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					  “TRANSPOSONS ALL GROWED UP”
(…OR IS IT THE OTHER WAY AROUND…)
UNIFYING FEATURES OF LIFE
Composed of cell(s)
Require energy
Possess genetic material
Reproduction
Evolution (characteristic of population)
Etc.
          VIRUSES
Share some of the unifying features of life
Differ from “normal” life in some of these
characteristics
Are viruses alive?
              VIRUSES
CELLULAR LIFE              VIRUSES
 Composed of cell(s)         Not cellular
 Require energy              Only when infecting
 Genetic material (DNA)      DNA or RNA
 Reproduction                Only within host
 Evolution (populations)     Very rapid evolution
 Etc.
      VIRUS STRUCTURE
SIMPLEST VIRUSES
     “naked viruses”
     “naked nucleocapsid”
 Genetic material
     DNA or RNA
     Single- or double-stranded
 Protein coat
     “capsid”
     Surrounds nucleic acid
       VIRAL GENOME
DNA or RNA                             Relatively few genes
Single-stranded or                         Viruses: 3 - hundreds
double-stranded                            E. coli: ~ 4,000
Linear or circular                         H. sapiens: ~40,000

Single or multiple pieces              Lacks genes for many
                                       essential functions
Relatively small
                                           Must “borrow” this
   Capsid has finite size                  machinery from host cells
   Packed very tight
       Up to 10X pressure of champagne bottle
          VIRAL CAPSID
Composed of many identical protein subunits
   “capsomeres”
Determines viral shape
   Isometric / icosahedral
   Helical
   (Some more complex)
Attachment proteins
   “Spikes”
   Attach virus to host cell
Nucleic acid + capsid =
nucleocapsid
 BACTERIOPHAGES
“Phage”
Virus infecting bacteria
Most are naked viruses
Most have complex shape
      VIRUS STRUCTURE
ENVELOPED VIRUSES
 Genetic material
 Protein coat
 Envelope
     Phospholipid bilayer
     External to nucleocapsid
     Integral proteins
     Possesses attachment
      proteins
         “Spikes”
         Attach virus to host cell
     Matrix protein often inside
      envelope
     VIRUS STRUCTURE
ADDITIONAL COMPONENTS
 Genetic material
 Protein coat
 Envelope
 Enzymes
    Present in some viruses
    Encoded by virus
    Required for viral life cycle
    Not available in host
    e.g., integrase
    e.g., RNA-dependent RNA polymerase
    e.g., RNA-dependent DNA polymerase (reverse transcriptase)
  SIZE   SIZE    SIZE SIZE        SIZE
HOW      SMALL   IS SMALL?
 Most microorganisms are
 small
 Viruses are among the
 smallest “microorganisms”
    10 nm – 500 nm range
    100 – 1,000 times smaller
     than the cells they infect
    Frequently not removed by
     filter sterilization
VIRAL REPLICATION CYCLE
Viruses cannot reproduce themselves without
assistance
   Lack machinery for energy
    harvesting, protein synthesis, etc.
   Must “borrow” this machinery from
    host cells
   “Obligate intracellular parasites”
VIRAL REPLICATION CYCLE
Viral reproduction requires infection of host cells
   Viral genetic material is introduced into host cell
   Host cell is reprogrammed
   Host cell produces many copies of the infecting virus




                             
VIRAL REPLICATION CYCLE

Orderly series of steps
   Attachment (Adsorption)
   Penetration (Entry)
   Replication
   Assembly & Maturation
   Release
 VIRAL REPLICATION CYCLE
ATTACHMENT
 “Adsorption”
 Virus binds to host cell
      Viral surface proteins bind
       to cell surface receptors
          Different viruses require
          different receptors
          Different host cells possess
          different receptors
      Why would a cell possess
       receptors for a virus?
VIRAL HOST RANGE
The “host range” of a
particular virus includes all
cell types able to be infected
   These cells possess receptors to
    which the virus is specific
   e.g., certain species
   e.g., certain strains of a
    particular species
   e.g., certain cell types within a
    multicellular organism
VIRAL REPLICATION CYCLE
ENTRY
 “Penetration”
 Viral genetic material
 enters cell
      Various mechanisms
      Portions of the virus may
       remain outside of host cell
 VIRAL REPLICATION CYCLE
PRODUCTION OF VIRAL COMPONENTS
 Various mechanisms
 Detailed further in specific life cycles

ASSEMBLY & RELEASE
 Various mechanisms
 Detailed further in specific life cycles
VIRUS - HOST INTERACTIONS
Host metabolism completely taken over
    “Lytic” infection
Host metabolism partially taken over
    (No specific name for this)
“Peaceful coexistence” with host cell
    “Lysogenic” infection
    Latent infection
    Accomplished by “temperate” phages
     T4: LYTIC LIFE CYCLE
ATTACHMENT
  Proteins on phage tail attach to receptors on E. coli cell wall
PENETRATION
  Lysozyme on tip of phage tail degrades portion of cell wall
  Phage DNA injected through cell wall
  Passes through cytoplasmic membrane (unknown mechanism)
  Protein coat remains outside of cell
      T4: LYTIC LIFE CYCLE
REPLICATION           Phage proteins include
 DNA  mRNA  protein  Proteins sealing punctured
     Uses host components       cell wall
                                Enzymes for phage DNA
                                 synthesis
                                Nuclease that degrades host
                                 DNA
                                    Complete takeover of host
                                    cell metabolism
                                Capsid and other structural
                                 proteins
                                Enzymes weakening cell
                                 wall to facilitate release
     T4: LYTIC LIFE CYCLE
ASSEMBLY
 Most newly produced phage parts spontaneously
 assemble into bacteriophages
     T4: LYTIC LIFE CYCLE
RELEASE
 Host cell packed with phage particles  lyses
 Promoted by viral lysozyme produced late in cycle
 Burst size: ~200 phage per cell within ~30 minutes
T4: LYTIC LIFE CYCLE
    OTHER LYTIC PHAGES
Single-stranded RNA phages MS2 and Qb
   Infect F+ strains of E. coli
   Explain this specificity
   Burst size: ~10,000
   Encodes an RNA-dependent RNA polymerase
Single-stranded DNA phage fX174
Double-stranded DNA phage l (lambda)
   Either lytic or lysogenic
  l: LYTIC VS. LYSOGENIC
ATTACHMENT & PENETRATION
 Similar to T4
LYTIC LIFE CYCLE         LYSOGENIC LIFE CYCLE
  DNA  mRNA  protein     Injected DNA inserted into host
     lysis              chromosome
                               “provirus” or “prophage”
                               Most viral genes not expressed
                               Phage are not produced
                               Prophage replicates with host
                                   Exponential increase in number
     l: LYSOGENIC CYCLE
Integration of DNA into
bacterial chromosome
   Site-specific recombination
       Short homologous segments
       between phage and host
       Always integrates at same
       site
   Reversible
       Spontaneous excision
       ~1/10,000 divisions
       Activation of SOS repair
       guarantees excision
l: LYTIC VS. LYSOGENIC
                 LYSOGENS
Characteristics of cells possessing a provirus
   Immune to infections by same type of phage
      Proviral protein binds to & inactivates infecting virus
   New genes  new properties
      Corynebacterium diptheriae + b prophage  diptheria
      toxin  diptheria
      Clostridium botulinum + prophage  toxin  botulism
      Streptococcus pyogenes + prophage  toxin  scarlet
      fever
      TRANSDUCTION
Generalized transduction
   Bacterial DNA erroneously
    packaged inside capsid
   Infects new host
   Bacterial DNA transferred
       Any gene
   Facilitated by virulent (lytic) and
    temperate (lysogenic) phages
TRANSDUCTION
  Specialized transduction
     Imperfect prophage excision
      removes some host DNA
     Packaged into capsid
     “defective phage”
     Infects new host
     Bacterial DNA transferred
         Genes near integration site
     Facilitated by temperate
      phages only
PROTECTION FROM PHAGES
RESTRICTION-MODIFICATION SYSTEM
 Two adjacent genes
    Restriction enzyme
       Recognizes and cleaves specific DNA sequence
       e.g., GAATTC
    Modification enzyme
       Modifies host DNA to prevent cleavage
       Methylation of residues within target sequence
 Viral DNA is unmodified, is recognized as
 foreign, and is cleaved and inactivated
 Restriction enzymes allow us to easily
 manipulate DNA
PART II
ANIMAL VIRUS CLASSIFICATION
Inherently difficult, changing
Based mainly on
    Genome structure
    Virus particle structure
    Presence or absence of an envelope
Reflects evolutionary relationships
ANIMAL VIRUS CLASSIFICATION
Divided into families
    14 RNA-virus families infect vertebrates
    7 DNA-containing families infect vertebrates
    “-viridae”
Members of families share common ancestor
    Relationship between families more complex
Families further subdivided into genera
ANIMAL VIRUS CLASSIFICATION
Family
    “-viridae”
Genus
    “-virus”
Species
    Named for disease caused
    e.g., polio  poliovirus
Types
    Akin to subspecies, strains, etc.
    Some types should be separate species
Binomial nomenclature not used
ANIMAL VIRUS GROUPINGS
Non-evolutionary groupings
e.g., Transmission route between individuals
   Enteric viruses
   Respiratory viruses
   Zoonoses
   Sexually transmitted viruses
          ENTERIC VIRUSES
Ingested on fecal-contaminated material
   “Fecal-oral route”
Often cause gastroenteritis
   Inflammation of stomach and intestine
Some cause systemic disease rather than
gastroenteritis
   e.g., poliovirus
    RESPIRATORY VIRUSES
Inhaled, replicate in respiratory tract
Remain localized in respiratory tract
   e.g., rhinovirus
Inhaled viruses causing systemic diseases not
included
   e.g., mumps virus, measles virus
                   ZOONOSES
Transmitted from one animal species to another
(including humans)
e.g., rabies
   e.g., bat  Old Yeller  humans
   (humans cannot transmit to other humans)
e.g., canine distemper
   e.g., dogs  lions
e.g., arboviruses
   Arthropod borne viruses (“bugs” are arthropods )
   Infect arthropods, replicate, transmitted to vertebrates
   e.g., West Nile Virus
SEXUALLY TRANSMITTED VIRUSES

Transmitted during sexual activity
Many cause lesions in genital tract
   e.g., herpesviruses, papillomaviruses
Some cause systemic infections
   e.g., HIV, hepatitis viruses
          METHODS OF STUDY
CULTIVATION OF HOST CELLS
 Multiplication only inside host cells
     Living animals
     Embryonated chicken eggs
     Cell culture (tissue culture)
        Limited life span
        Immortal cells from tumor
        METHODS OF STUDY
VIRAL QUANTIFICATION
  Plaque assay
  (Electron) microscopic counting
  Quantal assays
  Hemagglutination
        METHODS OF STUDY
VIRAL QUANTIFICATION
 Plaque assay
    Known volume of virus-containing solution added to
     tissue culture cells
    Each plaque represents one virion
       Similar to CFUs in bacteria
 (Electron) microscopic counting
    Can often distinguish between infective and non-
     infective virions
    Helpful in identifying type of virus
          METHODS OF STUDY
VIRAL QUANTIFICATION
  Quantal assays
     Several dilutions administered to cells
     Dilution at which 50% of host cells are infected is determined
         ID50 (infective dose) or LD50 (lethal dose)
 Hemagglutination
     Some viruses agglutinate (clump) red blood cells
         e.g., influenza virus
     Serial dilutions of virus added to RBCs
     Highest dilution showing maximal hemagglutination
      determined
HOST - VIRUS INTERACTIONS
Bacteriophage host organism is single cell
    Possess rudimentary defense mechanisms
Animal virus host organism is multicellular
    Possesses various defense mechanisms
    Immunity can exist
Virus – host coevolution
    Host  more resistant
    Virus  less pathogenic
    “balanced pathogenicity”
        “Normal” host is often asymptomatic
        Disease results when transmitted to a susceptible host
             e.g., measles & smallpox in New World indigenous populations
    ACUTE INFECTIONS
Short duration
Host may develop immunity
Life cycle similar to that of virulent phage
   Attachment
   Entry
   Targeting
   Uncoating
   Replication
   Maturation
   Release
   Shedding
   Transmission
    ACUTE INFECTIONS
Attachment
   Similar to bacteriophages
Entry
   Different mechanisms for naked vs. enveloped
Targeting
   Virion targeted to site where it will multiply
   e.g., most DNA viruses multiply in nucleus
Uncoating
   Nucleic acid separates from protein coat
    ACUTE INFECTIONS
Replication of proteins
   Utilizes host cell ribosomes and other machinery
Replication of nucleic acid
   Genetic material
    varies between families
   Methods of nucleic acid
    replication variable
   NA replication often
    involves viral enzymes
    ACUTE INFECTIONS
Maturation
   Assembly of virions
   Multistep process
Release
   May involve lysis or budding
Shedding
   Virions exit host
   Generally use same opening or
    surfaces used to gain entry
Transmission
   Transmitted to new host
PERSISTENT INFECTIONS
Viruses continually present in the body
Released by budding
May or may not cause disease
   Can be transmitted to others
Four categories
   Late complications following acute infection
   Latent infections
   Chronic infections
   Slow infections
   (Some overlap in these categories)
PERSISTENT INFECTIONS
Latent infections
   Acute infection  symptomless period 
    reactivation
   Infectious virions undetectable until reactivation
   Initial vs. reactivated symptoms may differ
   e.g., herpesviruses (HSV-1, HSV-II, varicella)
   Sometimes involves integration into host DNA
PERSISTENT INFECTIONS
Chronic infections
   Infectious virus detectable at all times
   Disease may be either present or absent over
    extended period of time
   e.g., Hepatitis B virus
Slow infections
   Amount of virus gradually increases over long
    periods of time
   Asymptomatic over long periods of time
   e.g., lentiviruses (HIV, etc.)
                      TUMORS
Result from abnormal growth of cells
   “transformed cells”
Control of cell division / differentiation altered
   Tumor suppressor gene  inactivated form
   Proto-oncogene  oncogene
   Oncogenes carried by some viruses
   Proto-oncogenes activated by some viruses
Types of tumors
   Benign tumor remains in defined area
   Malignant tumor spreads to other parts of body
       “metastasis”
       “cancer”
        VIRAL HOST RANGE
Includes all cell types able to be infected
   e.g., species, strains, cell types within a species
   These cells possess receptors recognized by virus
Host range can be altered
   Phenotypic mixing
   Genetic reassortment
    PHENOTYPIC MIXING
Animal cells sometimes
simultaneously infected by two
different viruses
   Host ranges overlap, but differ
Viral genetic material and viral
capsids mismatched
Host range temporarily altered
   Can facilitate interspecies gene
    transfer
GENETIC REASSORTMENT
Some viruses possess segmented genomes
   e.g., influenza virus
Many strains of these viruses exist
   Host ranges overlap, but differ
Two different strains can infect a single cell
   e.g., bird and human viruses can both infect pigs
RNA segments mixed and matched
   “antigenic shift”
   New strain avoids immunity already in place
          PLANT VIRUSES
Many plant diseases are
caused by viruses
   Especially prevalent in
    perennial plants
   Yield can be severely reduced
   Without plants (food), we are
    dead
Infection sometimes
desirable
   e.g., color variegation in tulips
         PLANT VIRUSES
Enter via wound sites, not via receptors
Source of virus
   Soil
   Vectors (insect, human, etc.)
   Tobacco
Virus-resistant crops genetically engineered
                  PRIONS
Proteinaceous infectious agents
Protein only, no nucleic acid
Linked to diseases of humans and other animals
   e.g., mad cow disease, kuru, scrapie, etc.
   “transmissible spongiform encephalopathies”
   Slow, always fatal
Prion converts normal host protein into prion
                   VIROIDS
Infectious single-stranded RNA
   246 – 375 nucleotides long
   ~10% of size of smallest known RNA virus
   Replicate autonomously
   Circular, resistant to digestion by nucleases
   Cause disease
      Mechanism unknown
   All identified viroids infect plants

				
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posted:11/10/2011
language:English
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