Ch 19 Viruses

Q: Are viruses alive?

 

“Borrowed life” between life forms and chemicals

Intro: TMV small enough to fit through filter

            Not cells

            Infectious particles

1.     nucleic acid (DNA, RNA, sl, dbl.)

a.     4 to 1000 genes vs. bacteria 200 to few thousand

2.     capsid (protein coat built from capsomeres)

            Accessory structures

- membranous envelope derived PO4 lipids from host    (many animal viruses)

- proteins and glycoproteins of viral origin

- some viral enzymes ex. Reverse transcriptase

            Host range of obligate intracellular parasites

 

PBS: evolve aids video/lecture

 

19.2 Viruses reproduce in host cells only

Obligate intracellular parasites

PARASITE- HOST EVOLUTIONARY FLUX

-       host range : evolution of recognition systems by viruses (lock n key fit)

§  receptors may have originally been beneficial for host

broad vs specific even tissue type

 

A.    General features of viral repro cycle

a.     Infection

                                                       i.     Phage injects

                                                     ii.     Endocytosis

                                                   iii.     Fusion of envelopes

B.     Reproductive cycles of phages

a.     Double stranded DNA

                                                       i.     Lytic (cell death) : Virulent phage is only lytic

                                                     ii.     Lysogenic: Does not destroy host cell

Ex. Lambda temperate phage

     

Temperate phage: Lytic and lysogenic cycles (lambda)

Lysogenic: prophage  (inserted viral DNA)

DNA inserts into a specific place in E.coli by viral proteins

A prophage gene prevents transcription of other prophage genes

- can cause host bacteria to secrete toxins

                   - diphtheria, botulism, scarlet fever

- environmental signals trigger prophage to pop out = intitiate lytic cycle

Q: What is an advantage of the lysogenic cycle?

 

Q: What are some mechanisms bacteria employ for protection?

 

Bacterial “protection”

  1. mutant w/o receptors
  2. methylated DNA and restriction enzymes
  3. lysogeny

 

Reproductive cycles of animal viruses

***key variable: viral genome is the basis for classification

*almost all animal viruses have an envelope and RNA

Viral envelopes

1.     used to enter the host

a.     viral glycoproteins (made by host RER) bind to the host receptor cell

b.     host ER and Golgi body add sugars

c.     exocytosis (plasmamembrane)

2.     some viral envelopes are derived from the nuclear envelope 1st then shed if in cytoplasm

a.     ex. Herpesvirus: dbl DNA repro in host nucleus

                                                       i.     replicate and transcribe DNA

                                                     ii.     copies of viral DNA remains behind (latent) can hide in some nerve cells

                                                   iii.     stressor= infection of other cells leading to blisters

 

Retroviruses: most complex RNA animal viruses

1.     reverse transcriptase (RNA to DNA)  ex. HIV

2.     enveloped as well

3.     2 identical single stranded RNA

 

Provirus: integrated viral DNA never leaves the host genome

Prophage: leaves the host genome when starts the lytic cycle

 

http://www.scienceinreview.com/2007/3d-animation-of-hiv-infection.html

            CD4 and CCR5 involved in HIV dual docking mechanism

                          CCR5 gene missing then immune to HIV

 

 

Evolution of Viruses

 

Q: when did viruses 1st evolve? Evidence?

 

Because viruses depend on cells for propagation = evolved after cells  (possibly multiple times)

** hypothesis: viruses originated from naked bits of cellular nucleic acid moving between cells (maybe injured cell surfaces)

 

Candidates for original sources of viral genomes

-       plasmids (bacteria, yeast)

-       transposons (DNA segments that can change location)

 

3 types of mobile genetic elements :

            1. virus

            2. transposons

            3. plasmids

Viral genes more in common with host cell genome

Some viral genomes are similar although seemingly distantly related

Some plant and animal viruses share similar sequences = evolved early in EUK?

 

Mimivirus (largest, dbl DNA) icosahedral capsid

            1.2 million bases ~ 1000 genes

            Some appear to code for products for cellular genomes

                        Ex. Translation, DNA repair, protein folding and polysachhardie synthesis

 

            DEABTE ON ORIGIN OF VIRUSES

 

19.3 Viruses, viroids, prions are formidable pathogens for plants and animals

A. Animal- viral diseases symptoms are produced via:

            Causing release of lytic enzymes from lysosomes

            Cause infected cells to produce toxins

            Some molecular components  are toxic themselves (envelope proteins)

 

Damage = infected tissue ability to regenerate ex. Et of throat versus mature nerve cells form polio

 

Vaccines:

No antibiotics since these target prokaryotic enzymes

There are a few viral enzymes though

Antiviral drugs resemble nucleosides = interfere with nucleic acid synthesis

            Ex. Acyclovir: impedes herpes by inhibiting viral polymerase for DNA

            Ex. Azidothymidine (AZT) messes with reverse transcriptase of HIV

 

Emerging Viruses:

HIV (1980s) 1959 Belgian Congo

Ebola (1976) Central Africa: causes hemorrhagic fever

Encephalitis

West Nile virus : N America 1999

Severe Acute Respiratory Syndrome (SARS) China 11/2002 in 8 months infected 8000 killed 700

H1N1

 

Remerging Diseases : tuberculosis, syphilis

 

3 processes contribute to emergence of viral diseases

1. mutation of existing viruses

            RNA viruses: unusually high mutation rate (no RNA proofreading)

            Ex. Flu: flu epidemics (new strains of influenza)

2. dissemination of a viral disease from a small human population

3. spread of existing viruses from other animals

            ~3/4 new human diseases originate

            Natural reservoir: animal harbors virus but is not harmed

            Bats – SARS

 

3 types of influenza:  polymerase has 3 subunits

B and C: infect only humans no epidemic

A: birds, pigs, horse, humans, = major flu epidemics: Spanish flu of 1918  (birds) 40 million died

 

If animal is infected with multiple strains of flu virus = can undergo genetic recombination and then can possibly infect humans

 

1918 H1N1 virus: 2 viral surface proteins

                        Hemagglutin – 16 types of protein helps flu virus attach to host cell

                        Neuraminidase – 9 types of enzyme helps release virus from cell

 

2009 H1N1 influenza adopted novel strategies to move from birds to humans = more virulent

            Adopted a new mutation in one of its genes distinct form the 1918 flu, 1957, 1968

Prior bird crossovers had a specific mutation in the birds polymerase gene  allowing the protein the work efficiently in humans as well

1.     H1N1 retains the bird version of polymerase but has a 2nd mutation that seems to suppress the ability of human cells to prevent the bird polymerase from working

2.     another strategy not used before and increases virulence even more , when a human subunit is substituted for one of three protein subunits that make up bird polymerase = new combination is efficient in human cells

this rare mutation and combination shows there may be more ways to become virulent

 

UC Berkeley: Doudna and Mehle trying to see if they can predict more accurately how it will evolve and help drug research

H stands for the hemagglutinin surface protein= Mutations allow virus to enter human cell

**mutations in thepolymerase gene are key to ability to replicate inside a human cell

            Human cells prevent 3 bird subunits for polymerase to assemble

-       a single switch at position 627 on 2nd subunit allows polymerase to overcome this inhibition

o   when glutamic acid normally founding birds is switched foe lysine( typical in humans )

o   the surface charge of the subunit changes from acidic (-) to basic (+) and allows the subunits to assemble

§  LYSINE in that position in mammals increases viral replication  and transmission and sometimes pathogenicity

            H1N1 has 2 rare mutations in the 2nd subunit:

            Serine at position 590                         and       Arginine at 591    most common in pigs, this combination has the same affect as the substitution at 627 allowing polymerase complex to form

 

 

 

B. Viral Diseases in Plants over 2000

Common signs – bleached or brown spots on leaves, fruit or stunted growth

Most plant viruses are RNA (helical or icosahedral capsid)

 

Viral diseases in plants spread in 2 ways

  1. horizontal transmission: infected from an external source via wind, injury, herbivore, insects
  2. vertical transmission: inherits viral infection from parent
    1. asexual propagation
    2. sexual: infected seeds

 

once virus is in the plant, spreads via plasmodesmata  )actually get enlarged by viral macromolecules)

 

Viroids and Prions: the simplest infectious agents

Viroids: circular RNA (few hundred nt’s) infect plants

            -do not encode proteins

            - can replicate in host cells

            -cause errors in regulatory systems controlling plant growth

 

Prions: infectious proteins

Cause degenerative brain diseases in animals

            Scrapie: sheep Mad Cow, Creutzfeldt Jakob  and Kuru in humans

                        2 characteristics:

                        1. act slowly ! incubation 10 years before symptomatic

                        2. virtually indestructible

                                    Not destroyed by heating to normal cooking temp

            Proteins cannot replicate themselves – hoe transmissible pathogen?

Prion: misfolded protein in brain gets inside a cell with a normal folding protein > prion converts normal folding into misfolded version

 

Prions aggregate together in a complex which interferes w/nirmal cell function