Chapter 6 - Virology                               - Viruses have a host range.
That
                                                          is, viruses infect specific cells or
• Topics                                                  tissues of specific hosts, or specific
  – Structure                                             bacteria, or specific plants.
  – Classification
  – Multiplication
  – Cultivation and replication                           - Viral specificity refers to the specific
  – Nonviral infectious agent                             kinds of cells a virus can infect. It is
                                                          regulated by the specificities of
  – Teratogenic/Oncogenic
                                                          attachment, penetration and
                                                          replication of the virus (Receptors)
Properties of viruses                                   A virion is an infectious virus particle - not all virus
- Viruses are not cells, do not have nuclei or          particles are infectious
mitochondria or ribosomes or other cellular             Viruses are composed of a nucleic acid, RNA or DNA
components.                                             - never both.
- Viruses replicate or multiply. Viruses do not grow.   - All viruses have a protein coat (capside) or shell
- Viruses replicate or multiply only within living      that surrounds and protects the nucleic acid core.
cells.                                                  - Some viruses have a lipid envelope or membrane
- Viruses are obligate intracellular parasites.         surrounding a nucleocapsid core. The source of the
                                                        envelope is from the membranes of the host cell.
- The term virus was coined by Pasteur, and is
from the Latin word for poison.                         - Some viruses package enzymes - e.g. RNA-
                                                        dependent-RNA polymerase or other enzymes -
Components of viruses -                                 some do not package enzymes
                                                                  Size comparison of viruses -
                                                                       how big are they?
                 Structure
•   Size and morphology
•   Capsid
•   Envelope
•   Complex
•   Nucleic acid
                                                        Mycoplasma?
                                                                                                                   1
There are two major structures of viruses
called the naked nucleocapsid virus and
the enveloped virus
                                                              Capsid
                                                • Protective outer shell that
                                                  surrounds viral nucleic acid
                                                • Composed of capsomer subunits
                                                  - collectively protect the nucleic
                                                  acid from the environment
                                                • Capsid spikes - used for binding
                                                  to cell surface proteins
   NAKED                    Enveloped
                                                          Nucleic acid
               Envelope
                                               • Viruses contain either DNA or RNA
  • Lipid and proteins - basically a
                                               • Possess only the genes to invade
    modified version of our
                                                 and regulate the metabolic activity
    membranes
                                                 of host cells
  • Envelope spikes - bind to cell
                                               • Ex. Hepatitis B (4 genes) and
    surface proteins
                                                 herpesviruses (100 genes)
  • During release of animal viruses,
                                               • No viral metabolic genes, as the
    a part of the host membrane is
                                                 virus uses the host’s metabolic
    taken
                                                 resources
           Bacteriophages
• Bacteriophage
  – Polyhedral head
  – Helical tail
  – Fibers for attachment
• Are considered either LYTIC or
  TEMPERATE
• Are often associated with virulence
  genes in bacteria
     - EX. - diphtheria toxin in Clostridium
  diphtheriae - also Botulinum toxin from
  C. botulinum
                                                                                       2
                                            T-even bacteriophage penetrate the host cell
     Growth curve for a bacteriophage       by specifically binding and injecting their DNA
                                            into the host cell
After replication, bacteriophage release
lysozyme, weaken/destroy/rupture cell and
release numerous virions
                                            Temperate phages can cause disease
                                            For example, Corynebacterium diphtheriae and
                                            Clostridium botulinum contain prophages that
                                            have genes which encode for toxins
                                            Without these prophages, they DO NOT
                                            produce the toxin – without toxin, no disease
                                            Thus, they are examples of bacteria and
                                            viruses interacting to cause medically relevant
                                            disease
             Plaque Assay
                                                                                              3
 Temperate phage - formation of a
 prophage and LYSOGENY
                                                                                                  Classification
                                                                                       • Host Range
                                                                                       • Envelope or Naked virus
                                                                                       • Type of disease
                                                                                       • Baltimore Classification of
                                                                                         Viruses (4 major groups)
                                                                                           – + vs - sense
                                                        PROPHAGE
        Baltimore Classification of Animal Viruses
 Class VII ds/ss DNA               Class I ds DNA (+/-)                                      General Steps in Viral
                                   Poxviridae
 Hepadnaviridae
                                   Herpesviridae                                                Multiplication
                                   Papovaviridae         Class II ss DNA (+ or -)
                                   Adenoviridae          Parvoviridae
                                                                                       •   Adsorption
Class VI ss RNA (+)
Retroviridae                 RNA                                                       •   Penetration
                                   mRNA (+)                   Class III ds RNA (+/-)
               DNA                                            Reoviridae               •   Uncoating
                                                                                       •   Synthesis
          Class V ss RNA (-)                 Class IV ss RNA (+)
          Paramyxoviridae
          Orthomyxoviridae
                                             Picornaviridae                            •   Assembly
          Rhabdoviridae                      Togaviridae
          Filoviridae
                                             Flavivirida
                                             Coronaviridae
                                                                                       •   Release
          Bunyaviridae
                                             Caliciviridae
          Arenaviridae
                                             Astroviridae
       Viruses recognize
       specific receptors
       Figure 6.12 and then
       the virus penetrates the
       cell Figure 6.13
                                                                                                                       4
                                          Endocytosis
        Membrane Fusion
                                    Animal Virus
                                    Replication
                               General replication scheme for an
      General Steps in Viral   animal virus
         Multiplication
•   Adsorption
•   Penetration
•   Uncoating
•   Synthesis
•   Assembly
•   Release
                                                                   5
  A Magnified View of Viral Budding -
  ENVELOPED VIRUSES
                                         Worst case
                                         scenario -
                                         HIV virions
                                         exiting from
                                         a T cell
                                        Most simple -
                 Fig. i6.2a             and efficient   Fig. i6.2b
What                                    case = ss+
happens if it                           RNA virus
is a dsDNA
virus???                                Examples:
                                        Coronavirus
Examples:
Herpes virus                            RETROVIRUS
Gift of life!!
                                          Replication of RNA viruses
                                          Insight 6.2 - Note differences
                                          between + sense, - sense and
                                          retrovirus replication
                                          Also, be able to compare -contrast
                                          phage and animal virus replication
                                                                               6
                                                      Fig. 6.16 Cytopathic changes in cells and cell
           Cytopathic effects                         cultures infected by viruses
  • Damage to the host cell due to a
    viral infection
    –Transformation
                                                      Syncytia – multinucleated cells        Inclusion bodies
                                                                      Tight Junction Disruption
Viral transformation of cells – Oncogenic viruses
dsDNA viruses (Papillomavirus, EBV, Hep B)                 Cultivation and Replication
                                                          • In vivo methods
                                                             – Laboratory animals
                                                             – Embryonic bird tissues
                                                          • In vitro methods
                                                             – Cell or tissue culture
                                                           Making the Influenza vaccine
Cultivation of animal viruses –
It is possible to study viruses in animals, but due
to the complexity of the animal, expense of
animals and the political environment relative to
the use of animals, alternatives have been
developed.
Chick embryos in eggs - influenza
Persistent infection – transformation/cancer
                                                                                                                7
A monolayer of monkey kidney cells is a cell
culture enabling the propagating viruses.                   Noncellular Infectious
                                                                   Agents
                                                                     • Prions
                                                   Protein structure of the two forms of the prion protein
  Prions – Stanley Pruisner –                            GOOD!!!!                      BAD!!!
  Nobel Prize in Medicine: 1978
  Prions are proteinaceous infectious
  agents - Prions do not have nucleic
  acid.
  Prions are considered to be the
  causative agents of Creutzfeld Jakob
  disease, scrapie, bovine spongiform
  encephalopathy (BSE) and kuru.
 Oncogenic potential of viruses -                  At least six viruses have been found to cause
                                                   human cancer - Epstein-Barr virus, hepatitis B
 Cancer is a set of diseases known to disturb      virus, hepatitis C virus, human papilloma virus
 the normal functioning and properties of cells.   (HPV-8, HPV-16), HTLV-I (adult T-cell
                                                   leukemia and lymphoma), HTLV-II (hairy cell
 Tumors may be malignant or benign -
 malignant tumors spread by metastasis.            leukemia),
 Peyton Rous in 1911 discovered that a             Oncogenes are normal cellular regulatory
 filterable agent could transmit a sarcoma (a      genes. When modified, these genes code for
 type of cancer) in chickens - Rous sarcoma        gene products that disturb the normal
 virus - the first retrovirus described.           regulatory patterns of cells and can result in a
                                                   loss of the normal properties of cell growth and
                                                   division resulting in “cancer”.
                                                                                                             8
Viral oncogenes are found usually in
retroviruses.                           Malignant
                                        tumor
Viral oncogenes are viral homologs of   formation
the cellular oncogenes.
Viral oncogenes can disturb normal
regulatory properties by certain
mechanisms.