Virology and Human Disease

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Virology and Human Disease

• Tuesday, August 12

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Viruses

• Infectious agents found in virtually all life
  forms including humans, animals, plants, insects,
  and bacteria
• Virion Structure
• genetic material (either DNA or RNA, double or
  single stranded, linear or circular)
• Protein coat (capsid) surrounding genetic
  material
• Rod (helical), polyheldral, or more complex
• with or without a lipid envelope
• Viruses are not free living
• Unable to reproduce themselves outside of a
  living cell
• Transmit their genetic information from one cell
  to another
• Viruses often damage or kill the cells that they
  infect

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Figure 18.1 Size of a virus, a bacterium, and a
eukaryotic cell
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Figure 18.2 Viral structure
Rod-shaped
Icosohedral
Enveloped
Complex
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Figure 18.3 A simplified viral reproductive cycle

• Obligate intracellular parasites
• Rely on the equipment of cell to replicate
• Host range viruses can only infect certain cell
  types
• Dependant on recognition of host cell receptor
• Entry, uncoating, replication, release, cell
  lysis, infection of new cells

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Bacterial Viruses

• Bacteriophages phages
• Virulent phage
• Reproduces only by a lytic life cycle
• Lytic results in the lysis of the host cell
• Phage T4 (infects E. coli)
• Temperate phage
• Reproduce by either lytic or lysogenic life cycle
• Lysogenic - replication does not destroy host
• Phage ? (infects E. coli)

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Figure 18.4 The lytic cycle of phage T4
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Figure 18.02x2 Phages
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Figure 18.5 The lysogenic and lytic reproductive
cycles of phage ?, a temperate phage
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Animal Viruses

• Virus Classification
• Genome
• DNA or RNA (/- sense)
• Size (kb)
• Single or double stranded, linear or circular
• segments, sequence
• Morphology
• Virion size and shape
• Plus or minus envelope
• Capsid symmetry and structure
• Protein
• Biological properties
• Physical and chemical properties

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Table 18.1 Classes of Animal Viruses, Grouped by
Type of Nucleic Acid
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Figure 18.6 The reproductive cycle of an
enveloped virus

• Glycoproteins on envelope recognize receptor on
  host cell
• Viral envelope fuses with cell membrane
• Genome and capsid enter the cell
• Genome is copied
• New RNA genomes
• mRNA translated into capsid proteins and
  glycoproteins for envelope
• Capsid assembly
• Virus buds from cell

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Viral Entry receptors and fusion

• Initial attachment binding to host cell
• Viral surface protein recognizes receptor
• Carbohydrates
• Lipids
• Proteins transmembrane
• Entry virion conformational change in response
  to receptor or pH
• Location of entry
• Plasma membrane (neutral pH)
• Endosomal membrane (acidic pH)
• Type of entry
• Fusion enveloped viruses
• Penetration nonenveloped viruses

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Modification of Host Cell Function

• Effects on cellular translation
• Viruses activate PKR (cellular kinase) which
  suppresses cellular translation
• Effects through receptor binding
• Viral receptor binding may mimic the effects of
  the natural ligand
• Induction of cell proliferation
• Viruses need replication machinery and induce
  cells to enter the cell cycle upon infection
• Effects on cellular RNA processing
• Inhibit cellular transcription
• Degrade cellular mRNAs
• Alter RNA processing or export

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Viral Replication

• DNA viruses
• Replicated and transcribed similar to host cell
• Examples adenovirus, herpes virus
• RNA viruses
• Plus stranded
• Translated directly (therefore RNA is infectious)
• Virally encoded RNA-dependant RNA polymerase
  (RdRp) synthesizes more genomic RNA and mRNA for
  proteins
• Example poliovirus
• Minus stranded
• Must be transcribed by RdRp for replication and
  transcription of viral mRNA
• Enzyme is carried by the virus into the cell
  during infection
• Example influenza, measles
• Retroviruses HIV

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Figure 18.02x1 Adenovirus
Virus infects the upper respiratory tract (common
cold) and GI tract (diarrhea)
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Figure 18.x6 Herpes

• 8 herpesviruses infect humans
• Human diseases
• Oropharyngeal and genital lesions herpes
  simplex
• Chickenpox varicella zoster virus
• Congenital microcephaly CMV (growth
  retardation)
• Burkitts lymphoma EBV (childhood tumor)
  (mononucleosis)
• Kaposis sarcoma KSHV

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Viral Replication

• DNA viruses
• Replicated and transcribed similar to host cell
• Examples adenovirus, herpes virus
• RNA viruses
• Plus stranded
• Translated directly (therefore RNA is infectious)
• Virally encoded RNA-dependant RNA polymerase
  (RdRp) synthesizes more genomic RNA and mRNA for
  proteins
• Example poliovirus
• Minus stranded
• Must be transcribed by RdRp for replication and
  transcription of viral mRNA
• Enzyme is carried by the virus into the cell
  during infection
• Example influenza, measles
• Retroviruses HIV

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Figure 18.x3 Paralytic Polio

• Summer time epidemic disease summer of 1885 in
  England
• More than 20,000 cases each year in the U.S.
• Infection spreads to brain and CNS and replicates
  in muscle cells, spreading to motor neurons and
  causing paralysis
• Poliovirus was cultured Robbins, Enders, and
  Weller received the Nobel Prize in 1954
• First vaccine developed in 1955 by Salk was
  inactivated virus
• Live attenuated vaccine (Sabin) was approved in
  1961 and eliminated virus from the Americas

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Viral Replication

• DNA viruses
• Replicated and transcribed similar to host cell
• Examples adenovirus, herpes virus
• RNA viruses
• Plus stranded
• Translated directly (therefore RNA is infectious)
• Virally encoded RNA-dependant RNA polymerase
  (RdRp) synthesizes more genomic RNA and mRNA for
  proteins
• Example poliovirus
• Minus stranded
• Must be transcribed by RdRp for replication and
  transcription of viral mRNA
• Enzyme is carried by the virus into the cell
  during infection
• Example influenza, measles
• Retroviruses HIV

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Influenza

• Worldwide epidemics (pandemics) have been
  documented for over 100 years.
• Pandemic of 1918 resulted in over 20 million
  deaths
• The virus was finally isolated in 1933
• Highly contagious, acute respiratory illness
• Occurs seasonally (mid-Dec March)
• Virus replicates in epithelium of the upper and
  lower respiratory tract
• Effective vaccines contain antigens from all 3
  different strains of influenza

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Figure 18.x5 Influenza epidemic
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Measles

• Measles virus initially replicates in the
  respiratory tract and then disseminates to other
  organs producing disease
• Symptoms include fever, malaise, anorexia,
  conjunctivitis, and oral rash that spreads from
  the face to the extremities (broad red patches
  with little bumps)
• Important cause of blindness in children
• There is an effective vaccine there are still
  epidemics worldwide

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Figure 18.x2 Measles
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Difficulties with Anti-Viral Therapy

• Large number of variant viruses can cause the
  same disease (quasispecies)
• Large numbers of progeny (burst size 10,000)
• Rapid replication short life cycle
• High mutation rate
• genomes are copied with much less accuracy
• Lack repair systems to correct errors
• Inability of drugs to disable a virus without
  disabling healthy cells
• Development of anti-viral agents is a major focus
  of current research

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Vaccines

• Preventing certain viral illnesses by inducing
  immunolic memory
• Inoculation of healthy individuals
• Live attenuated vaccines mutant, less virulent
• Inactivated (killed) vaccines eliminate
  infectivity
• Purified viral components (subunits)
• Virus eradication
• Virus must have no alternative hosts
• Vaccination must produce lifelong immunity

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Figure 18.x1 Smallpox

• In the 20th century, over 300 million succumbed
  to this disease
• First disease to be eradicated by human
  intervention

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Emerging Viruses

• Processes contributing to the emergence of new
  viral diseases
• Mutation of existing viruses
• Spread of existing viruses from one host species
  to another
• Dissemination of a viral disease from a small,
  isolated population
• Emerging viruses result from the expansion of
  existing viruses to new host species by mutation,
  dissemination, and evolution

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Figure 18.8 Emerging viruses Ebola virus

• Ebola virus (filovirus, ss(-)RNA, enveloped)
• Initially recognized in Africa in 1976
• Hemorrhagic fever highly lethal (25-90
  fatality)
• Vomiting, massive bleeding, circulatory collapse,
  shock
• Emerged from human contact with unknown host in
  Africa
• Infections cluster because disease progression is
  so rapid it limits the time it can be spread

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Figure 18.8 Emerging viruses Hantavirus

• Hantavirus (bunyavirus, ssRNA, enveloped)
• In 1993 an epidemic of highly lethal infectious
  disease occur in the Four Corners area
• Flu-like symptoms, pulmonary disorder, death
• Common in deer mice, which increased in
  population in 1993 after a wet season increased
  the food supply
• Humans acquired the virus when then inhaled dust
  with traces of urine and feces from infected mice

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Figure 18.9 Viral infection of plants

• Stunt plant growth and diminish crop yields

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Figure 18.10 A hypothesis to explain how prions
propagate
Simpler infectious agents - Prions

• Infectious proteins causing degenerative brain
  diseases
• Scrapie in sheep
• Mad cow disease in cows
• Creutzfeldt-Jakob disease in humans
• Prions are misfolded forms of normal proteins in
  the brain
• Prions induce normal proteins to convert to prion
  form triggering a chain reaction that increases
  their numbers