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Medical Virology: by ORIBA DAN LANGOYA

Medical Virology: by ORIBA DAN LANGOYA



Basic introduction with details....on virology

Basic introduction with details....on virology



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    Medical Virology: by ORIBA DAN LANGOYA Medical Virology: by ORIBA DAN LANGOYA Presentation Transcript

    • By ORIBA DAN LANGOYAMBchBMakerere University College of HealthScience
    •  Viruses are complexes consisting of protein and anRNA or DNA genome. They lack both cellular structure and independentmetabolic processes. They replicate solely by exploiting living cells basedon the information in the viral genomeVIRUS
    •  Size 25nm (picornavirus) to 250 Genome DNA or RNA . Double-stranded or single-stranded nucleic acid, Depending on the species. Structure Viruses arecomplexes comprising virus-coded protein and Nucleic acid; ie DNA or RNA Reproduction Only in living cell Antibiotics; Viruses are unaffected by antibiotics, butcan be inhibited by interferon and certainchemotherapeutic agents.General x-tics of Viruses
    •  A mature virus particle is also known as a virion.Consist of 3 basic components A genome Capsid EnvelopeMorphology andStructure
    • Viral structureNucleocapsidEnveloped virusDNARNAor
    •  Fig:Capsid symmetryIcosahedral HelicalNaked capsidEnvelopedLipidGlycoproteinMatrix
    • Myovirus and influenzavirus
    •  Genome: DNA or RNA genome as well asconfiguration of nucleic acid structure: single-stranded (ss) or double-s (ds);RNA viruses arefurther sub classified according to plus and minuspolarity Capsid symmetry: cubic, helical, or complexsymmetry. Presence or absence of an envelope. Diameter of the virion, or of the nucleocapsid withhelical symmetry.Classification
    •  The steps are: Adsorption of the virus to specific receptors on the cellsurface. Penetration by the virus and intracellular release ofnucleic acid. Proliferation of the viral components: virus-codedsynthesis of capsid and non capsid proteins, replication ofnucleic acid by viral and cellular enzymes. Assembly of replicated nucleic acid and new capsidprotein. Release of virus progeny from the cell.Replication
    • Viral replication
    •  Adsorption. Virus particles can only infect cellspossessing surface “receptors” specific to theparticular virus species.eg CD4: receptor for HIV;ICAM-1: receptor for rhinoviruses, the complement(C3) receptor that is also the receptor for the Epstein-Barr virus, Penetration and uncoating. Viruses adsorbed to thecell surface receptors then penetrate into the cell bymeans of pinocytosis (a process also known asviropexis).Explanations
    •  Production of viral mRNA. In a DNA virus infection,cellular polymerases transcribe mRNA in the nucleus of thehost cell from one or both DNA strands, where by the RNA is processed (splicing, poly adenylation,)as with cellular mRNA . An exception to this procedure isthe poxviruses, which use their Own enzymes to replicate inthe cytoplasm.Viral Protein Synthesis
    •  In viruses with antisense-strand ss RNA and ds RNAthe transcription of the genomic RNA into mRNA iscarried out by the viral polymerases, usually with-out further processing of the transcript. In sense-strand ss RNA viruses, the genome canfunction directly as mRNA . Arena viruses, are classified as “ambisense viruses.”Part of their genome codes in antisense (–), anotherpart in sense (+) polarity.Continuation of viralreplication
    •  Segmented genomes. A separate nucleic acid segment ispresent for each protein example: reoviruses mRNA splicing. The correct mRNA is cut out of theprimary transcript (as in the cell the exon is cut out ofthe hnRNA) (examples: adenoviruses, retroviruses… “Early” and “late” translation. The different mRNAmolecules required for assembly of so-called early andlate proteins are produced at different times in theinfection cycle, possibly from different strands of viralDNA (examples, papovaviruses, herpesviruses)Protein Synthesis Control
    •  Post-translational control. This process involvesproteolytic cutting of the primary translationproduct into functional subunits. Viral proteasesthat recognize specific amino acid sequences areresponsible for this, e.g., the two poliovirus proteasescut between glutamine and glycine or tyrosine andglycine. Such proteases, some of which have been documented in radiocrystallographic images, are potential targets forantiviral chemotherapeutics (example: HIV).Protein synthesiscontinuation
    •  The release of viral progeny in some cases correlatesclosely with viral maturation, where by envelopes orcomponents of them are acquired when the particles“bud off” of the cytoplasmic membrane and areexpelled from the cell In non enveloped viruses, release of viral progeny isrealized either by means of lysis of the infected cellor more or less continuous exocytosis of the viralparticlesRelease
    •  The process of releaseIs from A through B to CRelease of Retrovirusesfrom an Infected Cell
    •  viral genetic material is subject to change bymutation. Lack of a corrective replication “proofreading”mechanism results in a very high incidence ofspontaneous mutations in RNA viruses increasing the genotypic variability within eachspecies (“viral quasispecies”). potential for genetic material is also inherent in thereplication process.Genetics
    •  Mutations are changes in the base sequence of anucleic acid, resulting in a more or less radicalalteration of the resulting protein Medically important are mutants with weakenedvirulence that have retained their antigenicity andreplication capabilities intact. These are known as “attenuated” viruses. They arethe raw material of live vaccines.Mutation
    •  The viral replication process includes production of alarge number of copies of the viral nucleic acid. strand breakage and reunion will lead to newcombinations of nucleic acid segments or ex-changesof genome segments (influenza), so that the geneticmaterial is redistributed among the viral strains(recombination). Genetic material can also b e ex-changed betweenvirus and host cell by insertion of all, or part, of theviral genome into the cell genome.Recombination
    • Viruses as VectorsNongenetic Interactions In mixed infections variousviral components can beexchanged or they maycomplement (or interferewith) each other’s functions(phenotype mixing,complementation orinterference). Such processes do not resultinstable heritability of newx-ticsPhenotypic mixing the genome of virus A isintegrated in the capsid ofvirus B, or a capsid made up ofcomponents from two(closely related) virustypes is assembled andthe genome of one of the“parents” is integrate d init.
    • Viruses as Vectors Phenotypic interference; theprimary infecting virus(usuallyavirulent) may inhibit thereplication of a second virus, orthe inhibition may be mutual. The interference mechanism maybe due to interferon productionor to a metabolic change in thehost cell. “Quasispecies. ” When viralRNA replicates, there is no“proofreading” mechanism tocheck for copying errors as inDNA replication. The result isthat the rate of mutations in RNAviruses is about 10 to power 4. Complementation; infectingviral species have geneticdefects that renderreplication impossible. The “partner” viruscompensates for the defect,by supplying the missingsubstances or functions inhelper effect. In this way, adefective and non defectivevirus, or two defectiveviruses, can complement each other.Eg: murine sarcoma viruses
    • Possible consequences of viral infection for the host cell: Cytocidal infection (necrosis) Apoptosis Noncytocidal infection: cell destruction is bysecondary means. Eg immunological response Latent infection: no viral replication or cell death Tumor transformation: change host cells into CancerHost-Cell Reactions
    •  Cell death occurs eventually after initial infect ionwith many viral species. Virus production coupled with cell destruction istermed the “lytic viral life cycle. whether necrotic or apoptotic is there as on (alongwith immunological phenomena) for the diseasemanifested in the macro organism Structural changes leading to necrosis ApoptosisCell Destruction (CytocidalInfection, Necrosis)
    •  Factors that contribute to the origins anddevelopment of a disease. In the case of viruses, theinfection is by a parenteral or mucosal route. The viruses either replicate at the portal of entry only( local infection) or reach their target organhematogenously, lympogenously or by neurogenicspread (generalized infection).Pathogenesis
    •  Viruses can be transmitted horizontally (within agroup of individuals) vertically (from mother to offspring). Verticalinfection is either transovarial or by infection of thevirus in utero (ascending or diaplacental). Connatal infection is the term used when offspringare born infectedTransmission
    • Mode oftransmissionExamplesDirect transmission– fecal-oral (smear infection)– aerogenic (dropletinfection)– intimate contact (mucosa)Indirect transmission– alimentary– arthropod vector s– parenteralEnterovirusesInfluenza virusesHerpes simplex virusHepatitis A virusYellow fev er virusHepatitis B virusHorizontal Transmission ofPathogenic Viruses
    •  mucosa of the respiratory and gastrointestinal tracts. Intact epidermis presents a barrier to viruses, whichcan, however , be overcome through Micro-traumataor mechanical inoculation (e.g., bloodsuckingarthropods)Portal of entry
    •  Local infection: the viruses spread only from cell to cell. The infection andmanifest disease are thus restricted to the tissues in theimmediate vicinity of the portal of entry. Example: rhinoviruses that reproduce only in the cells of the upperrespiratory tract. Generalized infection: Viruses usually replicate then disseminated via the lymphducts or bloodstream and reach their target organ eitherdirectly or after infecting another organ. Eg: EnterovirusViral dissemination in theorganism
    •  Viral prophylaxis is by use of active vaccines Vaccines containing inactivated viruses generallyprovide shorter lived and weaker protection thanlive vaccines. Passive immunization with human immunoglobulinis only used in a small number of cases, usually aspost exposure prophylaxis.Prevention
    •  Immune prophylaxis: induction of immunity is themost important factor in prevention of Viralinfection Chemoprophylaxis: administration ofchemotherapeutic agents when an infection isexpected instead of after it has been diagnosed toblock viral metabolism Exposure prophylaxis: designed to prevent thespread of pathogens in specific situations.Value of the differentmethods
    •  Inhibitors of certain steps in viral replication can beused as chemo-therapeutic agents to treat viralinfections. In practical terms, it is much more important toinhibit the synthesis of viral nucleic acid than of viralproteins. The main obstacles involved are the low level ofspecificity of the agents in some cases (toxic effectsbecause cellular metabolism is also affected) and thenecessity of commencing therapy very early in theinfection cycleChemotherapy
    • ChemotherapeuticagentEffect/indication Adamantanamin (amantadine) Acycloguanosine (acyclovir, Zovirax) Dihydropropoxymethylguanosine(DHPG, ganciclovir, Cymevene) Ribavirin Nucleoside RT inhibitors (NRTI) Phosphonoformate (foscarnet) Protease inhibitors Neuraminidase inhibitors Antisense RNA Inhibition of uncoating in influenzaviruses Inhibition of DNA synthesis in HSV andVZV Inhibition of DNA synthesis in CMV Inhibition of mRNA synthesis andcapping Infections with Lassa virus andperhaps in severe paramyxovirus andmyxovirus infections Inhibition of RT in HIV Inhibition of DNA synthesis inherpesviruses, HIV, HBV Inhibition of viral maturation in HIV Inhibition of release of influenza viruses Complementary to viral mRNA, whichit blocks by means of hybridization(duplexing)
    •  Virus isolation: by growing the pathogen in acompatible host ; usually done in cell cultures, rarelyin experimental animals or hen embryos. Direct virus detection: The methods of serology,molecular biology, and Electron microscopy are usedto identify viruses or virus components directly i.e.without preculturing, in diagnostic specimens. Serodiagnostics: involving assay of antiviralantibodies of the IgG or IgM classes in patient serum.Laboratory Diagnosis