Virus Lecture Sep 9 Flashcards

1
Q

In what three ways are human viral pathogens classified?

A
  1. virion structure
  2. genome organization
  3. replication strategy
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2
Q

WHat is the infectious virus particle called?

A

virion

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3
Q

How do viruses produce disease? How do they NOT produce disease?

A

They produce disease by multiplying. THey do not cause disease by producing toxins.

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4
Q

Viral genomes are —loid, except for retroviruses which are —loid.

A

Viral genomes are haploid except for retroviruses whch are diploid.

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5
Q

What are the different possible genomic orgnizations?

A

dsDNA

ssDNA (+ or -)

dsRNA

ssRNA (+ or -)

they can be linear or circular (some linear RNA genomes are segmented)

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6
Q

Where are the capsomeres encoded?

A

In the viral genome

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7
Q

In general, what are the two potential capsid shapes?

A

helical (cylindrical) or icosahedral (cubic)

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8
Q

What are viral attachment proteins?

WHere are they located in naked viruses? In eveloped viruses?

A

The VAPs are proteins that interact with receptor on the target cell to facilitate penetration.

In naked viruses the VAPs are located on the capsid itself.

In enveloped viruses the VAPs are located on the envelope.

They just need to be on the outside of the cell.

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9
Q

What two roles do VAPs play in enveloped proteins?

A

VAPs help the virus adhere and penetrate cells.

Then when new viral particles are being assembled, VAPs are placed in the host cells cytoplasmic membrane and signal whhere the virions should bud out.

As they bud out they take the membrane with the VAPs with it to form the envelope

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10
Q
A
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11
Q
A
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12
Q

What’s special about retroviridae viruses?

A

They are the only ones that are diploid.

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13
Q

What’s special about orthomyxoviridae viruses?

A

They have segmented linear genomes

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14
Q

Will helical-capsid viruses always have an envelope or never have an envelope?

A

They always have an envelope

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15
Q

What three things does viral host range depend on?

A
  1. Can the virus enter the cell?
  2. Can the virus find/use the appropriate cellular machinery?
  3. Can the virus exit the cell?
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16
Q

What is the difference between a productive infection and a non-productive infection?

A

Viral infections of cels that yield new infectious viruses are called productive (lytic)

Non-productive viral infections occur when the viral genetic material persists in a cell (latent state) but no infectious virus is formed

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17
Q

What are the 6 phases of viral multiplication?

A
  1. attachment
  2. penetration
  3. uncoating
  4. virus component synthesis
  5. assembly
  6. release
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18
Q

What are cytopathic effects?

A

Cytopathic effects are morphological changes to the host cell that result from the synthesis of viral proteins and viral effects on host macromolecular synthesis

Examples are cell rounding, cell fusion, etc.

Some herpes viruses have the ability to synthesize a protein in their envelope which allows the enveop to fuse with the host cell. Because the protein stays in the host cell membrane, infected cells will adhere to uninfected cells forming multinucleated giant cells

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19
Q

How does a naked virus release it’s nucleic acid into the cytoplasm of the cell?

How do enveloped viruses release their nucleic acid into the cytoplasm? THere are two ways.

A

When the virus penetrates the cell it’s placed into a lysosome, where the capsid is degraded, releasing the nucleic acid.

An enveloped virus can do one of two things. It’s membrane to can fuse with the cytoplasmic membrane, dumping the nucleic acid out into the cytoplasms.

Or…It the virus can penetrate without losing its envelope, in which case it’s brought into a lysosome. The viral envelope then fuses with the lysosomal membrane and the nucleocapsid is ejected.

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20
Q

Where do DNA viruses replicate?

Where do RNA viruses replicate?

What are the two big exceptions to this rule?

A

All DNA viruses replicate in the nucleus because it needs the DNA polymerase enzymes that are only located in the nucleus.

THe vast majority of RNA viruses replicate in the cytoplasm.

The two big exceptions are AIDs and Influenza virus, both of which replicate in the nucleus.

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21
Q

What is a viroporin?

A

A small hydrophobic virus-encoded protein that oligomerize at host cell membrane where they are involved in enveloped virus budding and non-enveloped virus cellular lysis

THey have several cytopathogenic effects on the cell including the formation of hydrophilic pores and alterations of calcium and hydrogen gradients

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22
Q

How do naked proteins get out of a cell?

How do enveloped viruses get out of a cell?

A

Naked viruses lyse the cell

Enveloped viruses bud out

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23
Q

If enveloped viruses can leave host cells through budding, how does the host cell die because of the infection?

A

BUdding does not lyse the cell.

The cell is attacked by the immune response because budding requires that the VAPs be placed on the host cell’s cytosolic membrane.

The immune response then recognizes the cell as forieng and mounts a response against it.

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24
Q

Describe a one step growth cycle for a virus.

What is the eclipse period?

What is the latent period?

A

FIrst there is an initial dip when the virions per cell reaches almost 0 – this occurs because all the first viruses get absorbed into the cell.

After a while, you get infectious virus formed. Up to the time point when virions begen to form WITHIN the cells is the eclipse period.

As time passes, these intracellular virions mature and leave the cell. The time up to this point is the latent period.

When the curve reaches its peak, that is the yield or burst size. The total number of virions produced.

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25
Q

Will a cell that is actively replicating host a virus with a shorter or longer eclipse period?

A

Shorter. The cell is already replicating and the virus will therefore multiple much faster.

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26
Q

Describe the one step growth cycle for mRNA, DNA, early protein, and late protein within a host cell.

A
  1. THe first to form is the mRNA
  2. Soon after the mRNA beings to icnrease, a series of early viral proteins are translated. These early proteins are involved in the replication of nucleic acid
  3. About 6 hours after adsorption, DNA begins to increase
  4. Shorterly after this, early protein synthesis subsides and late proteins are synthesized. Late proteins are the structural proteins of the virus such as the envelope proteins or the nucleocapsid proteins.
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27
Q

Are all negative sense RNA viruses enveloped or naked?

A

enveloped

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28
Q

Why must RNA viruses produce their own replicase/transcriptase?

A

Because they replicate in the cytoplasm and the host cell doesn’t have cytopasmic RNA polymerase

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29
Q

What two families of RNA viruses do NOT replciate in the cytoplasm?

A

Orthomyxoviruses (i.e. influenza)

and retroviruses (HIV)

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30
Q

All ss RNA viruses (except retroviruses) repliecate via a ———- ——— intermediate.

A

All ssRNA viruses except retroviruses replicate via a ds RNA intermediate

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31
Q

Why are RNA viruses more likely to undergo spontaneous mutation than DNA viruses?

A

Because viral RNA polymerase is not as accurate in duplication as the host cell’s DNA polymerase is.

32
Q

Reproviruses are initially replicated in the nucleus or cytoplasm?

A

They all have an initial nuclear phase, involving a reverse transcriptase in their genomic RNA replication.

33
Q

What are two ways RNA viruses have developed to produce individual polypeptides from polycistronic RNA (since this is not a property of eukaryotic cells)?

A
  1. Some (like picornavirus) synthesize polypeptides that are then cleaved by viral proteases
  2. Others have individual intiation and termination signals that appear throuhgout the RNA strand (Rabies does this)
  3. The segmented RNA genomes (orthomyxoviruses) usually have only one or two genes per segment.
  4. Polymerase will slide over various size intervening sequences to yield transcript of various compositions and lengths
  5. Retroviruses have spliced transcripts

Some viruses use a combination of these strategies

34
Q

With one exception, where does viral DNA replication occur?

What’s the exception?

A

In the nucleus.

The exception is poxviruses, which are big enough to carry their own enzymes to replicate entirely in the cytoplasm

35
Q

What phase must a host cell be in for DNA viral replication to occur?

A

The host cell must be in S phase because DNA viral replication requires the host replication machinery.

36
Q

All the DNA viruses except for —— can transform cells.

A

parvovirus

37
Q

If a host cell isn’t in S phase, what type of infection does a DNA virus cause?

A

A nonproductive or latent infection.

38
Q

What are three examples of dsDNA virus families?

A

Adenoviruses, herpesviruses, and papovariuses

39
Q

Describe the genome organization of replication strategy of hepadnaviruses.

WHat is the classic example of a hepadnavirus?

Why do HIV medications work on hepadnaviruses?

A

Their genome is interesting because it is partially double stranded DNA.

They replicate their DNA in the nucleus via a RNA intermediate.

This involves an RNA-dependent DNA polymerase–reverse transcriptase

They can transform cells–linked to liver carcinoma

  1. The partial dsDNA goes into the nucleus
  2. Covalently closed circular DNA is made
  3. From the dsDNA, pre-genome RNA is synthesized–this is a full legnth RNA copy of the DNA
  4. THe RNA leaves the nucleus and enters the cytoplasm
  5. In the cytoplasm more copies of the RNA are made plus individual messages (for the nucleocapsid proteins)
  6. As the RNA move sto the surface, it is acted on by reverse transcriptase to make dsDNA.
  7. The RNA is degraded as it is read
  8. THe core particle with viral DNA escapes the cell

Hepatitis B is the classic example.

HIV retrovirals that target reverse transcriptase will often be given for this as well.

40
Q

Explain the genome orgnization and replication strategy of parvovirus?

A

ssDNA genome

  1. enters nucleus trhough nuclear pores
  2. ssDNA forms hairpin tructures which self primes cellular polymerase to synthesize complimentary strand
  3. dsDNA uses cellular DNA polymerase and viral specific endonucleases to form genome DNA
  4. some strains need a helper virus (like an adeno-associated virus) to replicate
41
Q

Describe the genomic orgnization and replication strategy of poxviruses.

A

dsDNA without 3’ or 5’ ends

They are unusual because they replicate in the cytoplasm

They provide their own mRNA and DNA synthetic machinery

They code for viral DNA dependent RNA polymerase and mRNA modifying enzymes for processes like cappings and methylation

They also synthesize their own envelope

(they pack heavy)

42
Q

In general, how do viral infections lead to cancer?

A

Some RNA and DNA viruses cause a stable, inheritable change result in poor or no control of cellular division (cellular transformation) in certain infected cells

43
Q

What cells do DNA tumor viruses lyse and what cells do they transform?

A

DNA tumor viruses lyse permissive cells; they only transform non-permissive cells

So if the replication machinery doesn’t work, the cell will be transformed.

If the replication machinery works, the cell will be lysed.

44
Q

What cells do RNA tumor viruses transform?

A

Unlike DNA tumor cells, RNA tumor viruses will transform both permissive and nonpermissive cells

45
Q

Some RNA tumor viruses carry specific genes responsible for the transformation of host cells. What genes?

A

oncogenes

46
Q

What can cellular transformation result in?

A

Cellular transformation results in the alteration of cellular processes and properties which can result in altered morphology, growth control and cellular and biochemical properties

47
Q

How do all tumor viruses orgnize their genomes?

A

All tumor viruses are DNA viruses

OR generate a DNA provirus (like retroviruses)

48
Q

What 4 virus families are associated with human cancers?

A

papovaviridae

herpesviridae

hepadnaviridae

Retroviridae

49
Q

What virus in the papovaviridae family is implicated in human cancer? what cancer?

A

Human papillomaviruses are associated with genital tumors and squamous cell carcinoma

50
Q

What two viruses from the herpesviridae family are associated with human cancer?

What cancers?

A

EBV virus is associated with nasopharyngeal carcinoma, African Burkitt’s lympha, B-cell lymphoma

Herpes simplex type 2 is associated with cervical carinoma (?)

51
Q

What virus in the hepadnaviridae family is associated with human cancer? What cancer?

A

Hepetitis B virus is associated with hepatocellular carcinoma

52
Q

What virus in the retroviridae family is associated with human cancer? WHat cancer?

A

HTL virus is associated with adult T cell leukemia.

53
Q

What two proteins in the cell cycle act in tandem to shut off proliferation (act as tumor suppressants)

A

p110RB is the master brake in the cell cycle. If you have a functional p110RB protein you do not have uncontrolled growth because it shuts the cell division process off.

p53, when active, will turn on p21, which regulates cycline kinases which phosphorylate the p110RB to activate it and shut down cell division.

54
Q

What are cellular oncogenes?

What are proto-oncogenes?

A

They are mutated forms of normal cellular genes (mutations of proto-oncogenes)

Protooncogenes code for a heterogeneous group of proteins that are involved in normal cell division or differentiation pathways

Abnormal expression or regulation leads to cellular transformation or cancerous growth

55
Q

What are viral oncogenes?

A

V-onc are copies of cellular oncogenes which have been acquired by certain viruses during replication

so…they’re present in the viral genome

They’re responsible for the cellular transforming activity of those viruses which contain them–so infected cells will get the oncogene added to their genome and will become cancerous

56
Q

What are tumor suppressor genes?

What are the two main examples?

A

They are negative regulators of cellular growth

Sometimes called anti-oncogenes or growth suppressor genes.

They cause cellular transformation if the functional activity of both alleles is LOST

Main examples are the retinoblastoma gene (p110RB) and the p53 gene

57
Q

Why do DNA tumor viruses rarely produce tumors in the natural host?

What are the exception?

A

They rarely produce tumors in the natural host because they lyse permissive cells, and host cells will be permissive. They only transform non-permissive cells, so the cancer occurs in cells that are not the usual host.

Human DNA tumor viruses are the exception

58
Q

Why do RNA tumor viruses produce tumors in the natural host when DNA tumor viruses won’t?

A

RNA tumor viruses will produce tumors in the natural host because unlike DNA tumor viruses, they can transform both permissive and nonpermissive cells

59
Q

Describe how adenoviruses result in cell transformation and cancer.

A

The adenoviruses vary in their oncogenic potential with types 12, 18, and 31 being highly oncogenic.

They transform rodent cells but DO NOT transform human neoplasms (Thank God!)

Because the rat cells don’t have all the necessary replication machinery for adenoviruses, some early proteins are synthesized, but not all (nonpermissive)

They have 2 transforming proteins: E1a and E1b

E1a bind to p110RB (which would usually repress cell proliferation)

E1b binds to p52 (whihc usually turns on p10RB to repress cell proliferation)

This allows the cell to do into uncontrolled proliferation

60
Q

Describe how papillomaviruses cause cancer.

In what?

How?

A

Types 16 and 18 have a strong association with cervical itnraepithelial neoplasia

THe majority of cervical penile and vulvar cancers contain HPV DNA.

The virus multiplies only in differentiating keratinocytes. In any other cell in the skin layer the virus will not multiply fully and can transform the cells.

The transforming proteins are E6 which binds to p53 and E7 which binds to p110RB

61
Q

Describe how polyomaviruses cause tumors.

In who? How?

A

Types:

BK and JC–tumors in rodents and hamsters

SV-40 - replicate in monkeys, tumors in rodents and hamsters

Polyoma virus replicates in mice, but transform hamsters

transformin proteins: SV-40–a large tumor antigen that has domains that bind to p110RB and p53

62
Q

How does EBV (a herpesvirus) cause tumors?

A

Some herpesviruses are linked to human cancer, including EBV.

EBV usually causes mono, but is linked to Burkitt’s lymphoma and nasopharyngeal carcinoma

viral genome is mostly on episomes

EBNA-2 is a transcriptional transactivator, LMP1, LMP2a, and LMP2b are tyrosine kinases

63
Q

How does HSV-2 cause cancer?

How about CMV (another herpesvirus)?

A

It’s implicated in cervical cancer and CIN.

DNA fragments (including those containing rivonucleotide reductase) can transform cells

CMV does vasically the same thing

64
Q

How does Kaposi’s sarcoma-associated herpes virus cause cancer?

A

Cause Kaposi’s sarcoma and implicated in multiple myeloma.

Contains 16 cellular genes including C-cylin and cytokines

65
Q

How do hepadnaviruses cause cancer?

A

This is Hepatitis B and it causes human hepatocellular carcinoma.

Co-factors include impaired immunity and alcohol associated hepatic cirrhosis.

It produces a viral protein called X protein that interacts with p53

Latency can be VERY long

66
Q

What family of RNA viruses can be tumor viruses?

A

retroviridae

67
Q

RNA tumor viruses can cause transformation by 3 ways:

A
  1. introduction of oncogenes
  2. insertional activation or promoter insertion
  3. transcriptional activation
68
Q

What are some important structural aspects of retroviridae?

A

helical nucleoprotein complex inside an icosahedral capsid which is enveloped

undergoes reverse transcription

genome is always 2 strands of + ssRNA which is then itnegrated into host DNA as DNA

69
Q

What are the three sub famlies of retroviruses? Which one causes cancer?

A

Lentiiruses (HIV is this)

Spuma viruses (foamyvirus)

and Onco viruses

THe onco viruses can have the potential for cancer

70
Q

What are the morphological types of oncoviruses?

A

Type A, B, and C–most are considered type C

71
Q

What is the different between exogenous and endogenous type C onco retroviruses?

A

Exogenous type C viruses behave as infectious agents and when oncogenic mainly cause tumors of reticulendothelial system and hematopoetic systems (leukemia, lymphomas) or connective tissue (sarcomas)

Endogenous type C viruses are in all our cells, which are usually not active and are not pathogenic for the host

72
Q

What are three important viral genes encoding for proteins involved in replication in retroviruses?

A

gag, pol, and env

gag encodes for the core and capsid proteins

pol encodes for the polymerase, reverse transcriptase, and integrase

and pro encodes for the protease

73
Q

WHat are the general steps of retrovirus duplication?

A
  1. a retrovirus is brought into the cell and uncoated in a lysosome.
  2. the two strands of +ssRNA are dumped into the cytoplasm.
  3. The virus brings with it RNA encoding for reverse transcritase and polymerase
  4. RT occurs and you get a dsDNA copy of the RNA
  5. This dsDNA is integrated into the genome by integrase
  6. WHen the host cell replicates, so does the viral DNA
  7. WHen the host genome is transcribed, you get transcription of the viral mRNA (for proteins) and the full length RNA that will be packaged in the virion.
  8. Protease cleaves the polypeptide into the necessary proteins
  9. Everything is packaged into a new virion
  10. Virion buds out of the cell
74
Q

Describe how a virus introduces oncogenes into a cell, thus causing cancer.

A

If the viral DNA is integrated into a host cell chromosome right next to what was an oncogene in some cell, the RNA polymerase can make a mistake and copy the genetic information for the oncogene in addition to the virogenes.

The new virions produced will therefore carry the oncogene (now a v-onc)

If the virion enters a new cell, it integrates its genome (with the oncogene) into the host genome.

When this becomes transcribed and translated, the oncogene product is formed and the cell is transformed.

This is also known as ACUTE transformation because the cell will transform as soon as the v-onc is inserted and transcribed/translated

75
Q

Explain how a non-defective virus differs from a defective virus. How do they differ in their mechanism of transformation?

A

Nondefective viruses will produce infectious progeny virioids. (include mos leukemia viruses and Rous sarcoma virus)

Defective viruses have lost part of an entire virogene which has been replaced by an oncogene.

These differ because defective viruses will require a helper virus for replication because it no longer carries all the virogenes necessary for replication.

76
Q

Explain how viruses cause cancer through insertional activation or promoter insertion

A

This occurs in chromic leukemia viruses and moust mamary tumor virus:

Involves viral promoters and transcriptional enhancers in the LTRs of activated cellular oncogenes.

This occurs when you insert a viral genome into a host genome and it gets inserted right next to a gene sequence that is usualy off, but will cuase uncontrolled proliferation is on.

Because the virogene brings in a promoter with it, the promotion will leak over and you’ll get a product of the oncogene that used to be off.

This is considered a form of CHRONIC transforming viruses because it takes longer for the cancer to develop since it requires the random insertion of the virogene near an oncogene that has been turned off.

77
Q

Explain how viruses will cause cancer through transcriptional activation.

A

This is what HTLV1 and HTLV2 do:

It involves transcativator proteins that jump around trying to activate virogenes that have been inserted int he genome. Sometimes they will make a mistake and activate cellular oncogenes.

THe tax protein in HTLV-1 enhances transcriptino of viral genes and cellular genes like IL-2, IL-3, GMCSF, and IL-2 receptor–all of which are upregulated during cell division.