Retroviruses Flashcards

1
Q

What is the basic structure of a retrovirus?

A

+ ssRNA, enveloped

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2
Q

What conferes specificity of infection>

A

Transmembrane glycoproteins that mediate attachment to host receptors

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3
Q

What is carried in a retrovirion?

A

2 copies of + ssRNA, 50 copies of reverse transcriptase and integrase

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4
Q

Where does integration occur?

A

in the long-terminal repeats of several hundred base pairs found at both 5’ and 3’ ends of the RNA

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5
Q

What are the three major coding regions and what do they code for?

A

Gag: core proteins
Pol: reverse transcriptase, integrase and protease (RNase H)
Env: surface glycoproteins - determine viral tropism

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6
Q

How is the genome transcribed?

A

Single polycistronic mRNA transcript –> differential splicing for expression

-can be cleaved by proteolytic ensymes to form several proteins

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7
Q

What are the two main forms of retroviruses?

A

Exogenous: descrete viral particles that are transmitted from host to host
Endogenous: intrinsic part of host genome

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8
Q

What 3 circumstances allow a retrovirus to become an oncogenic virus?

A

1) Incorporate an oncogene into its genome
2) Insertion of viral genome adjacent to a cellular oncogene
3) Transforming cell by expression of transactivating proteins

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9
Q

What non-retrovirus uses reverse transcriptase?

A

HepB virus (partially ds circular DNA) uses RT and RNA intermediates as part of lifecycle

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10
Q

Name the 4 known retroviruses that cause disease in humans

A

Human T-cell leukemia viruses (HTLV I and II): delta retroviruses
HIV-1 and 2: lentiviruses

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11
Q

What is the significance of human endogenous retroviruses (HERVS)?

A

Compse 8% of human genome
Not capable of replication
Indicated in autoimmune diseases

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12
Q

How does HTLV-1 transmission occur?

A

Via infected lymphocytes, not through free virus

Blood transfusion, sexual contact, and vertical via placenta or lymphocytes in breast milk

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13
Q

What is the primary infected cell of HTLV-1?

A

CD-4 T lymphocytes

doesn’t kill the T cells like HIV does; merely causes imbalance between Th1 (way too many) and Th2 cells

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14
Q

How does HTLV1 cause cancer?

A

Poorly understood: does NOT encode an ocogene and doesn’t have constent integration site

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15
Q

What two HTLV-1 genes regulate Tcell proliferation?

A

Tax and Rex: activate expression of IL-2 and IL-2r

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16
Q

What two syndromes are caused by HTLV-1

A

Adult T-cell leukemia

  • only develops in 1% infected individuals
  • Incubation period >30years
  • poor response and prognosis

HTLV-1 associated myelopathy: HAM or tropical spastic paraparesis
-slowly progressive debilitating disease of bran and spinal cord: gait stiffness, spasticity, lower leg weakness and bowel/bladder dysfunction

17
Q

What disease may be associated with HTLV-2

A

Hairy cell leukemia

18
Q

How many groups of HIV-1 are there? how did they arise?

A

4 groups, each from a separate introduction of SIV into humans

M: major (most common, almost all infections in US)
O: outlier (west-central africa)
N & P: extremely rare

19
Q

What is predominant calde of HIV in US?

A

HIV-1 M Clade B

20
Q

Where does HIV-2 occur?

A

West Africa and Caribbean

Slower and more benign clinical progression

21
Q

Name the steps of the retroviral life cycle

A

1) Adsorption
2) Entry
3) Reverse transcription
4) Nuclear Import (doesn’t have to wait for cell to divide)
5) Integration
6) Transcription/RNA export
7) Translation
8) Assembly
9) Budding

22
Q

What are the 2 major viral proteins of HIV involved in attachment and adsorption?

A

gp41: transmembrane
gp120: surface; antigenically variable

23
Q

What is the icosahedral matrix (MA) antigen of HIV?

A

p17

24
Q

What is the capsid antigen of HIV?

A

p24 (CA protein)

25
Q

How many transactivating gene regulators are encoded by HIV?

A

7 vpu, vpr, nef, tat, rev, vif and nef

26
Q

What 2 HIV surface proteins interact with host cell receptors?

A

gp120, gp41

27
Q

What is the primary host cell receptor for HIV and where is it present.

A

CD4

T and B cells, macrophages, microglial cells (macrophage derived)

28
Q

What are the two major coreceptors for HIV?

A

CCR5 and CXCR4 (chemokine receptors)

CCR5: binds gp120
-normally receptor for RANTES< MIP1a and b from macrophages

CXCR4 normally binds SDF-1 from stromal cells in lymph nodes and epithelial cells

29
Q

What is the dominant coreceptor?

A

CCR5, M-tropic (macrophage)
955 of new infections

**As course progresses, viruses evolve to become T-tropic, CXCR4 viruses

30
Q

Describe molecular mechanism of entry for HIV

A

1) Virus attaches to CD4 via gp120
2) Conformation change in V3 loop of gp120
3) Coformation change exposes co-receptor binding site
4) Binding of gp120 to CCR5 or CXCR4
5) Exposure of fusion domain of gp41
6) ph-independent conformation change in gp41: fusion of cellular and viral membranes with injection of the viral core into the cyoplasm

31
Q

What family of retroviruses is used in labs?

A

Gammaretroviruses

32
Q

What step in HIV life cycle do drugs targets always precede?

A

Integration: want to target early stages

33
Q

What anti-viral drug targets entry phase?

A

Fusion inhibitor T20

34
Q

Mutation in what gene makes people virtually immune to HIV infection?

A

CCR5 delta 32

35
Q

What drugs target reverse transcription?

A

Block DNA Chain: AZT, tenofovir

Stop reverse transcriptase: nevirapine, efavirenz

36
Q

Current targets for antiretroviral therapy?

A
Fusion
Reverse Transcription
Protease
Integration (integrase)
CCR5 Co-receptors