21 Summary of key features of the DNA viruses Clinical classification: RNA virus RNA virus needs RNA dependant rna polymerase coronoavirus is the largest rna virus Family Viruses Envelope Diseases Nucleic Polymerase or transcriptase acid present in the virion Enteroviruses _ Paralysis SS (+) Non ? Picornaviruses , rhinoviruses colds Flaviviruses Hepatitis C, + Haemorrhagic SS (+) Non ? Yellow fever fever & dengue viruses Togaviruses rubivirus + rubella SS (+) Non ? Coronaviruses coronaviruses Respiratory inf. SS (+) Non ? Bunyaviruses Hanta viruses + Heamorrhagic SS (-) RNA-RNA fever (+ renal) Orthomyxoviruses influenza + influenza SS (-) RNA-RNA Paramyxoviruses RSV, measles + Respiratory SS (-) RNA-RNA &mumps infection, … Rhabdoviruses rabies + rabies SS (-) RNA-RNA Arenaviruses Lassa virus + meningitis SS (-) RNA-RNA Retroviruses HIV 1,2 + AIDS SS (+) RNA-DNA (RT) Reoviruses Rota virus _ gastroenteritis DS (-) RNA-RNA Filoviruses Ebola virus + Haemorrhagic SS (-) RNA-RNA fever Caliciviruses Norwalk + gastroenteritis SS (+) Non virus  RNA Viruses Classification 5:05 PM Medical virology 1 24 Virus Replication virus has spikes on its outer coat and they bind to the cell using the rceptor bindingvdomain and bind to the cell and enters the cell either it fuese and releases its genetic material or go through endocytosis the virus uitlizes the cell machneray to replicate the genomic material and to make proteins for itself Influenza Replication replicates in nuclueas because of its segmented genome  integration of the genetic material of HIV is what sets it apart from the influnzae  (1) DS DNA (+/-) (2) SS DNA (+) (3) DS RNA (+/-) Baltimore classification fragmented DS DNA transcription This classification is based on genetic contents and replication strategies of viruses transcription (1) DS DNA (+/-) (2) SS DNA (+) (3) DS RNA (+/-) transcription fragmented (1) DS DNA (+/-) (2) SS DNA (+) (3) DS RNA (+/-) fragmented DS DNA transcription mRNA DS DNA transcription transcription Genome acts as transcription mRNA transcription transcription transcription transcription mRNA DS DNA mRNA Genome acts as mRNA DNA/RNA (4) SS RNA (+) Genome acts(5) as SS RNA (-) transcription mRNA transcription transcription Reverse transcription DS DNA transcription DS DNA DNA/RNA (6) SS Retro RNA (+) (4) SS RNA (+) (5) SS RNA (-) DNA/RNA (4) SS RNA (+) (5) SS RNA (-) Reverse Diagram to show method of transcription of the different groups in the Baltimore transcription Reverse classification of virus genomes. Note: (+) = positive-sense RNA, i.e. acts as messenger; transcription (-) = negative-sense RNA, i.e. transcribed to form complementary-sense strands, which act as messenger. (6) SS Retro RNA (+) 29 (6) SS Retro RNA (+)  (1) DS DNA (+/-) (2) SS DNA (+) (3) DS RNA (+/-) Baltimore classification fragmented The Baltimore classification, developed by David Baltimore, is a virus classification system that viruses into families,DS groups transcription DNA depending on their type of genome (DNA, RNA, single-stranded (ss), double-stranded (ds), etc.) and their method of replication. transcription the mode of replication trascription of mrna (1) DS DNA (+/-) (2) SS DNA (+) (3) DS RNA (+/-) GROUP 4 ACTS AS MRNA AND mRNA is positive sense which means for positive sense has to become 3’ to 5’ to make mRNA fragmented transcription DS DNA transcription mRNA transcription Genome acts as transcription mRNA transcription transcription mRNA DS DNA Genome acts as mRNA DNA/RNA (4) SS RNA (+) (5) SS RNA (-) transcription transcription Reverse DS DNA transcription DNA/RNA (4) SS RNA (+) (5) SS RNA (-) (6) SS Retro RNA (+) Reverse sometimes grouo 4 acts as the mRNA and sometimes we have to make it 3/ to 5/ to make mRNA transcription Diagram to show method of transcription of the different groups in the Baltimore classification of virus genomes. Note: (+) = positive-sense RNA, i.e. acts as messenger; (-) = negative-sense RNA, i.e. transcribed to form complementary-sense strands, which act as messenger. (6) SS Retro RNA (+) 30 Adenoviridae Parvoviridae Reoviridae Picornaviridae Orthomyxoviridae retroviruses Hepadnaviridae 31 I: Double-stranded DNA (Adenoviruses; Herpesviruses; Poxviruses, etc) Some replicate in the nucleus e.g adenoviruses using cellular proteins. Poxviruses replicate in the Not important cytoplasm and make their own enzymes for nucleic acid replication. II: Single-stranded (+)sense DNA (Parvoviruses) Replication occurs in the nucleus, involving the formation of a (-)sense strand, which serves as a template for (+)strand RNA and DNA synthesis. III: Double-stranded RNA (Reoviruses; Birnaviruses) These viruses have segmented genomes. Each genome segment is transcribed separately to produce monocistronic mRNAs. IV: Single-stranded (+)sense RNA (Picornaviruses; Togaviruses, etc) a) Polycistronic mRNA e.g. Picornaviruses; Hepatitis A. Genome RNA = mRNA. Means naked RNA is infectious, no virion particle associated polymerase. Translation results in the formation of a polyprotein product, which is subsequently cleaved to form the mature proteins. b) Complex Transcription e.g. Togaviruses. Two or more rounds of translation are necessary to produce the genomic RNA. V: Single-stranded (-)sense RNA (Orthomyxoviruses, Rhabdoviruses, etc) Must have a virion particle RNA directed RNA polymerase. a) Segmented e.g. Orthomyxoviruses. First step in replication is transcription of the (-)sense RNA genome by the virion RNA-dependent RNA polymerase to produce monocistronic mRNAs, which also serve as the template for genome replication. b) Non-segmented e.g. Rhabdoviruses. Replication occurs as above and monocistronic mRNAs are produced. VI: Single-stranded (+)sense RNA with DNA intermediate in life-cycle (Retroviruses) Genome is (+)sense but unique among viruses in that it is DIPLOID, and does not serve as mRNA, but as a template for reverse transcription. VII: Double-stranded DNA with RNA intermediate (Hepadnaviruses) This group of viruses also relies on reverse transcription, but unlike the Retroviruses, this occurs inside the virus particle on maturation. On infection of a new cell, the first event to occur is repair of the gapped genome, followed by transcription 32 DNA Viruses RNA Viruses DNA is permanent RNA is short lived e.g. herpes infection e.g. influenza Replicate in nucleus, except poxvirus Replicate in cytoplasm, except retroviruses and orthomyxovirus Genomic is infectious (sufficient for Only +RNA virus genome is infectious replication) Use host RNA polymerase, except Must encode an RNA polymerase poxviruses Larger viruses encode DNA All (-) RNA viruses are enveloped and polymerase: adenovirus, herpes, carry polymerase poxvirus Segmented RNA viruses can change by reassortment of genome segments 33  Classification Summary 1. Type of Nucleic Acid 2. No. of strands of nucleic acid and physical construction/architecture 3. Genome polarity 4. Symmetry of nucleocapsid 5. Presence of absence of envelope. ……………………………………….. 34 6. Genetic and antigenic properties, virulence, tropism, etc.  Different maturation stages of RSV infectious cycle in hep2 cells (x 114,100). 5:05 PM Medical virology 1 35  iv. Virus leaving a cell by lyses or budding (x 11,124). Budding Lyses 5:05 PM Medical virology 1 36 Video resource: By David baltimor – important clip: http://www.youtube.com/watch?v=tqZmALbccOo http://www.courses.fas.harvard.edu/~biotext/animations/viralinfection.html http://bio-alive.com/categories/virology/virology.htm 37 Thank you for your attention Reference and reading recommendations: 1. Your text book: part 1, Virology, how it all began, Page 4 2. www.cdc.gov( Centers for Disease Control and Prevention) https://www.ncbi.nlm.nih.gov/books/NBK8174/ (important) ASMA Altani 38