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BI 234 > Lecture Four: Viruses & Prions > Flashcards

Lecture Four: Viruses & Prions Flashcards

1
Q

Amino Acid

A

Molecules that combine to form proteins

There are 20 amino acids, each with different chemical properties.

Which amino acids are in a protein, and what order they are in determines everything about what that protein will do in a cell.

The mRNA and coding strand both encodes an amino acid sequence used to make a protein

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2
Q

Coding Strand [DNA Transcription]

A

The coding strand (or informational strand) is the DNA strand whose base sequence is identical to the base sequence of the RNA transcript produced (although with thymine replaced by uracil).

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3
Q

Animal Virus

A

A small infectious agent that is unable to replicate outside a living animal cell.

Animal viruses contain only one kind of nucleic acid, either DNA or RNA.

Replicate differently than a bacteriophage ( with an animal virus, entire capsid enters via endocytosis or membrane fusion)

Replication Steps:

  1. Attachment/Absorption
  2. Penetration
  3. Uncoating
  4. Biosynthesis
  5. Maturation/Assembly
  6. Release
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4
Q

Bacteriophage

A

A virus that infects and replicates within bacteria and archaea

Replication steps:

  1. Attachment/ absorption
  2. Penetration
  3. Biosynthesis
  4. Maturation/assembly
  5. Release
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5
Q

DNA Polymerase

A

A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA.

“ase” = enzyme
“polymer” = what the enzyme makes, a polymer of nucleic acids
“DNA” = the specific polymer made by this enzyme

The virion contains an RNA-dependent DNA polymerase (reverse transcriptase)

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6
Q

Endoplasmic reticulum

A

A network of membranous tubules within the cytoplasm of a eukaryotic cell, continuous with the nuclear membrane. It usually has ribosomes attached and is involved in protein and lipid synthesis

Subunits of this are rough endoplasmic reticulum, and smooth endoplasmic reticulum

ERGIC: Endoplasmic reticulum / Golgi intermediate compartment

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7
Q

Enveloped virus

A

Virions that have an envelope which surrounds/covers the capsid:

Viral envelopes are phospholipid bilayers stolen from the host cell, either the nuclear envelope or the cell membrane

Embedded glycoproteins (spikes) are encoded in the viral genome (not stolen from the host)

Other envelope proteins & glycolipids, etc, are stolen from the host cell membrane

Envelopes in animal viruses have several purposes related to replication and transmission

Budding occurs in enveloped viruses

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8
Q

Genome Types

A

A characteristic of a virus and a component of virions

These determine the steps a virus must take to replicate in host cells

RNA or DNA

One or two strands
dsDNA
ssDNA
dsRNA
ssRNA
+ sense ssRNA
- sense ssRNA

Retroviruses are weird RNA viruses

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9
Q

dsDNA

A

Double stranded Deoxyribonucleic acid

They are antiparallel: the 5’ end on one is the 3’ end on the other. They are also complementary: every nucleotide on one strand base pairs correctly with a corresponding nucleotide on the other strand.

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10
Q

dsRNA

[only need to know what the abbreviation means]

A

Double-stranded Ribonucleic Acid

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11
Q

ssDNA

[only need to know what the abbreviation means]

A

Single-stranded Deoxyribonucleic acid

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12
Q

ssRNA

A

single-strand RNA

Two types: + sense ssRNA
- sense ssRNA

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13
Q

+ sense ssRNA

A

This is like mRNA and is directly translated by host ribosome; transcription is not needed

SARS-CoV-2 is an example of enveloped + sense ssRNA; causes COVID-19

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14
Q
  • sense ssRNA
A

This strand is complementary to mRNA; mRNA must be made based on this template.

Influenza is a enveloped, helical - sense ssRNA

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15
Q

Golgi Apparatus

A

A stack of small flat sacs formed by membranes inside the cell’s cytoplasm

Prepares proteins and lipid (fat) molecules for use in other places inside and outside the cell

During viral maturation, ER proteins get sent to the membrane via the Golgi

ERGIC: Endoplasmic reticulum / Golgi intermediate compartment

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16
Q

Host

A

The organism the virion attacks; can be bacteria or a human cell

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17
Q

Host Range

A

A Characteristic of Virus

The spectrum of hosts the virus can infect

Bacteria (viruses that infect bacteria are called
bacteriophage)
Archaea
Fungi & protists
Plants
Animals

Some viruses can infect a broad spectrum of hosts
Rabies: all mammals

Some only able to infect specific species
Bacteriophage lambda: only some strains of E. coli

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18
Q

Hemagglutinin (HA)

A

An Influenza-specific structure

H spike

A spike protein serving as a receptor for cell surface sialic acids, aids in attachment

Vital in the Attachment phase of viral replication

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19
Q

Matrix proteins

A

An Influenza-specific structure

In Biosynthesis: mRNA is translated into proteins
In the cytoplasm: proteins that will become nucleocapsid, matrix, RNA dependent RNA polymerases, and others, mostly for new virions.
In the ER: proteins that will be embedded in the membrane: spike proteins HA and NA, and a matrix protein

In Maturation/Assembly: New nucleocapsids are attached to a matrix protein that will help make sure the new virion has each of the 8 segments

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20
Q

Neuraminidase (NA)

A

An Influenza-specific structure

N spike

A spike protein that degrades protective mucin; aid in attachment

facilitates release from sialic acids during viral release; aids in release

In attachment: digests mucus

In entry and uncoating: Causes the virus envelope to fuse with endosome membrane . . . nucleocapsids are free!

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21
Q

Latency

A

Many viruses have different ways of “hiding” in host cells.

Incorporating the viral genome into the host genome is common
Retroviruses do this in humans, many bacteriophage do this
too

Other forms of latency exist
One example (from herpes viruses) is preventing the host
neuron apoptosis. If the neuron lives forever, so can the
virus particles!

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22
Q

Naked Virus

A

Non-enveloped virus

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23
Q

Nucleic Acid

A

Complex organic substance present in living cells, especially DNA or RNA, whose molecules consist of many nucleotides linked in a long chain.

Virus is a nucleic acid sequence

Found in and protected by virions

In uncoating: Nucleic acids are released into the cytoplasm

In biosynthesis: Direct the synthesis or proteins for capsid, enzymes, and spikes

24
Q

DNA replication (Polymerization Process)

[What enzyme does this; the template; the type of monomer; the product]

A

Definition: DNA replication is the process by which a molecule of DNA is duplicated; happens via base pairing, and constructing the opposite strand from 5’ to 3’

Enzymes: helicase, primase, DNA polymerase, and ligase

Template: each strand in the DNA double helix acts as a template for the synthesis of a new, complementary strand

Monomer: ??

Product: two DNA molecules consisting of one new and one old chain of nucleotides.

25
Q

Transcription (Polymerization Process)

[What enzyme does this; the template; the type of monomer; the product]

A

Definition: The process of making mRNA from DNA; occurs in the nucleus

Enzymes: RNA Polymerase

Template: DNA

Monomer: ??

Product: Single-stranded RNA molecule

26
Q

Translation (Polymerization Process)

[What enzyme does this; the template; the type of monomer; the product]

A

Definition: The process of making a protein

Enzymes: RNA-dependent RNA polymerase

Template: RNA

Monomer: ??

Product: Protein

27
Q

Prion

A

Misfolded proteins that can cause properly folded versions to also misfold.

Cause TSE: Transmissible Spongiform Encephalopathy

6 - 10 year incubation period

Symptoms:

  • Slow loss of alertness
  • Loss of coordination
  • Loss of weight
  • Delirium and death
  • “Spongy” regions of abnormal brain tissue
28
Q

PrPC

A

prion protein (cellular version) and found in all neurons

We don’t really know what PrPC does. We assume it stops working if it misfolds as PrPSC

29
Q

PrPSC

A

prion protein (scrapie version)

Infectious, misfolded, nonfunctional protein found in infected neurons

the neurons that contain PrPSC proteins die

deadly, and is very resistant to heat and radiation (worse than endospores)

30
Q

Bovine Spongiform Encephalopathy (BSE)

A

Prion disease infecting cow

aka Mad Cow Disease

Caused by someone feeding leftover butchered sheep to cows

Affected animals may display: changes in temperament (nervousness or aggression), abnormal posture, incoordination and difficulty in rising, decreased milk production, or loss of condition without noticeable loss of appetite

31
Q

Chronic Wasting Disease

A

Prion disease infecting deer and elk

Similar to other animal TSE, but very communicable but method of spread is unknown

Symptoms include The deer behave strangely, not hiding from humans / predators, and they eventually die within 2 years

So far no human infections

Deer shed huge amounts of PrPSC into the environment

Outbreak is quickly spreading in North America, with Idaho and Manitoba being the newest sites

32
Q

Creutzfeldt-Jakob disease

A

Prion disease infecting humans

Can be spontaneous with median age of victim 68 years old

Exposure to contaminated surgical instruments or infected organ

In both cases genetic risk factors are known

Symptoms include muscle twitching, progressive dementia

Death between 1 and 5 years with roughly 500 cases in the US every year

33
Q

Variant Creutzfeldt-Jakob disease (vCJD)

A

Prion Disease infecting humans

Most likely occurred when people hate BSE infected cows; also genetic risks

Symptoms occur years later; main symptoms are rapidly progressive dementia, muscle twitching, and psychological changes

Death is between months and years; faster than CJD

Median age of victim is 28

34
Q

Fatal Familial Insomnia

A

Prion Disease

Very rare, inherited prion disease in which neurons of the thalamus experience PrPSC conversion at a high rate.

Sleep is disrupted and can become impossible

Symptoms include cognitive declines, autonomic dysfunctions

Invariably fatal in ~1 year once symptoms appear.

Occurs to older people: 40-60 yrs old

35
Q

Kuru

A

Prion disease infecting cannibal humans

Common among the Fore people of Papua New Guinea; translates to “to shiver”

Spread by eating human brains

Symptoms include muscle twitching and loss of coordination, difficulty walking, involuntary movements, behavioral and mood changes, dementia, and difficulty eating

Once ritual consumption of human brains became rare, Kuru disappeared.

36
Q

Scrapie

A

Prion disease infecting sheep

Stanley Prusiner and his colleagues found abnormal proteins in spongiform tissue of sheep

Symptoms include subtle changes in behavior or temperament, intense frequent rubbing against fixed objects to relieve itching, gait abnormalities such as incoordination, stumbling

37
Q

Protein

A

A chain of amino acids

38
Q

Ribosome

A

A particle consisting of RNA and associated proteins found in large numbers in the cytoplasm of living cells.

They bind messenger RNA and transfer RNA to synthesize polypeptides and proteins.; the key to translation

Virions do not have ribosomes

Translates + sense ssRNA like it does mRNA

39
Q

RNA Polymerase

A

Use in the transcription of DNA to RNA

40
Q

RNA dependent RNA polymerase

A

An enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template.

One of the vProteins must be an RNA-dependent RNA polymerase since the host cell does not naturally have it

Necessary for - vRNA ⇢ + vRNA

  • ssRNA viruses must have an RNA dependent RNA polymerase in the virion
41
Q

Attachment / Absorption

A

First step of viral replication in both animal cells and bacteriophages

In Bacteriophages:

Critical step. Most of the host defenses attempt to prevent this

Requires a specific molecule to which the bacteriophage can attach (such as teichoic acid)

In Animal Cells:

Virus attaches to specific proteins and/or glycoproteins on host cell plasma membrane

Spike proteins typically help viruses attach to host cells (HA and NA).

Critical step hosts attempt to prevent. If attachment succeeds, the virus will probably kill or take over the cell.

In our cells, the main defenses after this point involve shutting down the cell or killing it!

42
Q

Penetration

A

Second step of viral replication in both animal cells and bacteriophages

In Bacteriophages:

Bacterial wall is breached by phage enzymes

Viral DNA or RNA is injected into cell

In Animal Cells:

virus enters via either: Receptor mediated endocytosis or
Membrane fusion

43
Q

Uncoating

A

Third step of viral replication in animal cells

Capsid and envelope (if present) are broken down to release nucleic acid into cytoplasm

Host cell ingests virion in through endocytosis

The endosome begins to acidify

M2 proton channel allows the inside of the virion to acidify
. . . this helps separate the nucleocapsids from the matrix

Neuraminidase causes the virus envelope to fuse with endosome membrane . . . nucleocapsids are free!

44
Q

Biosynthesis

A

The third step of viral replication in bacteriophages; the fourth step of viral replication in animal cells

This is the step where we see that viruses are nothing like cells.

This is also the step where their genome type dictates what they must force the cell to do.

The virus tries to make new virion parts, using host enzymes if possible.

All virions contain the viral genome, which for some viruses is DNA, and for others, is RNA.

In Bacteriophages:

The cell begins to translate viral RNA (if a RNA virus) or transcribe viral DNA (if a DNA virus)

The first proteins made regulate the host cell and alter transcription & translation.

Virus takes over the protein production: the cell starts to make capsomeres and spike proteins.

Host proteins are not made normally during this time.

Some viruses induce degradation of host DNA
Some viral proteins interfere with host gene transcription
Some viral proteins repress host gene translation

In Animal Cells:

Proteins for capsid, enzymes, and spikes must be synthesized, as directed by the viral nucleic acid.

Genome must be copied so that new virions can be made

Biosynthesis is the step where genome type matters (DNA/RNA)

45
Q

Maturation / Assembly

A

Fourth step of viral replication in bacteriophages and fifth step of viral replication in animal cells

In Bacteriophages:

Assembly of capsomeres into capsids around DNA core

In Animal Cells:

Capsid is assembled around the genome & any internal enzymes (if there are any)

If enveloped, spike proteins are inserted into host cell membrane or nuclear membrane into the part of the membrane that will become the envelope!

Envelope wraps around capsid

46
Q

Release (lysis)

A

Fifth step of viral replication in bacteriophages and sixth step of viral replication in animal cells

In Bacteriophages:

Other viral proteins cause host cell lysis

Host cell bursts, releasing the virions and killing the host cell

about 50 - 200 new phages produced

In Animal Cells:

Release: one of these:
Lysis
Occurs with non-enveloped viruses
Host cell bursts releasing viruses, can result in tissue death

Budding
Occurs with enveloped viruses
Exocytosis-like exit from the host cell; host cell remains viable (but is a virion-producing zombie

47
Q

Tissue Tropism

A

A Characteristic of Virus

Aka Viral Tropism

Tissue tropism is the spectrum of cells/tissues the virus can infect

Mostly for animal viruses

Often not known, but the key is that viruses tend to specialize in using certain pathways to enter host cells

For example, SARS-CoV-2 virions must attach to the enzyme ACE-2 and/or receptor TMPRSS2 as part of cell entry

The cells that display ACE-2 help explain the various forms of COVID-19

Many influenza viruses must attach to specific sialic acids

Typically you hear this as in “SARS-CoV-2 has a tropism for respiratory epithelia”

48
Q

Transmissible spongiform encephalopathy

A

Diseases caused by prions

aka Prion Diseases

49
Q

Virion

A

the complete, infective form of a virus that moves between host cells, with a core of RNA or DNA and a capsid.

“Virus Particles”

Their only job is to enter a new host cell and safely deliver the nucleic acids; this is the only thing they can do.

They encode proteins that will be synthesized by the host cell:

Structural proteins that will become part of new virions

In some cases, nucleic acid synthesizing proteins (RNA polymerases, DNA polymerases, reverse transcriptase)

These are often necessary for making nucleic acid copies for new virions

Enzymes that steal host components (such as 5’ caps) for use in viral replication

Regulatory proteins that change the cell’s behavior

Virions are non-motile, don’t communicate with other virions, do not secrete toxins or anything else, are immune to antibiotics and antivirals (antiviral medications attack other stages of the virus cycle).

50
Q

Capsid

[what molecule(s) make up the structure]

A

A virion structure

Protective protein shell around the core

Often repeating geometric shapes

Sometimes an envelope encases the capsid

51
Q

Capsomere

[what molecule(s) make up the structure]

A

A virion structure

Proteins which make up the capsid

Capsid shapes reflect the shapes of capsomeres

52
Q

Envelope

[what molecule(s) make up the structure]

A

A virion structure

Only present in some viruses

phospholipid bilayers stolen from the host cell, either the nuclear envelope or the cell membrane

Embedded glycoproteins (spikes) are encoded in the viral genome (not stolen from the host)

Other envelope proteins & glycolipids, etc, are stolen from the host cell membrane

Envelopes in animal viruses have several purposes related to replication and transmission.

Envelopes of bacteriophage have unknown functions and sources

Envelopes trick our immune systems

Host cell membrane identifies itself with glycoproteins; the virion steals this!

Envelopes allow easy fusion with new host cell membrane: this provides a route of entry

Envelope help the virion avoid drying out (this keeps them active in the air, for example)

Envelopes affect our disinfection choices

Solvents such as alcohol do not affect naked viruses!

Anything that can disrupt a lipid membrane can inactivate enveloped virions!

Only budding, and NOT lysis, occurs with enveloped viruses

53
Q

Genome

[what molecule(s) make up the structure]

A

A virion structure

RNA or DNA genome found in the capsid

54
Q

Spike Proteins

[what molecule(s) make up the structure]

A

A Virion structure

Can have several functions, but most have one that attaches to the outside of the host cell.

Hemagglutinin (HA) and Neuraminidase (NA) are spike proteins

55
Q

Virus

A

The nucleic acid sequence that encodes information to reprogram a host cell to make “virus particles” or “virions.”

A virus is information.

Effects of viruses:

Cell damage (cytopathy) and cell death

Immune responses such as interferon production (in animals) or CRISPR/CAS activation (in bacteria)

Mutations (if the virus alters the host genome)

do not all share a common or universal ancestor

They do not have a place in this universal phylogeny

BI 234 (4 decks)

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