Virology by ORIBA DAN LANGOYA

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VIROLOGY

• By ORIBA DAN LANGOYA
• MBchB II
• Makerere University College of Health Science

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VIRUS

• Viruses are complexes consisting of protein and
  an RNA or DNA genome.
• They lack both cellular structure and independent
  metabolic processes.
• They replicate solely by exploiting living cells
  based on the information in the viral genome

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General x-tics of Viruses

• Size 25nm (picornavirus) to 250
• Genome DNA or RNA . Double-stranded or
  single-stranded nucleic acid,
• Depending on the species. Structure Viruses are
  complexes comprising virus-coded protein and
• Nucleic acid ie DNA or RNA
• Reproduction Only in living cell
• Antibiotics Viruses are unaffected by
  antibiotics, but can be inhibited by interferon
  and certain chemotherapeutic agents.

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Morphology and Structure

• A mature virus particle is also known as a
  virion. Consist of 3 basic components
• A genome
• Capsid
• Envelope

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Viral structure
Enveloped virus
Nucleocapsid
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Capsid symmetry

• Fig

Icosahedral
Helical
Naked capsid
Enveloped
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Myovirus and influenza virus
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Classification

• Genome DNA or RNA genome as well as
  configuration of nucleic acid structure
  single-stranded (ss) or double-s (ds)RNA viruses
  are further sub classified according to plus and
  minus polarity
• Capsid symmetry cubic, helical, or complex
  symmetry.
• Presence or absence of an envelope.
• Diameter of the virion, or of the nucleocapsid
  with helical symmetry.

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Replication

• The steps are
• Adsorption of the virus to specific receptors on
  the cell surface.
• Penetration by the virus and intracellular
  release of nucleic acid.
• Proliferation of the viral components
  virus-coded synthesis of capsid and non capsid
  proteins, replication of nucleic acid by viral
  and cellular enzymes.
• Assembly of replicated nucleic acid and new
  capsid protein.
• Release of virus progeny from the cell.

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Viral replication
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Explanations

• Adsorption. Virus particles can only infect cells
  possessing surface receptors specific to the
  particular 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
  the cell surface receptors then penetrate into
  the cell by means of pinocytosis (a process also
  known as viropexis).

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Viral Protein Synthesis

• Production of viral mRNA. In a DNA virus
  infection, cellular polymerases transcribe mRNA
  in the nucleus of the host 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 is the poxviruses,
  which use their Own enzymes to replicate in the
  cytoplasm.

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Continuation of viral replication

• In viruses with antisense-strand ss RNA and ds
  RNA the transcription of the genomic RNA into
  mRNA is carried out by the viral polymerases,
  usually with-out further processing of the
  transcript.
• In sense-strand ss RNA viruses, the genome can
  function directly as mRNA .
• Arena viruses, are classified as ambisense
  viruses. Part of their genome codes in antisense
  (), another part in sense () polarity.

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Protein Synthesis Control

• Segmented genomes. A separate nucleic acid
  segment is present for each protein example
  reoviruses
• mRNA splicing. The correct mRNA is cut out of the
  primary transcript (as in the cell the exon is
  cut out of the hnRNA) (examples adenoviruses,
  retroviruses
• Early and late translation. The different
  mRNA molecules required for assembly of so-called
  early and late proteins are produced at different
  times in the infection cycle, possibly from
  different strands of viral DNA (examples,
  papovaviruses, herpesviruses)

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Protein synthesis continuation

• Post-translational control. This process involves
  proteolytic cutting of the primary translation
  product into functional subunits. Viral
  proteases that recognize specific amino acid
  sequences are responsible for this, e.g., the two
  poliovirus proteases cut between glutamine and
  glycine or tyrosine and glycine. Such proteases,
  some of
• which have been documented in radio
  crystallographic images, are potential targets
  for antiviral chemotherapeutics (example HIV).

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Release

• The release of viral progeny in some cases
  correlates closely with viral maturation, where
  by envelopes or components of them are acquired
  when the particles bud off of the cytoplasmic
  membrane and are expelled from the cell
• In non enveloped viruses, release of viral
  progeny is realized either by means of lysis of
  the infected cell or more or less continuous
  exocytosis of the viral particles

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Release of Retroviruses from an Infected Cell

• The process of release
• Is from A through B to C

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Genetics

• viral genetic material is subject to change by
  mutation.
• Lack of a corrective replication proofreading
  mechanism results in a very high incidence of
  spontaneous mutations in RNA viruses
• increasing the genotypic variability within each
  species (viral quasispecies).
• potential for genetic material is also inherent
  in the replication process.

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Mutation

• Mutations are changes in the base sequence of a
  nucleic acid, resulting in a more or less radical
  alteration of the resulting protein
• Medically important are mutants with weakened
  virulence that have retained their antigenicity
  and replication capabilities intact.
• These are known as attenuated viruses. They
  are the raw material of live vaccines.

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Recombination

• The viral replication process includes production
  of a large number of copies of the viral nucleic
  acid.
• strand breakage and reunion will lead to new
  combinations of nucleic acid segments or
  ex-changes of genome segments (influenza), so
  that the genetic material is redistributed among
  the viral strains (recombination).
• Genetic material can also b e ex-changed between
  virus and host cell by insertion of all, or part,
  of the viral genome into the cell genome.

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Viruses as Vectors

• Nongenetic Interactions

• Phenotypic mixing

• the genome of virus A is integrated in the capsid
  of virus B,
• or a capsid made up of components from two
  (closely related) virus types is assembled and
  the genome of one of the parents is integrate d
  in it.

• In mixed infections various viral components can
  be exchanged or they may complement (or interfere
  with) each others functions (phenotype mixing,
  complementation or interference).
• Such processes do not result instable
  heritability of new x-tics

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Viruses as Vectors

• Phenotypic interference the primary infecting
  virus(usually avirulent) may inhibit the
  replication of a second virus, or the inhibition
  may be mutual.
• The interference mechanism may be due to
  interferon production or to a metabolic change
  in the host cell.
• Quasispecies. When viral RNA replicates,
  there is no proofreading mechanism to check for
  copying errors as in DNA replication. The result
  is that the rate of mutations in RNA viruses is
  about 10 to power 4.

• Complementation infecting viral species have
  genetic defects that render replication
  impossible.
• The partner virus compensates for the defect,
  by supplying the missing substances or functions
  in helper effect. In this way, a defective and
  non defective virus, or two defective viruses,
• can complement each other. Eg murine sarcoma
  viruses

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Host-Cell Reactions

• Possible consequences of viral infection for the
  host cell
• Cytocidal infection (necrosis)
• Apoptosis
• Noncytocidal infection cell destruction is by
  secondary means. Eg immunological response
• Latent infection no viral replication or cell
  death
• Tumor transformation change host cells into
  Cancer

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Cell Destruction (Cytocidal Infection, Necrosis)

• Cell death occurs eventually after initial infect
  ion with many viral species.
• Virus production coupled with cell destruction is
  termed the lytic viral life cycle.
• whether necrotic or apoptotic is there as on
  (along with immunological phenomena) for the
  disease manifested in the macro organism
• Structural changes leading to necrosis
• Apoptosis

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Pathogenesis

• Factors that contribute to the origins and
  development of a disease. In the case of viruses,
  the infection is by a parenteral or mucosal
  route.
• The viruses either replicate at the portal of
  entry only ( local infection) or reach their
  target organ hematogenously, lympogenously or by
  neurogenic spread (generalized infection).

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Transmission

• Viruses can be transmitted horizontally (within a
  group of individuals)
• vertically (from mother to offspring). Vertical
  infection is either transovarial or by infection
  of the virus in utero (ascending or
  diaplacental).
• Connatal infection is the term used when
  offspring are born infected

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Horizontal Transmission of Pathogenic Viruses
Mode of transmission Examples
Direct transmission fecal-oral (smear infection) aerogenic (droplet infection) intimate contact (mucosa) Indirect transmission alimentary arthropod vector s parenteral Enteroviruses Influenza viruses Herpes simplex virus Hepatitis A virus Yellow fev er virus Hepatitis B virus
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Portal of entry

• mucosa of the respiratory and gastrointestinal
  tracts.
• Intact epidermis presents a barrier to viruses,
  which can, however , be overcome through
  Micro-traumata or mechanical inoculation (e.g.,
  bloodsucking arthropods)

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Viral dissemination in the organism

• Local infection
• the viruses spread only from cell to cell. The
  infection and manifest disease are thus
  restricted to the tissues in the immediate
  vicinity of the portal of entry. Example rhino
  viruses that reproduce only in the cells of the
  upper respiratory tract.
• Generalized infection
• Viruses usually replicate then disseminated via
  the lymph ducts or bloodstream and reach their
  target organ either directly or after infecting
  another organ. Eg Enterovirus

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Prevention

• Viral prophylaxis is by use of active vaccines
• Vaccines containing inactivated viruses generally
  provide shorter lived and weaker protection than
  live vaccines.
• Passive immunization with human immunoglobulin is
  only used in a small number of cases, usually as
  post exposure prophylaxis.

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Value of the different methods

• Immune prophylaxis induction of immunity is the
  most important factor in prevention of Viral
  infection
• Chemoprophylaxis administration of
  chemotherapeutic agents when an infection is
  expected instead of after it has been diagnosed
  to block viral metabolism
• Exposure prophylaxis designed to prevent the
  spread of pathogens in specific situations.

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Chemotherapy

• Inhibitors of certain steps in viral replication
  can be used as chemo-therapeutic agents to treat
  viral infections.
• In practical terms, it is much more important to
  inhibit the synthesis of viral nucleic acid than
  of viral proteins.
• The main obstacles involved are the low level of
  specificity of the agents in some cases (toxic
  effects because cellular metabolism is also
  affected) and the necessity of commencing therapy
  very early in the infection cycle

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Chemotherapeutic agent Effect/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 influenza viruses Inhibition of DNA synthesis in HSV and VZV Inhibition of DNA synthesis in CMV Inhibition of mRNA synthesis and capping Infections with Lassa virus and perhaps in severe paramyxovirus and myxovirus infections Inhibition of RT in HIV Inhibition of DNA synthesis in herpesviruses, HIV, HBV Inhibition of viral maturation in HIV Inhibition of release of influenza viruses Complementary to viral mRNA, which it blocks by means of hybridization (duplexing)
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Laboratory Diagnosis

• Virus isolation by growing the pathogen in a
  compatible host usually done in cell cultures,
  rarely in experimental animals or hen embryos.
• Direct virus detection The methods of serology,
  molecular biology, and Electron microscopy are
  used to identify viruses or virus components
  directly i.e. without preculturing, in diagnostic
  specimens.
• Serodiagnostics involving assay of antiviral
  antibodies of the IgG or IgM classes in patient
  serum.

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THANKS FOR YOUR TIME