L12 - RNA virus replication structure Flashcards

1
Q

What is a model RNA virus used to study replication structures?

A

Flock House Virus (FHV), which infects insects.

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2
Q

Why do viruses induce structural changes in host cells?

A

To create specialized compartments that enhance replication efficiency.

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3
Q

What cellular components are involved in virus-induced structures?

A

Cell membranes, the cytoskeleton, and inter-organelle contacts.

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4
Q

What are virus replication factories?

A

Intracellular compartments where viruses replicate and assemble new particles.

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5
Q

What is the role of host factors in virus replication factories?

A

They provide scaffolding and metabolic support for viral replication.

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6
Q

How do viruses manipulate host cells to form replication factories?

A

By altering metabolic and signaling pathways.

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7
Q

Why do viruses use membrane-bound replication compartments?

A

To increase replication efficiency by concentrating substrates and enzymes.

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8
Q

How do these compartments protect viruses from host defenses?

A

They shield viral replication intermediates like dsRNA from immune detection.

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9
Q

What process is spatially coordinated in these compartments?

A

Viral replication, translation, and assembly.

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10
Q

What imaging technique is used to study virus replication factories?

A

Transmission electron microscopy (TEM).

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11
Q

How does TEM help visualize virus structures?

A

It provides high-resolution images of virus-induced cellular changes.

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12
Q

What is a limitation of TEM?

A

It provides static images and requires complex sample preparation.

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13
Q

What high-resolution imaging technique is used for SARS-CoV-2 replication structures?

A

Cryo-electron tomography (Cryo-ET).

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14
Q

Why is Cryo-ET useful for studying virus lifecycles?

A

It allows visualization of viral replication complexes in near-native conditions.

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15
Q

What cellular structures are altered by SARS-CoV-2 replication?

A

Endoplasmic reticulum (ER)-derived double-membrane vesicles.

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16
Q

How many proteins does Flock House Virus (FHV) encode?

A

Four proteins.

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17
Q

What is the advantage of using FHV as a model?

A

Its simplicity allows detailed study of RNA virus replication mechanisms.

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18
Q

Where does FHV replication occur within the cell?

A

On the outer membrane of mitochondria.

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19
Q

What method is used to identify host factors involved in viral replication?

A

siRNA screening

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20
Q

How does siRNA screening help in virus research?

A

It allows systematic identification of host proteins essential for viral replication.

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21
Q

What was discovered about West Nile Virus using siRNA screening?

A

siRNA screening identified host factors essential for West Nile Virus replication, including proteins involved in RNA binding, membrane remodeling, and intracellular trafficking.

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22
Q

What role do RNA-binding proteins play in viral replication?

A

They assist in RNA recruitment and strand synthesis.

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23
Q

Why are cellular chaperones important for viruses?

A

They help in protein folding and complex assembly.

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24
Q

How do viruses manipulate membrane lipids for replication?

A

They enrich specific lipids like phosphatidylinositol-4-phosphate (PtdIns4P) to modify membranes.

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25
Q

What is a DMV in viral replication?

A

A double-membrane vesicle that houses viral RNA synthesis.

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26
Q

How do convoluted membranes (CMs) contribute to virus replication?

A

They serve as sites for viral protein synthesis and processing.

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27
Q

What is a reticulovesicular network (RVN)?

A

An interconnected membrane network supporting RNA virus replication.

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28
Q

How does poliovirus alter the host cell secretory pathway?

A

It hijacks ER exit sites (ERES) to form replication vesicles.

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29
Q

What cellular structure is repurposed for poliovirus replication?

A

The endoplasmic reticulum (ER).

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30
Q

What is the consequence of poliovirus-induced membrane modifications?

A

It disrupts normal protein trafficking and enhances viral replication.

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31
Q

What is the ERAD pathway, and how do coronaviruses exploit it?

A

The Endoplasmic Reticulum-Associated Degradation pathway, which is hijacked by coronaviruses to enhance replication.

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32
Q

What host proteins are affected by ERAD tuning in coronavirus infection?

A

EDEM1 and OS9, which are downregulated to favor viral replication.

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33
Q

How do coronaviruses modify the ERAD pathway?

A

They transform ER-derived vesicles into double-membrane structures housing viral replication complexes.

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34
Q

Where does hepatitis C virus (HCV) replication take place?

A

In a specialized ER-derived membranous web.

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35
Q

What viral proteins are involved in forming the membranous web?

A

NS5A, NS5B, and NS4B.

36
Q

How do host lipids contribute to HCV replication?

A

Enrichment of cholesterol-rich lipid rafts facilitates viral RNA synthesis.

37
Q

What are viral replication structures composed of?

A

Viral replication structures are composed of modified cellular membranes, viral proteins, and host factors.

38
Q

How do viruses reorganise host membranes for replication?

A

Viruses reorganise host membranes by inducing membrane curvature, forming vesicles, and recruiting host lipids.

39
Q

What role does the cytoskeleton play in virus replication?

A

The cytoskeleton provides structural support and helps transport viral components within the cell.

40
Q

Why do viruses target organelles for replication?

A

Viruses target organelles to gain access to lipid membranes, enzymes, and other resources necessary for replication.

41
Q

How do viruses benefit from modifying host organelles?

A

Modifying host organelles provides viruses with a protected environment and access to replication machinery.

42
Q

Which host membranes are most commonly hijacked by RNA viruses?

A

Endoplasmic reticulum (ER), Golgi, mitochondria, and endosomes are the most commonly hijacked membranes.

43
Q

What is the function of viral-induced double-membrane vesicles?

A

Double-membrane vesicles provide a protective environment for RNA replication and shield viral RNA from detection.

44
Q

How do viral replication compartments shield RNA intermediates?

A

Replication compartments sequester viral dsRNA to prevent activation of host immune sensors.

45
Q

What is the advantage of using membrane vesicles for viral replication?

A

Membrane vesicles concentrate replication factors and provide a scaffold for viral enzyme activity.

46
Q

What is the significance of RNA virus replication occurring on membrane surfaces?

A

RNA virus replication on membrane surfaces allows efficient RNA synthesis and avoids detection.

47
Q

How do viruses remodel endoplasmic reticulum membranes?

A

Viruses induce ER membrane curvature and vesiculation to create replication niches.

48
Q

What is the role of autophagy-related pathways in virus replication?

A

Autophagy-related pathways provide membranes that some viruses repurpose for replication.

49
Q

Why do some viruses manipulate lipid metabolism?

A

Lipid metabolism alterations ensure the production of membranes enriched in viral replication factors.

50
Q

How do viral proteins interact with host lipids?

A

Viral proteins bind to and reorganise host lipids to enhance membrane curvature and vesicle formation.

51
Q

What lipid modifications are essential for viral replication?

A

Phosphatidylinositol-4-phosphate (PI4P) and cholesterol-rich membranes are key for viral replication.

52
Q

Which viral families are known for forming replication factories?

A

Flaviviruses, coronaviruses, picornaviruses, and hepatitis C virus all form replication factories.

53
Q

What is the significance of replication factory size and shape?

A

Factory size and shape impact efficiency by controlling diffusion rates of replication components.

54
Q

How do flaviviruses modify intracellular membranes?

A

Flaviviruses create a reticulovesicular network derived from ER membranes for replication.

55
Q

What evidence supports the idea that viruses exploit the ER-Golgi system?

A

Viral replication depends on the ER-Golgi network for vesicle formation and trafficking.

56
Q

Why do RNA viruses concentrate replication machinery in distinct compartments?

A

Concentrating replication machinery in compartments enhances efficiency and minimises host immune responses.

57
Q

How do cryo-electron tomography and electron microscopy complement each other?

A

Cryo-electron tomography provides 3D images, while electron microscopy provides high-resolution 2D images.

58
Q

What are the key differences between single-membrane and double-membrane replication structures?

A

Single-membrane structures are less protected, while double-membrane structures shield viral intermediates.

59
Q

What role does viral RNA localisation play in replication efficiency?

A

RNA localisation in replication compartments ensures coordinated transcription and translation.

60
Q

Why do viral RNA replication complexes require specific host proteins?

A

Host proteins stabilise viral RNA and support replication by providing essential cofactors.

61
Q

What is a viral RNA synthesis compartment?

A

A viral RNA synthesis compartment is a microenvironment dedicated to viral genome replication.

62
Q

What are spherules in viral replication?

A

Spherules are small vesicular invaginations used as replication compartments by some RNA viruses.

63
Q

How do viruses create spherules?

A

Viruses create spherules by modifying host membranes and forming inward protrusions.

64
Q

Which viruses are known to form spherules?

A

Flaviviruses, alphaviruses, and nodaviruses form spherules.

65
Q

Why do spherules have a narrow neck connecting them to the cytoplasm?

A

The narrow neck allows controlled exchange of nucleotides and enzymes with the cytoplasm.

66
Q

What is the role of viral proteases in replication structures?

A

Viral proteases cleave host and viral proteins to remodel replication structures.

67
Q

How does hepatitis C virus manipulate lipid droplets?

A

HCV utilises lipid droplets as a source of membrane material for its replication complexes.

68
Q

What is the function of phosphatidylinositol-4-phosphate in viral replication?

A

Phosphatidylinositol-4-phosphate (PI4P) is a key lipid for maintaining replication vesicle integrity.

69
Q

What role do stress granules play in viral replication?

A

Stress granules sequester viral RNAs, but some viruses counteract this to facilitate replication.

70
Q

How do viruses interact with host stress granules?

A

Viruses can inhibit stress granule formation or dissolve them to ensure efficient RNA translation.

71
Q

What host factors are involved in coronavirus replication vesicle formation?

A

Coronavirus replication vesicles require host proteins involved in membrane trafficking.

72
Q

How does poliovirus disrupt host cellular transport pathways?

A

Poliovirus hijacks the ER-Golgi network and disrupts protein secretion pathways.

73
Q

What is the impact of viral replication factories on host cell function?

A

Replication factories alter host cell metabolism and interfere with normal cellular processes.

74
Q

How do viruses evade immune detection within replication compartments?

A

Sequestering viral RNA in membrane-bound compartments reduces recognition by host sensors.

75
Q

What mechanisms prevent the host cell from detecting viral dsRNA?

A

Viral dsRNA is hidden in vesicles, preventing activation of interferon pathways.

76
Q

How does the replication structure of flaviviruses differ from that of coronaviruses?

A

Flaviviruses form invaginations within ER membranes, while coronaviruses form double-membrane vesicles.

77
Q

What are convoluted membranes, and how do they contribute to viral replication?

A

Convoluted membranes (CMs) are disordered membranous structures associated with viral protein synthesis.

78
Q

Why do some viruses form multi-vesicular bodies?

A

Some viruses form multi-vesicular bodies as part of their exit or replication strategy.

79
Q

What host enzymes are required for viral membrane modifications?

A

Host lipid-modifying enzymes like PI4K and ACBD3 are crucial for replication membrane formation.

80
Q

How does viral genome size influence replication compartment structure?

A

A larger viral genome may require more complex replication structures for organisation.

81
Q

What role do mitochondria play in some viral replication strategies?

A

Mitochondria provide ATP and membrane surfaces for replication of some RNA viruses.

82
Q

How do viruses exploit intracellular trafficking pathways?

A

Viruses exploit intracellular trafficking pathways to transport replication components efficiently.

83
Q

What are the consequences of viral membrane modifications for cellular homeostasis?

A

Altering host membranes affects lipid balance, ER function, and protein secretion.

84
Q

What is the significance of viral replication occurring near ER exit sites?

A

ER exit sites serve as hubs for viral RNA synthesis and vesicle formation.

85
Q

Why do some viruses induce the formation of membrane tubules?

A

Viruses form membrane tubules to increase the surface area available for replication.