Module 10 - Viral Replication Strategies Flashcards

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1
Q

In order to replicate, what must all viruses do?

A
  1. Recognize host cells
  2. Make genome available to host cell machinery
  3. Replicate genome
  4. Make multiple copies of required proteins
  5. Assemble new viral particles
  6. Exit the cell
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2
Q

What is the consequence of viruses having a narrow host range?

A

They can only infect and replicate within specific cells

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3
Q

What determines the host range of a virus?

A

The interactions between viral and cellular proteins

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4
Q

What does the viral attachment protein do?

A

Interacts with the receptor on the host cell to allow entry

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5
Q

How come receptors cannot be eliminated to prevent infections?

A

These receptors are generally essential for the host cell

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6
Q

What is the cellular function of the CD4 receptor?

A

Immune cell interactions

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7
Q

What virus attaches to the CD4 receptor?

A

HIV (Retroviridae)

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8
Q

What is the cellular function of the ICAM-1 receptor?

A

Cell adhesion

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9
Q

Which virus attaches to the ICAM-1 receptor?

A

Rhinovirus (Picornaviridae)

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10
Q

What is the cellular function of the Bgp 1a receptor?

A

Cell adhesion

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11
Q

Which virus attaches to the Bgp 1a receptor?

A

MHV-A59 (Coronaviridae)

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12
Q

What is the cellular function of the CR2 receptor?

A

B-cell activation

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13
Q

Which virus attaches to the CR2 receptor?

A

Epstein-Barr virus (Herpesviridae)

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14
Q

What is the cellular function of the sialic acid receptor?

A

Various functions

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15
Q

Which viruses attaches to the sialic acid receptor?

A

Influenza virus (Orthomyxoviridae)

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16
Q

What is the cellular function of the OmpF receptor?

A

Transmembrane channel

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17
Q

Which virus attaches to the OmpF receptor?

A

T2 (Myoviridae)

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18
Q

What receptor does HIV (Retroviridae) bind to?

A

CD4

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19
Q

What receptor does Rhinovirus (Picornaviridae) bind to?

A

ICAM-1

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20
Q

What receptor does MHV-A59 (Coronaviridae) bind to?

A

Bgp 1a

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21
Q

What receptor does Epstein-Barr virus (Herpesviridae) bind to?

A

CR2

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22
Q

What receptor does Influenze virus (Orthomyxoviridae) bind to?

A

Sialic acid

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23
Q

What receptor does T2 (Myoviridae) bind to?

A

OmpF

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24
Q

What are bacteriophages?

A

Viruses that infect bacteria

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25
Q

What do most bacteriophages uses for attachment?

A

Tail fibers which recognize receptors present on the surface of bacterial cells

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26
Q

What 2 molecules does T2 recognize?

A

Lipopolysaccharide, and the outer membrane protein porin F precursor (OmpF)

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27
Q

What bacteria does T2 infect?

A

K-12 strain of E. coli

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28
Q

What strain of E. coli can T2 not infect?

A

O157:H7 (pathogenic strain)

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29
Q

What proteins are found at the tips of the T2 phage?

A

GP37 and GP38

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30
Q

How was it proven that T2 host range was due to strain specific differences in receptors?

A

The proteins on T2 tail fibers were replaced with proteins from a phage that could infect O157:H7 E. coli

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31
Q

What happened when the proteins on T2 tail fibers were replaced with proteins from a phage that could infect O157:H7 E. coli?

A

The T2 phage could not infect K-12 E. coli, but it could infect O157:H7 E. coli

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32
Q

How do enveloped viruses attach to host cells?

A

By a specific viral protein embedded within the envelope

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33
Q

What viral attachment protein is found in H1N1 influenza virus?

A

HA

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34
Q

What does HA stand for?

A

Hemagglutinin

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35
Q

How does adenovirus attach to a host cell?

A

With a viral attachment protein that extends from the capsid

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36
Q

How does poliovirus attach to a host cell?

A

With a protein that is part of the capsid itself

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37
Q

What do adenovirus and poliovirus have in common?

A

They are both non-enveloped viruses

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38
Q

What virus have scientists used to study strain specificity?

A

MHV

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39
Q

What does MHV stand for?

A

Mouse hepatitis virus

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40
Q

What viruses are related to MHV?

A

SARS coronavirus and MERS coronavirus

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41
Q

How come two strains of mice showed different susceptibility to MHV?

A

They had different protein receptors

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42
Q

Compare the Bgp 1a and Bgp 1b receptor.

A

The two proteins are structurally similar, but differ in amino acid sequences

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43
Q

What is the consequence of the amino acid differences in the Bgp 1 receptor?

A

It changes the conformation, so MHV interacts more strongly with Bgp 1a than Bgp 1b

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44
Q

What must happen after a virus binds to a host cell?

A

The virus or its genome must enter the cell

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45
Q

After an enveloped virus binds to a host cell, what separates the viral genome from the cell?

A

Two lipid bilayers (the viral envelope and the plasma membrane)

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46
Q

What interaction triggers receptor mediated endocytosis of influenza?

A

HA with sialic acid glycoprotein

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47
Q

What method does influenza use to enter the host cell?

A

Receptor mediated endocytosis

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48
Q

What causes the conformational change of HA?

A

Acidification of the viral envelope

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49
Q

What happens when HA changes conformation?

A

It exposes a fusion peptide

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50
Q

What does the fusion peptide do in influenza virus?

A

It helps the fusion of the viral envelope and the endosomal membrane

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51
Q

What happens when the viral envelope fuses with the endosomal membrane?

A

The nucleocapsid is released into the cytoplasm

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52
Q

How does HIV anchor to a host cell?

A

The attachment protein gp120 binds to the CD4 receptor

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53
Q

What happens when gp120 binds to CD4?

A

There is a conformational change in gp120, allowing it to bind to the coreceptor

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54
Q

What happens when gp120 binds to the coreceptor?

A

This causes additional conformational changes, leading to the exposure of a fusion protein on gp41

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55
Q

What is the purpose of gp41 in HIV?

A

It has the fusion protein that helps the fusion between the viral envelope and the plasma membrane

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56
Q

What was the first antiretroviral drug approved by the FDA, and when?

A

Fuzeon in 2003

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57
Q

What does Fuzeon do?

A

It is designed to prevent entry of HIV by preventing fusion

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58
Q

How does Fuzeon work?

A

It binds to gp41, preventing conformational change and fusion

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59
Q

What does entry for non-enveloped viruses require?

A

Direct penetration of cellular membrane by virus particle or genome

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60
Q

Generally, how do non-enveloped viruses enter a cell?

A

Through receptor mediated endocytosis

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61
Q

How does receptor mediated endocytosis work?

A

Virus particles bind to the receptor on the cell surface, leading to endocytosis

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62
Q

What happens when a non-enveloped virus enters a cell through receptor mediated endocytosis?

A

The low pH of the endosome causes a conformational change in the capsid (similar to influenza HA protein)

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63
Q

What happens when the capsid undergoes a conformational change in the endosome?

A

It exposes a pore forming domain that leads to the formation of a hole in the membrane

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64
Q

What is the purpose of the pore forming domain in a non-enveloped virus?

A

It allows the viral capsid or genetic material to enter the cytoplasm of the host cell from the endosome

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65
Q

What type of virus is reovirus?

A

A non-enveloped virus

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66
Q

What part of a bacteriophage enters the host cell?

A

The genome (not the particle itself)

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67
Q

What happens when T4 binds to the receptor?

A

It leads to the contraction of the T4 tail

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68
Q

What is the result of the T4 tail contracion?

A

The tail core pushes through the cell wall, bringing the phage DNA in contact with the plasma membrane

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69
Q

How does the phage DNA in T4 enter the cell?

A

Through the help of a pilot protein

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70
Q

What does the pilot protein do?

A

It binds to the phage DNA, and helps it penetrate the plasma membrane

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71
Q

Where does the viral capsid go in a bacteriophage infection?

A

It remains outside the cell

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72
Q

True or false: plant viruses, like bacteriophages, inject their genome into host cells

A

False: they do not inject their genome

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73
Q

How do plant viruses enter cells?

A

They rely on the help of external forces, such as insects

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74
Q

How do insects help plant viruses?

A
  1. Insects feed on plants, damaging the cuticle and cell wall
  2. When feeding, insects may acquire viruses, and transmit the particles
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75
Q

How come plant viruses rely on external forces to enter cells?

A

Due to the tough cell wall

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76
Q

What is tomato yellow leaf virus?

A

A plant virus

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77
Q

For most mammalian viruses, what is needed to allow for the viral genome to interact with the required host cell machinery?

A

Some form of uncoating

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78
Q

What is the first step of poliovirus uncoating?

A

After binding, the particles undergo a conformational change, resulting in the loss of capsid protein VP4

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79
Q

What happens when poliovirus loses VP4?

A

VP1 can interact with the cell membrane

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80
Q

What does VP1 do?

A

It creates a pore through the cell membrane

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81
Q

How does the RNA in poliovirus get from the capsid to the cytoplasm?

A

It leaves the partially disassembled capsid through the VP1-induced channel

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82
Q

How many different replication groups are there?

A

7

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83
Q

How many DNA replication groups are there?

A

3 (dsDNA, ssDNA, dsDNA using RT)

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84
Q

How many RNA replication groups are there?

A

4 (dsRNA, + ssRNA, - ssRNA, ssRNA using RT)

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85
Q

What is Baltimore classification based on?

A

How the mRNA of different viruses is produced

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86
Q

What is a Class I virus?

A

dsDNA virus

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87
Q

How do Class I viruses make mRNA?

A

By using dsDNA genome as a template

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88
Q

Where does genome replication occur for Class I viruses?

A

Usually in the nucleus of host cells

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89
Q

What is an exception to the genome replication rule for Class I viruses?

A

Pox (replicates in cytoplasm using viral enzymes)

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90
Q

How do Class I viruses replicate the genome?

A

Through host cell DNA-dependent DNA polymerase

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91
Q

What is a Class II virus?

A

ssDNA virus

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92
Q

How do Class II viruses make mRNA?

A

By using a dsDNA intermediate

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93
Q

When does genome replication of Class II viruses occur?

A

As ssDNA gets converted into dsDNA, which serves as the template for more genomes

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94
Q

What is a Class III virus?

A

dsRNA virus

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95
Q

How do Class III viruses make mRNA?

A

From one strand (negative strand) of the ds genome

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96
Q

Where does genome replication of Class III viruses occur?

A

In the cytoplasm

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97
Q

How do Class III viruses replicate the genome?

A

Through viral RNA-dependent RNA polymerase

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98
Q

What is a Class IV virus?

A

ssRNA, positive sense

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99
Q

How do Class IV viruses make mRNA?

A

The genome can be recognized by host ribosomes, and functions directly as mRNA

100
Q

Where does genome replication of Class IV viruses occur?

A

In the cytoplasm

101
Q

How do Class IV viruses replicate the genome?

A

Through viral RNA-dependent RNA polymerase

102
Q

What is a Class V virus?

A

ssRNA, negative sense

103
Q

How do Class V viruses make mRNA?

A

By using viral RNA-dependent RNA polymerase on the genome (serves as template for mRNA)

104
Q

How do Class V viruses replicate the genome?

A

Through viral RNA-dependent RNA polymerase

105
Q

Where does genome replication of Class V viruses occur?

A

In the cytoplasm

106
Q

What is a Class VI virus?

A

ssRNA, uses RT

107
Q

What type of enzyme is RT?

A

RNA dependent DNA polymerase

108
Q

How does a Class VI virus use RT?

A

It converts ssRNA genome into dsDNA, which becomes integrated into the host genome

109
Q

How do Class VI viruses make mRNA?

A

From the integrated dsDNA in the host genome

110
Q

How do Class VI viruses replicate the genome?

A

From the integrated dsDNA in the host genome (make more ssRNA)

111
Q

What is a Class VII virus?

A

dsDNA, uses RT

112
Q

How does a Class VII virus make mRNA?

A

From the dsDNA genome

113
Q

How do Class VII viruses replicate the genome?

A

By using RT on the mRNA

114
Q

How do Class VII viruses use RT?

A

By recreating genomic dsDNA from the mRNA

115
Q

What does the genetic material of DNA viruses resemble?

A

The genetic material of host cells

116
Q

Generally, where does replication of DNA viruses occur?

A

In the nucleus

117
Q

What do DNA viruses use to replicate the genome?

A

Host cell DNA polymerase

118
Q

What do DNA viruses use to produce mRNA molecules?

A

Host cell RNA polymerase

119
Q

What is an example of a typical DNA virus (that replicates in the nucleus)?

A

Papillomaviruses

120
Q

What are certain strains of papillomaviruses strongly associated with?

A

Cervical cancers

121
Q

What is an example of an atypical DNA virus?

A

Poxviruses

122
Q

Why is a poxvirus an atypical DNA virus?

A

It replicates in the cytoplasm, not the nucleus (like most DNA viruses)

123
Q

What type of virus is poxvirus?

A

Class I (dsDNA genome)

124
Q

What proteins do poxviruses bring with them when infecting a cell?

A

Viral RNA polymerase and several transcription factors

125
Q

How is poxvirus mRNA made?

A

From using the viral RNA polymerase in the cytoplasm

126
Q

What happens to the poxvirus mRNA?

A

It gets translated in the cytoplasm

127
Q

What is one key enzyme produced by poxvirus mRNA?

A

A viral DNA polymerase to replicate the genome

128
Q

How does poxvirus replicate its genome in the cytoplasm?

A

One gene it encodes for is a viral DNA polymerase, which replicates the genome

129
Q

What do early genes in poxvirus code for?

A

DNA polymerase and other proteins necessary for genome replication

130
Q

What do late genes in poxvirus code for?

A

Structural proteins needed for capsid and envelope formation

131
Q

In terms of the central dogma, what do cells usually do?

A

Make RNA from DNA

132
Q

In terms of the central dogma, what do cells not usually do?

A

Make RNA from RNA

133
Q

Which protein produces RNA from an RNA template?

A

RNA dependent RNA polymerase

134
Q

For RNA viruses, what does RNA dependent RNA polymerase do?

A

Makes genomic RNA, and mRNA that can be recognized and translated by host ribosomes

135
Q

Where does replication of RNA viruses usually occur?

A

In the cytoplasm

136
Q

What is a retrovirus?

A

A virus that uses RT (Class VI and Class VII)

137
Q

What class of virus is poliovirus?

A

Class IV (+ ssRNA)

138
Q

Where do Class IV viruses get RNA polymerase?

A

It is translated directly from the ssRNA genome

139
Q

True or false: Class IV viruses need to bring RNA polymerase into the cell

A

False: it can be transcribed directly from the + sense ssRNA genome

140
Q

What happens if the poliovirus genome is artificially injected into the host cell?

A

It will still cause the same infection

141
Q

How come injecting the poliovirus genome directly into a host cell will cause the same infection?

A

It is a + sense ssRNA genome, so it can be used directly by the cell

142
Q

What is another name for viral + sense ssRNA?

A

Infectious RNA

143
Q

What is - sense ssRNA used for?

A

A template for the complementary + sense ssRNA (which can be read by the host cell ribosomes)

144
Q

Where do Class V viruses get RNA polymerase?

A

They bring it with them

145
Q

True or false: Class V viruses need to bring RNA polymerase into the cell

A

True: they need it to create the + sense ssRNA from the - sense ssRNA genome

146
Q

What does the ssRNA genome of retroviruses produce?

A

RT

147
Q

What does RT do once an RNA retroviruses enters the cell?

A

It uses the RNA as a template to make a DNA-RNA heteroduplex

148
Q

What happens after RT makes the DNA-RNA heteroduplex?

A

It degrades the original RNA molecule with endonuclease activity, and converts the ssDNA into dsDNA

149
Q

What is the endonuclease activity of RT?

A

RNAse H

150
Q

What happens after RT makes dsDNA?

A

The dsDNA moves to the nucleus, where it is integrated into the genome

151
Q

How is dsDNA integrated into the genome (for retroviruses)?

A

Through the viral enzyme integrase

152
Q

What does integrase do?

A

Integrates viral dsDNA into the host cell genome

153
Q

What is the integrated viral DNA known as?

A

Provirus or proviral DNA

154
Q

What happens once the dsDNA is integrated into the genome?

A

The host cell RNA polymerase transcribes the integrated viral genome, producing mRNA

155
Q

What happens when the full length genomic RNA molecules leave the nucleus (in Class VI viruses)?

A

The viral mRNA is translated in the cytoplasm to produce viral proteins and new viral RNA genomes

156
Q

What can the genome of a bacteriophage be?

A

DNA or RNA

157
Q

How do DNA bacteriophages make new genomic copies?

A

Through the host cell DNA polymerase

158
Q

How do RNA bacteriophages make new genomic copies?

A

By using viral RNA polymerase

159
Q

What type of genome do most RNA bacteriophages have?

A

+ sense RNA genome

160
Q

What do lytic phages do?

A

They replicate and lyse the host cell

161
Q

What is another name for lytic phages?

A

Virulent phages

162
Q

What do temperate phages do?

A

They either insert their genome into host cells, or enter the lytic phase

163
Q

How does the genome of P1 of E. coli exist?

A

As a plasmid in the cytoplasm

164
Q

What type of virus is P1?

A

A temperate phage

165
Q

What does the cell do when it has an integrated viral genome?

A

It continues to replicate the viral genome without production of viral particles

166
Q

What can lambda phage do in E. coli to replicate?

A

It can either lyse the cell, or integrate the genome into the genome of the host cell, and replicate with the host DNA

167
Q

What is a prophage?

A

The quiescent viral genome that exists as either a plasmid or integrated into the host genome

168
Q

What is a lysogen?

A

A cell containing a prophage

169
Q

What happens when linear lambda phage DNA enters the cell?

A

It becomes circular

170
Q

What does circular lambda phage DNA do?

A

It integrates into the viral genome (via integrase enzyme)

171
Q

What is c1 and what does it do?

A

Viral repressor protein that represses cro genes

172
Q

What is cro and what does it do?

A

Repressive protein required for lytic replication

173
Q

What happens if there are high amounts of c1?

A

cro is repressed, and lysogenic phase is maintained

174
Q

How can c1 levels drop in a cell?

A

In response to damage causes by UV light or chemical mutagens

175
Q

What happens when c1 levels drop?

A

The cro protein represses the c1 protein needed to maintain the lysogenic phase

176
Q

What happens if there are high amounts of cro?

A

The proteins for lytic replication are produced, maintaining lytic replication

177
Q

How can lambda phage switch between lytic and lysogenic replication?

A

Based on the relative ratio of the two repressor proteins c1 and cro

178
Q

How do cro and c1 levels change in the cell?

A

In response to the overall health of the cell

179
Q

What does c1 bind to?

A

The cro promoter

180
Q

What does cro bind to?

A

The c1 promoter

181
Q

What happens after a virus makes copies of the viral genome and proteins?

A

New viral particles must assemble and leave the infected cell

182
Q

For assembly, what are many viral components?

A

Self assembling

183
Q

What is the advantage of self assembly?

A

From an energetic perspective, it is fast and cheap

184
Q

How do viral proteins assemble?

A

Around the viral nucleic acid, or inserted into an empty capsid

185
Q

How does TMV assemble?

A

The viral proteins assemble around the viral nucleic acid

186
Q

What must a viral genome have to allow viral proteins to assemble around it?

A

A sequence specific assembly motif

187
Q

What is another name for the sequence specific assembly motif?

A

The packaging sequence

188
Q

How does poliovirus assemble?

A

An empty capsid is partially assembled, and the genome is inserted

189
Q

What does the mechanism of egress depend on?

A

The virus type and host cell type

190
Q

What are the steps for egress of enveloped viruses?

A
  1. Viral proteins are inserted into the host cell membrane
  2. Nucleocapsid migrates to membrane with viral proteins
  3. Budding of nucleocapsid
191
Q

What does budding of the nucleocapsid result in?

A

A lipid bilayer containing enveloped proteins

192
Q

What does the envelope of HIV contain?

A

gp120 and gp41 proteins

193
Q

How do non-enveloped viruses egress?

A

Through lysis of the cell

194
Q

How do bacteriophages egress?

A

They produce specific enzymes to destroy the cell membrane and cell wall

195
Q

How do non-enveloped mammalian viruses egress?

A

The cell becomes unstable due to viral replication (no specific enzymes required)

196
Q

True or false: plant viruses lyse the host cell

A

False: they do not lyse the host cell

197
Q

How do plant viruses egress?

A

They travel from one cell to another through cytoplasmic connections

198
Q

How can plant viruses spread from one plant to another?

A

Through disruption of the cell wall structures by outside forces (insects)

199
Q

How do viruses move towards cells?

A

Via simple diffusion

200
Q

What is E. coli strain O157:H7 associated with?

A

Severe intestinal disorders in humans

201
Q

What is T2ppD1?

A

The altered T2 phage with different tail fiber proteins (to test host range)

202
Q

What did scientists use to study strain susceptibility to MHV?

A

SDS page of the two different receptors

203
Q

How do antibodies block viral infections?

A

They bind to viruses to block the interaction between virus and host cell to prevent attachment

204
Q

What is Maraviroc used to treat?

A

HIV

205
Q

What is another name for Maraviroc?

A

Selzentry

206
Q

How does Maraviroc work?

A

It blocks the interaction between the viral attachment protein and the CCR5 co-receptor by binding to CCR5

207
Q

What types of patients is Maraviroc used for?

A

People already with the virus (to slow down progression) (not for prevention)

208
Q

What type of HIV is Maraviroc ineffective against?

A

Strains of HIV that use CXCR4 co-receptor

209
Q

How does HIV enter the cell?

A

It fuses directly with the envelope (no endosome)

210
Q

What is the structure of the fusion peptide?

A

A short string of hydrophobic amino acids

211
Q

What is meant by a virus being pH-dependent?

A

It relies of the low pH of the endosome to function

212
Q

What is a cuticle?

A

A thick waxy cover to protect the plants

213
Q

What are plasmodesmata?

A

Cytoplasmic connections between plant cells

214
Q

Which types of viruses generally require uncoating?

A

Mammalian viruses

215
Q

Which types of viruses do not require uncoating?

A

Bacteriophages

216
Q

What does PVR stand for?

A

Poliovirus receptor

217
Q

What receptor does poliovirus bind to?

A

PVR

218
Q

What happens when poliovirus binds to PVR?

A

The 160S particle becomes a 135S particle

219
Q

What happens when poliovirus becomes a 135S particle?

A

Lipophilic portions of VP1 and VP4 are exposed

220
Q

Which factors do not inhibit poliovirus replication?

A

Blocking endocytosis, and blocking endosome acidification

221
Q

How does poliovirus RNA likely enter the cell?

A

Through either the plasma membrane or the endosomal membrane

222
Q

What is the result of measuring the kinetics of viral replication?

A

A one-step multiplication curve

223
Q

What can be determined from a one-step multiplication curve?

A

The burst size (average number of progeny viruses released from one cell)

224
Q

What family is SV40 a part of?

A

Polyomaviridae family

225
Q

What is the genome is SV40?

A

Small circular DNA genome

226
Q

What viral proteins unwinds the viral genome for SV40?

A

Large T antigen

227
Q

What happens after the viral genome of SV40 is unwound?

A

Host cell primases and DNA polymerases replicate the genome

228
Q

How does large T antigen facilitate viral replication?

A

By priming the cell towards DNA synthesis

229
Q

How does large T antigen prime the cell towards DNA synthesis?

A

By interacting with cell cycle regulatory proteins

230
Q

What can viruses facilitating DNA synthesis lead to?

A

Immortal cell lines

231
Q

Besides SV40, what other virus can drive the cell towards DNA synthesis?

A

HPVs (Human Papillomaviruses)

232
Q

For polyomaviruses and papillomaviruses, what is responsible for transcription of the viral genes?

A

The host cell RNA polymerase II

233
Q

What happens if + sense RNA is converted into a DNA plasmid?

A

The plasmid becomes infectious

234
Q

What is the purpose of making an infectious plasmid from + sense RNA?

A

Researchers can mutate the plasmid (representing the viral genome), and observe the effect on cells

235
Q

What does HIV cause?

A

AIDS

236
Q

Why were retroviruses initially studied?

A

Their ability to form tumors

237
Q

Who studied the first retrovirus?

A

Peyton Rous in 1911

238
Q

What is the most famous retrovirus?

A

HIV

239
Q

How does HIV assemble?

A

It forms a non-infectious precursor, which is then proteolytically processed to a mature, infectious particle

240
Q

How do protease inhibitor drugs work as antivirals?

A

They block proteolytic processing for proper HIV assembly

241
Q

What is the initial precursor capsid of poliovirus made out of?

A

VP1, VP3, and VP0

242
Q

How is poliovirus processed to become a mature virion?

A

VP0 is cleaved into VP2 and VP4

243
Q

What is the advantage of a segmented genome?

A

It allows for genetic variability

244
Q

What virus has a segmented genome?

A

Influenza (8 - ssRNA)

245
Q

How is the nucleocapsid brought in contact with the membrane for egress?

A

Interactions with amino acids of the tail region with the nucleocapsid

246
Q

What enzyme does T4 make for egress?

A

Lysozyme (break down cell wall)