Viral Lifecycle - Entry and Exit; Viral Lifecycle - Genome Replication and Protein Expression Flashcards

1
Q

Place the steps of the viral life cycle in order:

Entry
Synthesis of virus components
Genome replication & Transcription
Maturation
Assembly
Adsorption (attachment)
Uncoating
Release

quiz

A
  1. Adsorption (attachment)
  2. Entry
  3. Uncoating
  4. Genome replication and transcription
  5. Synthesis of virus components
  6. Assembly
  7. Release
  8. Maturation
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2
Q

The main determinant of viral tropism is:

-The presence of a specific receptor on a target cell
-The viral envelope
-The host species
-Antibodies
-The viral genome

quiz

A
  • presence of specific receptor on target cell

Viral tropism describes the ability of a virus to attach and enter a host cell. This is determined by the presence of a specific receptor on the cell surface. This receptor is usually a glycoprotein, but can also be a phospholipid or carbohydrate. The receptor interacts/binds to a component of the virus e.g. Capsid protein, or envelope glycoprotein.

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3
Q

Human Immunodeficiency virus (HIV) uses which of the following receptors for entry into Macrophages?

-Sialic acid
-CD4 and CXCR4
-Heparin sulphate
-CD4 and CCR5

quiz

A
  • CD4 and CCR5

Influenza virus uses Sialic acid, and Herpesviruses use Heparin sulphate to attach to target cells. HIV uses CD4 and CXCR4 to enter T-cells, and CD4 and CCR5 to enter macrophages

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4
Q

The following statements about viral entry are TRUE or FALSE?

-Some enveloped viruses fuse at the plasma membrane

-Some enveloped viruses fuse at the nuclear membrane

-Some viruses enter cells by endocytosis

-Viruses directly inject their genomes through the plasma membrane

Quiz

A
  • True
  • False
  • True
  • False

Some enveloped viruses directly fuse at the plasma membrane (e.g. HIV), and some are first taken up into an endosome by endocytosis before fusion can occur (e.g. Influenza virus). Viruses infecting eukaryotes do not directly inject their genomes – Bacteriophage use this mechanism to insert their genomes into bacterial cells.

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5
Q

Fusion of the Influenza virus envelope requires:
(Please select all that are correct)

-An increase in the pH of the endosome
-A decrease in the pH of the endosome
-A conformational change in the viral Haemagluttinin protein
-A conformational change in the viral Neuraminidase protein
-Replication of the viral genome

Quiz

A
  • Decrease of pH
  • change in Haemagluttinin protein

Following endocytosis of the Influenza virus, the pH of the endosome is lowered by pumping hydrogen ions across the membrane. This is a normal process of endosomes. The acidic pH causes a conformational change in the Influenza haemagluttinin protein which brings the viral envelope into closer proximity with the endosomal membrane, allowing fusion to occur and release of the viral genome into the cytoplasm.

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6
Q

Which of the following statements are TRUE or FALSE?

-HIV buds at the plasma membrane

-Influenza virus assembles in the nucleus

-Herpesviruses bud from the nuclear membrane

-Poliovirus assembles it’s capsid around the genome

-Coronaviruses bud into the Golgi

Quiz

A
  • True
  • False
  • True
  • False
  • True

HIV and Influenza virus assemble and bud at the plasma membrane. Influenza has a mechanism to correctly insert eight separate genomic segments into the budding virion. Herpesviruses replicate and assemble in the nucleus and then initially bud out from the nuclear membrane before using the cell secretory endosomes for exit from the cell. Coronaviruses bud into the Golgi before being secreted from the cell. Polioviruses insert their genomes into pre-assembled capsids.

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7
Q

Which of the following statements about HIV maturation is TRUE or FALSE?

-Maturation occurs after virus budding

-Maturation is catalysed by the viral protease enzyme

-Maturation is catalysed by the viral reverse transcriptase

-Immature HIV virions are infectious

-The HIV protease is a target for antiviral drugs

Quiz

A
  • True
  • True
  • False
  • False
  • True

HIV buds from the plasma membrane in an immature form which is non-infectious. The viral protease catalyses changes to the nucleocapsid structure resulting in rearrangements of protein components to produce a mature form of HIV which can infect target cells. The HIV protease is a good target for anti-HIV drugs which results in non-infectious particles being released from cells.

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8
Q

Explain the viral lifecycle

state the steps

A
  1. Adsorption (Attachement): random collision btw viral surface protein and host cell receptor
  2. Entry: virus must find receptors on host cell (ie glycoproteins)
    - can either 1) endocytosis or 2) fuse with plasma membrane
  3. Uncoating: eclipse period (viron cant be detected). 3 places where uncoating happens:
    - 1) at plasma membrane
    - 2) within endosomes
    - 3) nuclear membrane
  4. Genome replication and transcription
  5. Synthesis of virus components
  6. Assembly
  7. Release (and maturation)
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9
Q

How does HIV enter host cells?

A

SU protein on HIV attaches to CD4 on target cell (T cells /macrophages) as well as a chemokine receptor (CXCR4 or CCR5)

CCR5 expressed on macrophages, CXCR4 expressed on T- cells

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10
Q

How does Influenza enter host cells?

A

Virus binds sialic acid on host cell by virus HA, then the low pH of the endosome triggers change in HA which results in viral envelope fusing with endosomal membrane

HA= haemogluttin which is a glycoprotein

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11
Q

How does Polio enter host cells?

Polio is non- enveloped

A

Virus binds to host surface, then in endosome the structure changes to make a pore connecting virus and endosome membrane and RNA released into cytoplasm

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12
Q

How does Adenovirus enter host cells?

A

Attaches to host surface via host integrin and fiber receptor, then in endosome it breaks down its surface molecules and ruptures endosome, then attaches to nuclear pore delivers DNA into nucleus

Gets to the nucleus via microtubules

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13
Q

Where does viral assembly occur?

A
  • Nucleus
  • Cytoplasm
  • Plasma membrane

Plasma membrane is where most enveloped viruses assemble

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14
Q

How does release differ between enveloped and non enveloped viruses?

A

enveloped: budding through plasma membrane
non enveloped: sudden rupture of cell

Release can occur at the same time as assembly

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15
Q

Which part of HIV release has been targetted by anti-viral drugs?

A

The final maturation step for HIV, where protease chops up proteins allowing them to rearrange themselves to become mature

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16
Q

Which viruses use the ER and/or Golgi body for exit?

A
  • Herpes (golgi)
  • Coronavirus (rough ER and golgi)
17
Q

What are the roles of the following polymerases:
DNA dependent DNA polymerase
DNA dependent RNA polymerase
RNA dependent RNA polymerase
RNA dependent DNA polymerase (reverse transcriptase)

A

DNA dependent DNA polymerase: +DNA to dsDNA
DNA dependent RNA polymerase: dsDNA to +mRNA
RNA dependent RNA polymerase: +RNA to -RNA
RNA dependent DNA polymerase (reverse transcriptase): +RNA to -DNA to dsDNA

18
Q

Give examples of viruses with dsDNA, ssDNA, dsRNA, +RNA, -RNA, +RNA-RT

A

dsDNA: Herpes
ssDNA: Parvovirus
dsRNA: Reovirus
+RNA: Picornavirus
-RNA: Influenza A
+RNA-RT: Retrovirus

19
Q

How do DNA viruses facilitate gene expression?

A

Use host machinery for transcription and translation

20
Q

What is the problem with RNA viruses facilitating gene expression? What is the solution?

A

Problem: Difficult because eukaryotic cells dont have RNA dependent RNA polymerase, and only one protein per mRNA

Solution: Polyprotein (polio), multiple transcripts (covid), segmented genome (influenza)

Polyprotein is one big protein that after synthesis is cut into a bunch of smaller functional proteins

21
Q

What aspects of viral replication do anti-viral drugs target? Specifically, which aspects do HIV drugs target?

A
  • Attachment antagonists
  • Inhibit uncoating
  • Inhibit DNA/RNA synthesis
  • Block maturation (like for HIV)
    HIV: HAART blocks fusion, entry, antibodies, reverse transcriptase,