VIRUSES AND PRIONS (WEEK 3)

What can viruses infect?

• all living things but is very specific for the host they infect

• animal viruses that infect humans

• bacteriophages that attack bacteria

What is a virus?

• very small and can easily pass through bacterial filters

What are the characteristics of a virus?

• 10-900+ nm and is visible with an electron microscrope

• acellular, lacks cellular features like ribosomes, non living

• only nucleic acid surrounded by proteins

• lacks ability to replicate by itself

• highly obligate intracellular parasites

• no enzymes for energy production or protein synthesis

What is a virion?

• a fully developed infection viral particle which allows transmission between host cells

What do virions contain?

• nucleic acid

• capsid

• envelope

What are the nucleic acids in a virion?

• DNA or RNA but never both

• single stranded or double stranded

• linear or circular

• 1000 - 250k nucleotides

What is a capsid?

• protein coat surrounding the nucleic acid

• made of capsomeres

• can come helical, polyhedral, or complex

What is an envelope?

• phospholipid bilayer cover for capsids containing carbs and proteins

• derivative from the host cell membrane

• may have spikes

What are spikes?

• glycoproteins used to attach to host cells

• can be present on both enveloped and non enveloped viruses

What are the enveloped viruses?

• HIV

• Hepatitis B

• influenza

• coronavirus

What are the non enveloped viruses?

• adenoviruses

• norovirus

What is the viral taxonomy?

1. type and amount of nucleic acid

2. capsid shape

3. size at 10-300nm

4. envelope presence

5. type of host the virus infects

6. disease and symptoms based on cell type targeted

7. replication strategy

How do we name a virus?

• order, family (-viridae), genus (-virus), species (not latinized), variants

example (HIV):

• family: retroviridae

• genus: lentivirus

• species: human immunodeficiency virus

• sub species: HIV-1, HIV-2

How does viral replication work?

• virions only have nucleic acid present

• nucleic acids contain instructions to make the capsid + enzymes that process their nucleic acid

• everything else comes from the host

What is the animal virus lifecycle?

1. attachment

2. entry

3. uncoating

4. biosynthesis

5. assembly

6. release

What is the attachment step in animal virus replication?

• host cells contain receptor sites for viruses to attach

• receptor sites are inherited and can vary

• viruses have attachmant sites all over (ex. spikes on enveloped, fibers on non eveloped)

What is the entry step in animal virus replication?

• entire virion enters the host cell

• endocytosis in non enveloped viruses

• fusion in enveloped viruses

What is the uncoating step in animal virus replication

• virus genetic material is released from the capsid

• enzymes from cytoplasm or lysosome help break capsid

• endosome has reduced pH

What is the biosynthesis step in animal virus replication?

• cell metabolic pathways are hijacked

• new virions are formed

• procedure varies whether its DNA or RNA

What occurs in biosynthesis for DNA viruses?

1. viral DNA migrates to nucleus and its instructions are used to make viral proteins

   1. mRNA is transcribed and moves to cytoplasm

   2. mRAN translated by ribosomes to produce capsid proteins

2. copies of complete viral DNA are made in nucleus

What occurs in the assembly for DNA viruses?

• capsid proteins return to nucleus and combine with replicated viral DNA to form new virions

• examples: herpesviridae / cold sore and chickenpox, adenoviridae / common cold

What occurs in the biosynthesis of RNA viruses?

• RNA to protein but also RNA to RNA

• more complex and varies depending on RNA virus type

• viral RNA is directly used to produce viral proteins without DNA or nucleus involvement

What occurs in ssRNA biosynthesis?

• cell treats viral RNA as mRNA and translates it into viral proteins

• RNA viral genome is copied using viral enzyme RNA dependent RNA polymerase

What occurs in the assembly for RNA viruses?

• occurs in the cytoplasm of the cell

• examples: picornoviridae / polio, rhabdoviridae / rabies, sars-cov-2 / COVID -19

What occurs in the biosynthesis of retroviruses?

• RNA to DNA to RNA to PROTEIN

• example: HIV-1

  • virion contains viral genome ssRNA and enzymes reverse transcriptase, integrase, and protease

What is the life cycle of retroviruses?

1. ssRNA is reverse transcribed into dsDNA

2. dsDNA is integrated into host DNA to form provirus

   1. provirus is replicated when host cell replicates

   2. provirus can remain inactive or switch on to produce new viruses (inactive vs active infection)

3. assembly at plasma membrane and release

What occurs in the release step of animal virus replication?

• viruses escape from the host by cell lysis, exocytosis, or budding

What is lysis?

• for non enveloped viruses (e.g. norovirus)

1. cell membrane is ruptured

2. cell bursts and disperses virus

3. results in cell death

What is exocytosis?

• for non enveloped viruses

• vesicle around virus fuses with membrane; host cell does not die

What is budding?

• for enveloped viruses (e.g. HIV)

• a portion of the cell membrane becomes the virus envelope

• specific viral proteins may become attached to the membrane

How do viruses cause disease?

• viruses enter cells, use cell’s machinery to replicate, then leaves to infect other cells, causing disease

• cell is too busy making viral components

• viruses consume nutrients, leaving none for host

• viruses can make products that are toxic to the host

What is a normal cell?

• divides only under the right conditions

• process is tightly regulated by proteins

How can we identify a cancer cell?

• if a virus contains an oncogene

• if a virus integrates into host DNA and switches on oncogene activity

What are examples of oncogenic DNA viruses?

• human papillomavirus (HPV)

• hepatitis B

What are examples of oncogenic RNA viruses?

• t cell leukemia viruses

• hepatitis C

What is acute infection?

• symptoms appear quickly

• infection removed quickly

• example: colds

What is a latent infection?

• virus hibernates in host and does not produce disease until a later time

• example: HIV

What is a chronic infection?

• symptoms appear gradually over a long period (typically fatal)

• example: hepatitis

What are prions?

• proteinaceous infectious particle

• abnormal protein that causes disease

• misfolded form of a normal protein

What is the infectious nature of prions?

• prions on contact with the normal protein will convert it to the disease form in a chain reaction

• PrPsc accumulates in cell as it is resistant to degradation and causes cell death

What is transmissible spongiform encephalopathies?

• TSEs = fatal neurodegenerative diseases in both humans and animals

• causes motor and cognitive decline, and dementia

What are examples of TSEs?

• bovine spongiform encephalopathy (BSE or mad cow disease)

• scrapie in sheep

• creutzfeldt-jakob disease (CJD; humans)

How is TSE transmit