Why do we need to study Viruses and bacteria

1
CHAPTER 18 THE GENETICS OF VIRUSES AND BACTERIA

• Why do we need to study Viruses and bacteria?
• 1. Viruses and bacteria are the simplest
  biological systems
• 2. Thus it is easy to study lifes fundamental
  molecular mechanisms in their most basic,
  accessible forms .
• 3. unique genetic features help us for
  understanding diseases that they cause.

2

• Bacteria
• Small and simple in comparison to eukaryotes
• Bacteria are prokaryotic organisms
• Bacteria can be parasites, free living, or
  symbiotic.
• Size comparison

• Viruses
• are smaller than bacteria
• Viruses are considered as living entity.
• Viruses are made of nucleic acid enclosed in a
  protein coat
• Viruses are obligatory parasites to their host
  cell.

3
Unique Features of Viruses

• Viruses are not cells.
• Non-living no metabolism, do not respond to
  stimuli,
• They infectious particles.
• Require electron microscope to visualize viruses
  small!
• Structure
• A. nucleic acid
• B. protein coat or capsid,
• C. (some cases) membranous envelope.

Or RNA
4
Viral genetic material, or genome, vary in their
chemical composition, size and shape

• DNA or RNA
• double-stranded DNA or single-stranded DNA,
• double-stranded RNA, or single-stranded RNA,
• linear or circular molecule of nucleic acid.
• genomes vary in size with just four genes to
  several hundred genes.

Genome
5
(No Transcript)
6
Viral shapes
7

• Envelopes
• Some viruses have membranes covering their
  capsids.
• These envelopes are derived from the membrane of
  the host cell.

8

• Host range
• Some viruses (like the rabies virus) have a host
  range to infect several species
• others infect only a single species.
• Most viruses of eukaryotes attack specific
  tissues.
• Eg) Human cold viruses infect only cells lining
  the upper respiratory tract.
• The HIV binds only to certain white blood cells.
• Poliomyelitis infects nerve cells.

Rabies
HIV
9

• Viruses identify host cells by like an enzyme
  identifies its substrate using lock-and-key fit
• Viral capsomere proteins bind to specific
  receptor on the hosts cell membrane.
• Receptor mediated entry!

10
How do Viruses reproduce?

• Remember, viruses are not capable of reproducing
  by themselves! They are obligate intracellular
  parasites.
• Phages have two kinds of life cycles

LYTIC CYCLE
LYSOGENIC CYCLE
11

• LYTIC CYCLE
• In the lytic cycle, the phage reproductive cycle
  results in the death of the host cell.
• The host cell lyses (breaks open) and releases
  the phages produced by it.
• The viruses that reproduce by lytic cycle are
  called virulent phages

12

• Lytic Cycle
• Virus attaches to host cell with the help of
  receptor
• Virus introduces its genetic material (DNA/RNA)
  into the host cell
• Leaves its protein coat outside
• Host cell shuts down its machinery and begins
  obeying orders from viral genetic material

START
END
13
Viral genome uses host cells machinery

• The host cell begins to transcribe/
• translate viral genome

14

• 1). The genetic material is copied several times
• 2). Use cell machinery to make capsomere (capsule
  proteins)
• 3) Capsomeres assemble around the genetic
  material to form viruses
• 4) Host cell is filled with fully assembled viral
  particles
• 5) Host cell bursts and releases more viruses
• 6) These released viruses are ready to infect new
  host cells

15

• LYSOGENIC CYCLE
• Viral DNA enters host cell
• Viral DNA, instead of using cell machinery right
  away, becomes part of the host DNA!
• The virus at this time is called a prophage

16

• When ever host divides, it viral DNA is copied
  and passed on to daughter host cell.
• Now there are several host cells that have viral
  DNA

O
O
O
O
17
Lysogenic cycle to lytic cycle

• The prophage lies dormant in host cells genome
  until something triggers the prophage to leave
  genome and begin to replicate. Eg) UV radiation
• The virus then enters the lytic cycle.

18
(No Transcript)
19
Non-phage viruses can use different ways to enter
host and multiply
HIV
20

• Influenza virus
• Has envelope over its capsid
• derived from host cell
• virus attaches to host cell receptor using the
  glycoprotein of the envelope
• Envelope introduces viral DNA enclosed in capsid
  into host cell

21
Viral InfectionEntire virus enters cell,
uncoats releases genome into cell
1
2
4
3
22

• As in the lytic cycle, viral genome multiplies
  using hosts proteins, enzymes, and nucleotides.
• Self-assembly of the virus takes place
• Virus is budded off the host by covering the
  capsule with the host plasma membrane
• Host cell membrane becomes envelope
• Host cell is not damaged

23

• HIV is a Retrovirus
• Infects T4 lymphocytes (white blood cells)
• have the most complicated life cycles.
• Their genome is made of RNA.
• HIV also has an enzyme called reverse
  transcriptase

24

• Reverse transcriptase converts (reverse
  transcribes) RNA to DNA template.
• The newly made DNA is inserted into host cell
  chromosome . It is called as a provirus
• The hosts RNA polymerase transcribes the viral
  DNA into more RNA molecules.

Reverse transcription!
25
Link between viral infection symptoms

• Viruses can directly lyse cell, kills cell.
• Triggering the release of hydrolytic enzymes from
  lysosomes toxic to cell-kills it.
• Make the host cell produce toxins that lead to
  disease symptoms in body.
• Some viruses have toxic molecules on them, such
  as envelope proteins.

Extent of Damage Some cells can be repaired
(respiratory epithelium after a cold) Some
infections cause permanent damage if cells cannot
be repaired or replaced. (nerve cells after
poliovirus infection).
26
Vaccines

• Immune system recognizes certain molecules on the
  surface of viruses or on the surface of cells
  infected by viruses.
• Our immune system attacks these cells, kills them
  and remembers this molecule.
• Vaccines are
• 1) Attenuated virus (live, non-virulent form
  Sabin)
• Mimics actual virus and stimulate the immune
  system to fight virus from future infections
• 2) Dead virus particles (Salk).

27
Influenza Virus

• 2 types of influenza virus A, B
• 2 kinds of antigens on surface of virus
• Neuraminidase (N) Hemaglutinin (H)
• There are 15 different H subtypes
• There are 9 different N subtypes

28
Flu Vaccine

• There are three different strains in a flu
  vaccine
• Antigenic drift produces new virus strains that
  may not be recognized by the body's immune
  system, happens continuously(why you can get flu
  more than once a year)
• Antigenic shift abrupt, major change in
  influenza A virus, creates a new subtype. People
  have little or no protection against new subtype.
• May cause a flu pandemic..1918 Spanish Flu est.
  20 million people died. Ongoing monitoring 1957
  Asian Flu, 1968 Hong Kong Flu 1976, 1977 Russian
  Flu scare, 1997 Avian Flu

29

• There are anti-viral drugs that target specific
  points of a virus life cycle.

30
Virus and Cancer

• Some viral infections are linked to cancer.
• eg) Hepatitis B linked to liver cancer
• Papilloma virus linked to cervical cancer
• HTLV-1 linked to adult leukemia
• Why?
• Some viral genes are oncogenes or turn on our
  cells natural proto-oncogenic genes (like genes
  necessary for cell cycle)

31
How did they evolve? Not understood at this point

• Viruses are considered as the transition state
  between life and non-life.
• biologically inert outside host cell
• Active in a host cell reproduce
• Thus they are called obligate parasites.

32
Other pathogenic molecules

• Viroid tiny pieces of circular RNA molecules
  that infect plants.
• RNA molecules can affect metabolism of plant and
  affect growth.

33
Prions

• An infective misfolded protein.
• It can induce other correctly folded proteins to
  change shape into the incorrect form.
• Misfolded proteins build up in brain, form
  plaques and destroys nerve cells.

34
Bacteria
35
The Genetics of Bacteria

• Bacteria are prokaryotes
• Reproduce by binary fission
• Achieve variation by three methods
  transformation, transduction and conjugation

36
Bacteria are Prokaryotes

• Single cell
• No true membrane bound nucleus.
• Cell has cell membrane that encloses the
  cytoplasm
• Cell membrane is surrounded by cell wall
• Cell wall is made of amino sugar called as
  peptidoglycan

37
Bacteria Structure

• 1) Cell wall composition
• Gram positive (purple)
• Gram negative (pink)
• 2) Cell Shape
• Cocci or round
• Bacillus or rod shaped
• Spirillum or spiral

38

• Cytoplasm enclosed the genetic material that is
• is one double-stranded, circular DNA molecule.
• In E.coli, DNA is 4.6 million nucleotide pairs
  with about 4,300 genes.
• This is 100 times more DNA than in a typical
  virus
• and 1,000 times less than in a typical eukaryote
  cell.

39
Bacterial genetic information
In addition to the chromosomal DNA of the
nucleoid, bacteria have small circular
molecules of DNA outside the nucleoid
region called plasmids.
40
Reproduction

• Bacteria normally reproduce by binary fission
• clones of the original bacteria
• BUT! In order to adapt to the surrounding
  environmental conditions,
• bacteria recombine their genetic material by
  three different methods.
• Thus generating diversity in the bacterial
  population
• In eukaryotes, this problem is overcome by
  meiosis

41

• The three methods by which bacteria acquire
  variation are
• Transformation
• Transduction
• Conjugation

42

• Transformation
• Bacteria can take up naked, foreign DNA from the
  surrounding environment. This process is called
  transformation.

43
Transformation

• Bacterial cells have areas on their membranes
  that will recognize foreign DNA and take it in.

44

• Transduction
• Bacterial genome gets recombined when a phage
  carries bacterial genes from
• one bacterial host cell to another.
• This is of two types general and specialized

45

• Conjugation
• also known as bacterial sexual reproduction
• transfer of genetic material between two
  bacterial cells that are temporarily joined.
• One cell (male) donates DNA and its mate
  (female) receives the genes.
• A sex pili from the male initially joins the two
  cells and creates a cytoplasmic bridge between
  cells.

46

• The F plasmid (F factor) consists of about 25
  genes, most required for the production of sex
  pili.
• (F is for fertility)
• Cells with F plasmid are called F and they
  pass this condition to their offspring.
• Cells lacking either form of the F factor, F-,
  and they function as DNA recipients.

47

• Male bacteria transfers the F plasmid from male
  to female bacteria.
• Plasmid is small, circular, self-replicating DNA
  that contains a few genes.
• Plasmids are not critical to life of bacteria,
  but contain beneficial genes.

48

• The plasmid form of the F factor can become
  integrated into the bacterial chromosome.
• Now, the bacteria is called a Hfr bacteria (high
  frequency of recombination)
• It now initiates DNA replication and conjugation.

Since the F factor is incorporated in the
chromosome, It will transfer the entire
chromosome if possible. But the pilus is broken
most of the time before all Transfer can take
place.
49
R Plasmids and Antibiotic Resistance

• The genes conferring resistance are carried by
  plasmids, R plasmid (R for resistance).
• Some of these genes code for enzymes that
  specifically destroy certain antibiotics, like
  tetracycline or ampicillin.
• Plasmids can be passed along from bacteria to
  bacteria by conjugation or transformation.

50
Antibiotic Resistance