Exam IV: Lecture 14 Flashcards

1
Q

What is the signature of a retrovirus?

A

It uses Reverse Transcriptase

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2
Q

The genetic information of retroviruses alternate from what to what?

A

RNA and DNA

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3
Q

What is a provirus?

A

A retrovirus in a dsDNA version that is integrated into the host genome

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4
Q

Is the integration of retroviruses required for transcription and replication of the genome?

A

Yes

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5
Q

Retroviruses are known to cause 2 diseases in humans. What are they?

A
  1. AIDS via HIV

2. Adult T-cell leukemia via HTLV-1 infection

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6
Q

What would be a good target for antivirals against retroviruses?

A

Reverse trancriptase

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7
Q

How can a provirus lead to cancer?

A
  1. Disrupt tumor suppressor gene
  2. Insert in front of an oncogene
  3. Bring their own v-oncs with them
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8
Q

How long does the insertion of the provirus into the host DNA last? What is the implication of this?

A

It is permanent

Our genomes are littered with retroviruses that have become inactivated

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9
Q

What are retroposons? What can they do?

A

Ancient traces of retroviruses found in the genome of eukaryotes that are no longer infectious
They can insert into different parts of the genome

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10
Q

Is the genome of retroviruses haploid or diploid?

A

Diploid: two copies exist in each capsid

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11
Q

How long is the retroviral genome?

A

7-10 kb of ssRNA

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12
Q

What is a unique feature about retroviral RNA?

A

It is capped and polyadenylated

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13
Q

What are the 4 main genes in the retroviral genome?

A
  1. gag
  2. pro
  3. pol
  4. env
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14
Q

What is the potential “parent” of HIV?

A

SIV in Monkeys which causes Simian AIDS

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15
Q

What is a lentivirus?

A

A virus that is slow to show symptoms and established a lifelong chronic infection
Tropism = macrophages

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16
Q

What does gag do?

A

Capsid protein, structural, groups specific antigens

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17
Q

What does pol do?

A

reverse transcriptase; Rnase and integrase

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18
Q

What does pro do?

A

Protease, required for processing of gag

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19
Q

What does env do?

A

glycoproteins

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20
Q

Talk me through infection of the cell with retrovirus

A

virus enter cell > release genome > enters into nuclues > integration into DNA = provirus > transcription etc

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21
Q

How does HIV enter the cell?

A

gp120 binds to host CD4 > conformation change of gp130 + gp41 > coreceptor reaction with CCR5 (macrophages)/CXCR4(T-cells) + gp41 > virus anchors into the membrane of CD4+ cell > gp41 changes into coiled shape > brings virus and cell membrane together > fusion > entry and uncoating

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22
Q

What is the benefit to be being born without CCR5?

A

Immune to HIV

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23
Q

What cells does HIV infect? What is the implication of this?

A

T-cells/Macrophages > AIDS (autoimmune disorder)

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24
Q

Where does reverse transcription occur after infection?

A

Within a subviral particle in the cytoplasm

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25
Q

Talk me through the process from entry to integration

A

Entry > reverse trancription in subviral particle = produce dsDNA > dsDNA enters nuclues during mitosis = need actively dividing cell > integrates into host chromosome randomly using integrase

26
Q

Talk me through reverse transcription

A

tRNA is packages in the capsid. tRNA contians sequence that is complementary to viral genome > binds to viral genome and serves as primer > reverse transcriptase extend the OH group with DNA nucliotides > RNaseH (H = hybrid) degrades the RNA after the DNA is made > R of 5’ end has homology with the R sequence at the other end so it jumps and starts elongation again&raquo_space; forms cDNA (c = complementary) with repeats on both ends

27
Q

Is insertion stable or unstable?

A

It is stable

28
Q

The retrovirus does not always kill the host cell and can exist as a _____ gene within the host

A

Mendelian gene

29
Q

What contains all of the signals required for transcription?

A

The LTR: includes binding sites, TATAT box

30
Q

Most signals required for transcription are found in which gene segment?

A

U3

31
Q

Transcription of retroviruses always begins where?

A

The 5’ LTR

32
Q

The processes RNA transcript is identical to the genome and can be packed into progeny viruses

A

True

33
Q

Is the rate of transcription of retrovituses high or low?

A
Very high (potential target for drugs)
Another reason for why it would lead to cancer if integrated in front of a oncogene
34
Q

What are the 4 reasons retroviruses induce uncontrolled cell growth?

A

???

35
Q

Does the DNA of retroviruses contain a stop codon? What is unique about this?

A

Yes it does

But the virus can skip the stop codon > mRNA with many genes > polyprotein > proteolytic cleavage

36
Q

What is translational frameshift? How does it happen?

A

The ribosome reads 3 nucleotides at a time > A RNA pseudoknot (before stop codon) can cause the ribosome to slide back and read with a different 3 reading frame > stop codon is no longer the stop codon > ability to create multiple proteins from one simple genome

The pseudoknot is one specific nucelotide?

37
Q

How does the virus acquire its envelope?

A

By budding through the plasma membrane

38
Q

In HIV, distinct capsids are not seen within the host cell, how can this be explained?

A

The capsid comes together just before the virus leaves the cell

39
Q

How is the capsid formed (what 3 proteins are used)? What does it look like?

A

Formed by the assembly of Gag, Gag-pro, and Gag-pro-pol polyproteins
Spherical structure 100nm in diameter

40
Q

What is the final step after the capsid is formed that makes the virus particle infectious?

A

The polyproteins (gag-pro and gag-pro-pol) are cleaved

41
Q

Why are most transforming retroviruses defective?

A

They pick up oncogenes by recombination with a host cell which replaces an essential part of the viral genome

42
Q

What is an example of a disease caused by a v onc?

A

Erythroblastosis (erbB)

Sarcomas

43
Q

HIV1 and 2 belong to what family?

A

Lentivirus family

44
Q

Infection with HIV induces a vigorous immune response that is unable to clear the virus

A

True

45
Q

Why does the lentivirus family contain so many different genes? (3)

A

Splicing
Framsheifing
Fusion protiens

46
Q

Complex retrovirus have more complex genomes

A

True

47
Q

Which is more pthogenic HIV 1 or 2?

A

HIV 1 > the main cause for AIDS in most infected persons

48
Q

Talk me through HIV infection in the clinical sense

A

Does HIV infect CD4+ Tcells and macrophages > primary infection can be asymptomatic or rash/fever/diarrhea/myalgia/nausea/sore throat > immune response is mounted by CD8+ T cells and B cells > reduces amount of virus > symptoms lessen > disease enters clinical latency > large amounts of virus are made by patient in lymph nodes > steady decline of CD4+ cells > AIDS

49
Q

What are 2 important functions of CD4+ T cells?

A
  1. Activate CTLs

2. Activate B-cells

50
Q

Ablation of CD4+ cells results in the establishment of opportunistic infections int he host including fungal, bacterial, protozoa, and viral infections

A

True

51
Q

How low a count of CD4 cells is required to be “full blown AIDS”

A

Less than 200

52
Q

How is HIV/AIDS transmitted?

A

Blood-borne
Sex
Congenital transmission (blood mixing)

53
Q

What are quasispecies?

A

Highly mutated HIV particles that your antibodies can not fight against

54
Q

What are two unique infections a person with AIDs can get?

A
  1. Oral andidiaiases (thrush)

2. Kapozis sarcoma

55
Q

Is there a vaccine for HIV?

A

No

56
Q

What is the best way to prevent HIV?

A

Practice safe sex

Check all blood to make sure it is safe

57
Q

What does HAART stand for? What is it?

A

Highly Active Antiretroviral Therapy

Combination therapy using a multiple inhibitors

58
Q

What are some of the inhibitors seen in HAART? (4)

A
  1. Reverse transciptase inhibitors
  2. Protease inhibitors
  3. Integrase inhibitors
  4. Entry inhibitors
59
Q

Why do you need HAART to treat HIV/AIDs?

A

RNA easily mutates to become resistant to the drug so you have to hit it with multiple

60
Q

What is the hypothetical start to HIV?

A

Sailor in the UK got SIV from apes in Africa after he killed the primate and had blood-blood contact. It is a relatively new virus