CH. 13 - Viruses and Prions

Virus

a non-living, infectious particle

• includes naked viruses and enveloped viruses

Naked Viruses

composed of a capsid which surrounds the nucleic acid

• capsids can also be a nucleocapsid

• Many have spike proteins projecting off their surface

  • Help virus attach to specific receptors on host cell

Capsid

Protein coat composed of subunits called capsomeres

• can be isometric (icosahedron), helical, or complex

Nucleocapsid

Capsid + nucleotide = nucleocapsid

Isometric (icosahedron) Capsid

looks like a geometric 3D shape

• very common

Helical Capsid

cylinder shaped

Complex Capsid

looks kinda like a robot with spider legs

Enveloped Viruses

A naked virus surrounded by a lipid bilayer

• Lipid bilayer is called an envelope

• Virus doesn’t make its bilayer, it steals a section of its host cell and wraps it around itself

• Matrix proteins line the interior of the lipid bilayer and have a function in releasing the virus from the host cell

• Many have spike proteins projecting off their surface

  • Help virus attach to specific receptors on host cell

Virus Structure and Size

• Viruses have nucleic acids

  • can be DNA or RNA, but never both

  • can be single or double stranded, but never both

  • viral DNA can be circular or linear

  • viral RNA can only be linear

• Viruses are 100 to 1,000x smaller than the cells they infect

  • 10nm – 500nm

Virus Replication

• Viruses dont have enough genetic info to self replicate, so they essentially force host cells to do it for them

  • this makes them obligate intracellular parasites

• Viruses are very specific to host cells they infect

  • Specificity is due to the attachment of the virus

  • Host cell has to have a receptor that the virus can bind to

  • means they are host/tissue specific

• Will use host cell machinery to assemble viral specific molecules instead of the normal macromolecules it makes

Obligate Intracellular Parasites

This means that outside of the host cell, they are just a particle

• Once they attach to a host cell and get their genetic info, they can force host cells to produce viral cells

Host Tropisms

Viruses that are specific to a host and cant infect other types of hosts

ex) A virus that infects cats but cant be passed to humans

Tissue Tropisms

Viruses that attach to receptors only found in a specific tissue type

Ex) flu virus only attaching to cells in respiratory tissue

Virus/Host Cell Interaction Flow Chart

1. a virus infects a host cell

2. either disease of the host cell or genetic alteration of host cell occurs

3. if disease of host cell occurs, we get a productive infection, and more virus is produced

4. when these viruses are released, 2 things can happen: either the host cells lyse, or the host cells don’t lyse

5. If the host cell lyses, it dies. If the host cell does not lyse, it multiplies, causing the continuous release of virions (chronic infection)

6. if genetic alteration of the host cell occurs, the host cell experiences a latent state

7. In this latent state, the viral DNA is integrated into the host cell genome, but no new viral particles are being produced

8. Then, the host cell will multiply, but the phenotype is changed because of the viral genes that are integrated in the chromosome, causing the cell to not work right

Productive Infection

an infection that results in the production of more viral particles

Chronic Infection

When host cell doesn’t die and continues to produce viruses

Bacteriophage Lytic Replication

Replication that ends in the lyse of the host cell

Achieved in 5 Steps:

• Attachment

• Genome Entry

• Synthesis

• Assembly

• Release

All viruses are essentially going to use these 5 steps

Attachment in Bacteriophage Lytic Replication

Bacteriophage attaches to specific receptors on the bacteria

• mediated by tail fibers

Genome Entry in Bacteriophage Lytic Replication

Injection of the the bacteriophage DNA into the bacterial cell

• bacteriophage is going to change shape and inject its nucleic acid into the bacterial cell

• They don’t enter the cell, they inject their nucleic acid into the cytoplasm of bacterial cell

• Now the genetic info can be expressed once in cytoplasm

Synthesis in Bacteriophage Lytic Replication

In this stage, bacterial machinery makes all the parts we need to make a new bacteriophage

Assembly in Bacteriophage Lytic Replication

In this stage, we start to put all the pieces together to assemble a mature/active bacteriophage

• Bacteriophage assembly doesn’t require proteins or enzymes, it happens automatically

Release in Bacteriophage Lytic Replication

Where we release the assembled bacteriophage by lysing the host cell (break it open to release the bacteriophage)

• bacteriophage has lysozyme to break through the cell wall and lyse the cell, releasing the bacteriophage

• Then it will float around and look for a new host cell to infect

Lysogeny

1. bacteriophage attaches to surface of bacterial cell and injects its nucleic acid

   1. Bacteriophage has to make a decision of lytic replication or lysogeny

   2. If it chooses lysogeny…

3. Genetic info is inserted into bacterial chromosome

   1. This creates a lysogen, which is a cell in a state of lysogeny (latent state)

   2. When the bacteriophage genetic info is integrated in the bacterial chromosome, it’s called a prophage

4. Once lysogeny is established, the bacterial cell will go about its normal business of growing and dividing

   1. Each time it divides it replicates chromosome, also replicating the bacteriophage DNA

   2. All the daughter cells will have it as well

5. Lysogeny can last indefinitely

6. If there is damage to the host cell, that bacterial cell will die and take the bacteriophage with it

7. So, if the bacterial cell looks like it might die, the bacteriophage will leave the bacteria and try to find a host cell where it can complete lytic replication

What type of bacteriophage uses lysogeny?

Only temperate bacteriophages use lysogeny

Lysogenic Conversion

the process where a lysogenic bacteriophage transfers genes that encode toxins to a bacteria

• This new genetic information is often carried on a prophage

• Bacteria carrying the prophage will produce the toxins/virulence factors, which cause disease

• There are a number of diseases caused by bacteria that have undergone lysogeny

  • Streptococcus pyogenes (scarlet fever)

  • Clostridium botulinum (botulism)

  • Corynebacterium diphtheriae (diphtheria)

Bacteriophage in Transduction (General and Specialized):

Transfer of bacterial genetic information using bacteriophage

• Generalized Transduction

  • Bacterial chromosome is chopped into little bits and a random piece is packages inside a bacteriophage to make that transducing particle

• Specialized Transduction

  • Only occurs during lysogenic infections

  • Prophage takes some of bacterial DNA when leaving the chromosome

  • Packaged into virions

  • The DNA that can be transferred during specialized transduction is only the DNA next to where the prophage is located

Bacteriophage Specialized Transduction

Variation of transduction that only occurs if donor cell is in a state of lysogeny

• A temperate bacteriophage injects its DNA into the host cell

• bacteriophage DNA is integrated into the host cell chromosome, creating a prophage

• When this bacteriophage DNA isnt cut out correctly, we then have a piece of DNA that is part bacteria and part virus

• When you make new bacteriophages, they will have the hybrid piece of DNA

  • This is the transducing particle

  • This replication creates defective viral particles

• Bacteriophage injects the hybrid molecule into a bacterial cell

• Bc it doesn’t have all the bacteriophage genes, no new viruses can be made

• The bacteriophage DNA is degraded, and the bacterial DNA is integrated into the cell

Features of Viruses used to Classify Animal Viruses

• Genome Structure

  • DNA or RNA

  • Single or double stranded

  • single molecule or segmented

• Virus Particle Structure

  • isometric (geometric 3D shape)

  • helical (cylinder shape)

  • pleomorphic (irregular non-geometric shape)

• Presence or Absence of an Envelope

Classification of Animal Viruses (Family, Genus, Species):

Family

• Family name ends in -viridae

• Based on genome, virus structure, envelope

Genus

• Genus name ends in -virus

• Enterovirus, Rhabdovirus, Coronavirus

Species

• Name usually derived from disease caused: poliovirus, ebola virus, influenza virus

5 Steps of Animal Virus Replication

• Attachment

• Penetration and Uncoating

• Synthesis

• Assembly

• Release

Attachment in Animal Virus Replication

Virus attaches to receptor on host cell

• Protein spikes on virus recognize and bind to specific glycoproteins on the host cell

• Once the virus is attached, we need to get viral DNA inside

Penetration and Uncoating in Animal Virus Replication

• If it’s an enveloped virus…

  • they can fuse with the cell membrane of host cell, or they can enter through endocytosis (cell membrane wraps around the virus and internalize it)

• If a naked virus….

  • only enters through endocytosis

• In both cases, the viral particle is inside the host cell and needs to release its nucleic acid

  • To do this, they degrade the viral particle to release the nucleic acid (called uncoating)

Synthesis in Animal Virus Replication

The nucleic acid has to be targeted to the right place in animal cell so that synthesis of the viral particles can occur

• DNA viruses go to the nucleus

• RNA viruses go to the cytoplasm

Assembly in Animal Virus Replication

When we put together all the pieces to form a viral particle

• For enveloped viruses, assembly. .

  • puts together a nucleocapsid

  • modifies a section of the host membrane with viral proteins

  • Lines the interior with matrix proteins which serve as a docking center to show the nucleocapsid where it should attach

Release in Animal Virus Replication

To release itself from the host cell, enveloped viruses…

• Go through budding where it pushes through this part of the membrane with the matrix proteins. Membrane wraps around nucleocapsid, and then we release the new enveloped virus

• Can also leave through exocytosis

  • gets its membrane from some internal membrane bound organelle, then leaves through exocytosis

• Some will lyse the host cell to exit

Naked viruses…

• Can only leave through exocytosis

• Some viruses will lyse the host cell and exit that way as well

Shedding

The process by which the virus leaves the host animal to be spread to a new animal

• Viruses can be shed through the respiratory tract, urinary tract, etc

• Usually leave the same way they entered

Transmission

The way that a virus enters into a new host

• ex) droplets, skin contact, bodily fluids, etc

Acute Infections

• are short in duration (days to months)

• The infected cells will die

• The virus is shed during the infection and possibly transferred to new individuals

• Usually, the infected host will recover and develop immunity (cant be infected by that exact virus again)

Stages of Acute Infections:

• Prodromal stage

  • Infected with virus, reproducing virus, capable of passing on the virus, but not experiencing symptoms, may feel a little off towards end

• Disease stage

  • Suffering noticeable symptoms

  • Immune system is responding

• Convalescent stage

  • Starting to fell better

  • Immune system is eliminating the virus

  • Still infectious

Persistent Infections

• Last for a long period of time

• a lot are caused by enveloped viruses

• May or may not cause a disease

• people with persistent infections are carriers of the virus

• 2 categories:

  • Latent Infections

  • Chronic Infections

Latent Infections

Animal virus infects host cell and causes a state of latency

• so the cell is infected, but during latent state no new viruses are being made

Stages of Latent Infections

• You become exposed, and the virus multiplies

• Period of active symptoms

• Then you recover and are non-infectious, but the virus is still in you

• Immune system eliminates viral particles, but latency has been established, so some cells still hold viral genetic info

• Reactivation of the virus can happen later and cause you to experience active symptoms again

Chronic Infections and the Stages of Infection:

Continuous production of the virus

• Symptoms can be short in duration, but cells are still infected and you still continue to produce and release viruses for a long time

How can viruses cause cancer?

They make changes to the cell and cell proteins so that it undergoes unregulated cell division, leading to tumors

Tumor (neoplasm) and its cause:

Swelling/lump caused by abnormal cell growth

• Cause:

  • The non-functioning or malfunctioning of a protein that serves an essential role in cell growth/division

Benign Tumor Vs. Malignant Tumor

Benign tumor: tumor remains confined to a defined region

Malignant tumor: tumor spreads (metastasizes) to other parts of body

Proto-oncogenes

Genes that encode for proteins that function in the regulation of cell growth or differentiation

• If mutated, it is called an oncogene, which will then encode mutated forms of this protein, resulting in cancer

Viral Transformation

aka the conversion of a normal cell into a cancer cell

• Viruses inject DNA that carry oncogenes

• This leads to the expression of oncogenes

• Causes dysregulation in cell division, creating a cancer cell

• Transformation increases probability of cancer, it doesn’t always cause cancer

How do viruses transform cells?

Through the actions of retroviruses

Retroviruses

RNA viruses that become proviruses when they infect cells

• When they infect a cell, they convert their RNA into DNA using enzyme reverse transcriptase

• The DNA is then inserted into the chromosome of the host cell

• Once inserted into chromosome, its called a provirus

• Retrovirus carries oncogenes which can be expressed and cause cancer (unregulated cell growth) in that cell

What is viral host range and how is it determined?

Host range is the range of hosts a virus can infect

• Determined by the attachment step / the host cell receptors

  • Virus can only infect host cells if the host has the right receptor that it can recognize and bind to

• Some viruses can infect multiple hosts

• Cells can be infected with more than one virus type at a time

  • This makes it possible for the two viruses to swap bits of genetic info

  • Can result in a virus being able to infect a new type of host

  • ex) Pigs can be infected by bird flu and human flu

    • If they are infected with both, genetic exchange can happen between the viruses, so now the bird virus is capable of infecting humans (

    • called an antigenic shift

Prions

Proteinaceous infectious particles

• basically just infectious proteins

• If exposed to a prion, the prion can convert your normal proteins into prion proteins, causing a progressive neurodegenerative disease that is 100% fatal

• Cause Transmissible Spongiform Encephalopathies (TSE’s)

  • ex) mad cow, Kuru, Scrapie, Creutzfeldt-Jacob disease

• Are highly resistant to heat, chemicals, and radiation, making them almost indestructible

• Mainly acquired through consumption / handling of contaminated items

  • some forms can be genetic

• No treatment known

Replication of Prions

If you consume a prion protein, it will go to the CNS and interact with the normal protein and convert it into a prion protein

• they keep doing that until you have a lot of prion proteins in the CNS, causing neuro-degeneration

• In order for replication to happen, the normal protein (PrP ^C) must be present

  • The mutated form of the protein is called PrP^SC

• Types of prions usually stay within specific species

  • sometimes they can be spread between species, like Mad Cow disease

• It takes a long time after the initial exposure to exhibit symptoms (takes months to years)