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Microbiology E-Books > Retroviruses > Flashcards

Retroviruses Flashcards

1
Q

RNA viruses that replicate through a DNA intermediate, which efficiently integrates into the genome of permissive cells forming a provirus

A

Retroviruses

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2
Q

A hallmark of the retrovirus life cycle is the process of

A

Reverse transcription

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3
Q

The viral RNA genome acts as template for the synthesis of viral DNA by the virus encoded polymerase during

A

Reverse transcription

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4
Q

Other viruses such as Hepatitis B virus and Cauliflower Mosaic virus utilize

A

Reverse transcription

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5
Q

The study of Retroviruses has taken on added intensity since the discovery of pathogenic human retroviruses such as

A

HIV-1 and 2 and Human T-lymphotrophic virus (HTLV-1)

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6
Q

Cause tumors in animals

A

Oncoretroviruses

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7
Q

Cause a variety of immunological and neurological diseases with a long latency

A

Lentiviruses

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8
Q

Cause vacuolation of some mammalian cells in culture

A

Spumaviruses

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9
Q

Surrounded by a lipid envelope derived from the infected cell upon budding of the virus

-Measure approximately 100 nm in diameter

A

Mature HIV-1 Virion

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10
Q

The virions have spikes emanating from the

A

Envelope

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11
Q

The spikes are composed of virus envelope proteins, which bind to receptors on permissive cells to initiate

A

Infection

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12
Q

The core of mature virions is conical in structure in the case of

A

HIV-1

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13
Q

The core of mature virions contains a round core in the center of the particle in the case of the

A

Murine leukemia virus

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14
Q

There are additional structures that have been observed for other types of retroviruses. But what is common to them all is that the infectious mature virions contain a condensed core of

A

Electron dense material

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15
Q

The genome within the core consists of two usually identical single-stranded, positive strand

A

RNA molecules

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16
Q

The RNA is capped and polyadenylated indicating that it is transcribed by cellular

A

RNA polymerase II

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17
Q

Most of the cis-acting elements that must be covalently linked to the genome for efficient replication to occur are located at the ends of the

A

Genome

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18
Q

The trans-acting sequences encoding the viral proteins are located between the

A

cis-acting elements

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19
Q

The retroviral genome is always organized in the same way as

A

5’ gag pol env 3”

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20
Q

At each end of the proviral genome (integrated double-stranded DNA) are

A

Long Terminal Repeats (LTRs)

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21
Q

The long terminal repeats can be funcitonally divided into which 3 parts?

A

U3, R, and U5

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22
Q

Begins in the 5’ LTR of the provirus at the U3-R border

A

Transcription initiation

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23
Q

It should be noted that the viral promoter is harbored in

A

U3

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24
Q

Occurs in the 3’ LTR at the R-U5 border

A

Polyadenylation

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25
Q

Thus, the single-stranded RNA genome found in virions is shorter than the viral doublestranded

A

DNA genome

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26
Q

The sequence that is lost during RNA transcription is replaced during

A

Reverse transcription

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27
Q

They are typically cell surface proteins with the different groups employing different proteins, as such they are important determinants of host range

A

Retrovirus receptors

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28
Q

A notable retrovirus receptor

-The receptor for HIV

A

CD4

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29
Q

Found on helper T cells and macrophages helping to account for the HIV host range

A

CD4 receptor

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30
Q

In contrast to other retrovirus receptors isolated to date, requires a co-receptor

A

HIV infection

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31
Q

The co-receptors are members of the chemokine receptor family with the most prominent being

A

CXCR4 and CCR5

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32
Q

Infection is initiated when the envelope glycoprotein SU (surface envelope protein) binds to the corresponding receptor(s) on the permissive

A

Target Cell

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33
Q

This initiates conformational changes resulting in direct membrane fusion between the membranes of the

A

Virus and cell

34
Q

This fusion is mediated by the hydrophobic domain of

A

TM

35
Q

After entry into the cell, the process of reverse transcription ensues during which the single-stranded virion RNA is converted into double-stranded DNA by the virus encoded

A

Reverse transcriptase

36
Q

In order to generate the LTRs, RT makes two

-Unusual for a DNA polymerase

A

Strand transfers

37
Q

Can integrate into non-dividing cells indicating that there is an active transport mechanism for the preintegration complex

A

HIV-1

38
Q

On the other hand, other retroviruses integrate during

A

Mitosis

39
Q

Integration occurs relatively randomly throughout the genome with a preference for open chromatin such as

A

Actively transcribed genes

40
Q

Mediated by the virus encoded integrase (IN) and requires cis-acting attachment sites at the ends of the viral genome

A

Retroviral integration

41
Q

During the process of integration, two nucleotides are lost at each end of the unintegrated dsDNA genome and the cellular target sequence is

A

Duplicated

42
Q

The retroviral genome is transcribed by cellular

A

RNA polymerase II

43
Q

The viral transcripts then undergo RNA processing and

A

Transport

44
Q

For all retroviruses at least two mRNAs are produced: 1) a full-length transcript which is translated to yield the

A

Gag and Gag-Pol polyproteins

45
Q

For all retroviruses at least two mRNAs are produced: 2) a singly spliced mRNA, which encodes the

A

Env polyprotein

46
Q

However, this represents the simplest splicing pattern as exemplified by

A

Moloney murine leukemia virus

47
Q

Has a more complex splicing pattern because in addition to the expression of Gag, Pol, and Env, it encodes a number of other proteins translated from alternately processed transcripts

A

HIV-1

48
Q

The gag and pol genes are usually in different translational reading frames, yet both are translated from the same unspliced

A

Viral mRNA

49
Q

Most of the time just the Gag polyprotein is translated, but a percentage of the time (e.g. for HIV-1 about 5%) a larger Gag-Pol polyprotein is synthesized owing to

A

Translational frameshifting

50
Q

One notable exception to translational frameshifting is in the case of MLV in which there is a stop codon between the

A

Two genes in the same reading frame

51
Q

Again RNA secondary structure seems to play an important role in suppressing the stop codon in the case of

A

MLV

52
Q

Once translated the Gag and Gag-Pol polyproteins are transported through the cytosol to the inner cell membrane where assembly takes place for most

A

Retroviruses

53
Q

The polyprotein is proteolytically processed by the virus encoded

A

Protease

54
Q

Translated from a singly spliced viral mRNA

A

Envelope glycoproteins

55
Q

The Env polyprotein matures in the

A

Secretory pathway

56
Q

It has a signal peptide for cotranslational insertion into the endoplasmic reticulum (ER), and there is a hydrophobic domain, which anchors it to the membrane

A

Env polyprotein

57
Q

In the ER processing begins including significant glycosylation followed by transport to the

A

Golgi complex

58
Q

Here, a cellular protease further cleaves Env polyprotein into

A

SU and TM

59
Q

This distinguishes it from Gag and Gag-Pol processing, which is carried out by the

A

Viral protease

60
Q

Remain associated via noncovalent interactions

A

SU and TM

61
Q

For most retroviruses, assembly and budding occur at the

A

Cell surface

62
Q

The Gag and Gag-Pol polyproteins have been targeted to the cell surface through the

A

Cytosol

63
Q

Once all of the virus components are localized to the cell membrane, we see

A

Assembly into virions

64
Q

Budding then ensues with subsequent viral maturation when the virus protease cleaves the

A

Gag and Gag-pol polyproteins

65
Q

This produces the mature and infectious

A

Virion

66
Q

Regulation of processing is controlled because protease is only active as a dimer, so it only becomes active

A

Post-assembly

67
Q

Most retroviral vectors used for gene therapy trial have been derived from the simple

A

Murine Leukemia Virus (MLV)

68
Q

A common strategy used for making the system safer is to separate the

A

Cis-acting and trans-acting sequences

69
Q

The gene(s) that you want to transfer is placed into a transducing vector, which contains the

A

Cis-acting sequences

70
Q

However, the transducing vector has deletion of some or all of the

A

Trans-acting sequences

71
Q

A packaging cell is needed in order to propagate the

A

Vector virus

72
Q

This cell expresses the genes encoding the viral protein using non-retroviral signals to direct their

A

Expression

73
Q

The transducing vector, in the form of plasmid DNA, is introduced into the packaging cell, where the vector virus RNA is transcribed and packaged into

A

Vector virions

74
Q

The vector virus buds from the packaging cell and can be used to target the cells of

A

Interest

75
Q

Since the vector virus does not encode the viral proteins, the vector can integrate into the genome of the target cell but can not produce

A

Progeny virus

76
Q

Recent trials that exemplify both the potential benefit and the risk of gene therapy are those involving the treatment of

A

Severe Combined Immunodeficiency (SCID)–X1

77
Q

SCIDs are a series of genetic disorders in which T-cell differentiation is arrested resulting in severely impaired

A

Immunity

78
Q

Ten different molecular defects have now been identified, all of which lead to early death in the absence of

A

Therapy

79
Q

Transplantation of MHC compatible hematopoietic stem cells can restore T-cell development and rescue the lives of

A

SCID patients

80
Q

An X-linked disease

A

SCID-X1

81
Q

Contains early progenitor cells that can repopulate the lymphoid lineage

A

CD34+ population

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