Lecture 26-27

Question 1

What are the five patterns of infection?

Answer 1

Acute, Persistent, Latent, slow and transforming infections

Question 2

What occurs in the pattern of acute viral infections?

Answer 2

There is a virus that rapidly kills cells and leads to either self-limiting or lethal disease, there is also transient viraemia resolved by the immune system with lasting protection

Question 3

What occurs in the pattern of persistent viral infection?

Answer 3

The viral infection is typically non-cytopathic, with a constant, high level of viral replication reached that will not be spontaneously resolved

Question 4

What occurs in the pattern of latent viral infection?

Answer 4

There is a dormant viral infection with episodic reactivation this typically has an initial cytopathic infection until the virus moves to an new site to become latent

Question 5

What are transforming infections?

Answer 5

When a virus infects a cell and causes it to become oncogenic

Question 6

What occurs in the slow pattern of viral infection?

Answer 6

The initial viral infection is cleared however there are intermittent increases in viral load leading to a long gradual increase in viraemia which will eventually defeat the host

Question 7

What is an example of a virus that has an acute pattern of infection?

Answer 7

Influenza

Question 8

What is an example of a virus that has a persistent pattern of viral infection?

Answer 8

Hepatitis B and C

Question 9

What is an example of a virus that has a latent pattern of viral infection?

Answer 9

Shingles

Question 10

What is an example of a virus that has a slow pattern of viral infection?

Answer 10

HIV

Question 11

What is an example of a virus that has a transforming pattern of infection?

Answer 11

Human Papilloma Virus

Question 12

How does cytopathic virus infection kill the infected cell?

Answer 12

There may be induction of apoptosis or loss of osmotic gradients causing membrane disruption
This effect is not dependent on virus assembly and can be triggered by the expression of a single virus gene in mammalian cells can replicate the cytopathic effect such as rotavirus NSP4 or Poliovirus 2BC which code for viroporins

Question 13

What are viroporins?

Answer 13

General class of virus-encoded protein that share the ability to alter cellular membrane permeability and can therefore lead to osmotic control and cell death

Question 14

What are the two ways in which viruses can cause tumours?

Answer 14

They can introduce an oncogene or they can cause an insertional mutation

Question 15

What are the branches of the immune system?

Answer 15

The innate immune system which is non-antigen specific and the adaptive immune system which is antigen specific and broken down further into a humoral branch mediated by antibodies and a cellular immune system

Question 16

What are the RNA based methods of innate immunity to viral infection?

Answer 16

Dicer can cleave the double stranded RNA of some viral genomes, and then allow the cleaved segments to bind to RISC which can target viral mRNAs for degradation

Question 17

What are the protein-based methods of innate immunity to protect the cell against viral infection?

Answer 17

TLRs use MYD88 and a RIG-I/MAVS complex from the mitochondria both activate the transcription factors NFkappaB and IRF which stimulates IFN production leading to ISG production

Question 18

What is the difference between innate antiviral proteins and intrinsic antiviral proteins?

Answer 18

Intrinsic antiviral proteins are constitutively expressed in the cell where they limit virus replication
Innate antiviral proteins are induced following detection of viral infection within the host cells

Question 19

What is TRIM5?

Answer 19

A ubiquitin E3 ligase which blocks replication before transcription by promoting the degradation of the capsid

Question 20

What is tetherin

Answer 20

This blocks the release of new virions from the infected cell by anchoring the virus membrane to the cell membrane and promoting endocytosis leading to endosomal degradation

Question 21

What is APOBEC3G?

Answer 21

An intrinsic antiviral factor against HIV, member of cytidine deaminase family of enzymes leading to it being packaged into HIV virions and released during new round of infection where it edits the Cs to U in HIV and Gs to As causing the formation of premature stop codons

Question 22

What is the function of the viral Vpu protein?

Answer 22

It is used by HIV to block the function of tetherin

Question 23

What is the function of the viral Vif protein?

Answer 23

It is used by HIV to target APOBEC3G for degradation preventing to from interfering with viral replication

Question 24

What are interferons?

Answer 24

A class of related proteins which belong to the cytokine class of proteins. They are secreted acting in an autocrine and paracrine manner signalling through IFN receptors activating interferon stimulated genes which exhibit a wide range of functions in response to infection, inflammation and cancer

Question 25

What is the difference between type I and type II Interferon?

Answer 25

Type I are 17 non-allelic genes in humans which lack introns including 13 IFNalphas and an IFNbeta, omega, epsilon and kappa the alpha and beta can be expressed in all cells
Type II includes IFNgamma which can only be produced by activated T and NK cells

Question 26

How can viral infection lead to IFN production and a protective response by neighbouring cells?

Answer 26

The viral infection triggers IFN induction through commonly recognized molecules like dsRNA. The secreted IFN acts on neighbouring cells to cause transcription of many genes including OAS, RNase L, Mx (GTPase) and PKR

Question 27

What is PKR?

Answer 27

a serine-threonine kinase expressed in a low level by all cells which is enhanced by IFN. It is usually in an inactive from but activated by contact with dsRNA. It can regulate protein translation through phosphorylating eIF-2alpha

Question 28

How can RLRs determine if cells are infected?

Answer 28

RNA viruses can be recognised by RLRs including RIG-I and MDA-5, these are multidomain proteins with N-Terminal caspase recruitment domain (CARD) and RNA helicase domain (DExD/H) and C-terminal repressor domain (RD) these can activate signalling pathways leading to cellular apoptosis

Question 29

How can cells determine if they are infected?

Answer 29

Through the actions of RLRs and TLRs

Question 30

How can TLRs determine if cells are infected?

Answer 30

The recognise various viral components such as TLR 2/4 recognition of viral glycoproteins
TLR 3/7/9 recognition of viral nucleic acids in the endosome
TLR-3 detects dsRNA, TLR 7 detects ssRNA, TLR-9 detects CpG DNA

Question 31

What are the two classes of T cells which participate in the adaptive immune response to viruses?

Answer 31

CD4+ helper cells which recognise the MHCII antigen complex and proliferate to produce cytokines and augment B cell development leading to antibody production
CD8+ Cytotoxic cells which recognise viral antigens in the MHCI complex to destroy infected cells

Question 32

How do protiens come to be presented on MHC I molecules?

Answer 32

The protein is degraded by the proteasome into small peptides which are transported into the ER via TAP. Inside the ER the peptide will bind to the pocket in MHCI which will then be ferried to the cell membrane via the secretory system to allow the peptide to be presented to CD8+ cells

Question 33

How does humoural immunity play a role in viral protection?

Answer 33

Immature B cells which can recognise viral antigens are stimulated to proliferate and differentiate into antibody secreting plasma cells (with a small proportion becoming memory cells). The antibody can then bind to the virion resulting in steric hinderence preventing it from binding to its receptor and becoming infectious

Question 34

What is the role of cytotoxic T cells in viral immunity?

Answer 34

They detect cells which are infected with the virus through displayed epitotes of 8-14 amino acids on MHC-I and destroy them
This defence is not poreprly induced in chronic viral infections and is necessary inorder for the body to overcome infection

Question 35

What are the mechansims through which viruses can evade the immune system?

Answer 35

Inactivation of innate immunity (reduction of interferon
Modifying the effects of normal immune presentation to avoid being detected
Producing antigen decoys
By hiding or being latent

Question 36

How can viruses inactivate IFN production?

Answer 36

Rotavirus produces NSP1 which is an E3 ubiquination ligase which can target IRFs which promote IFN resulting in their degradation

Question 37

How can viruses inhibit MHC trafficking and antigen presentation?

Answer 37

Adenovirus uses E3-p19k to block entry of MHC I into the golgi system preventing its secretion and hiding its antigen from the immune system

Question 38

What is a virus which evades the immune system through the production of decoys?

Answer 38

Hepaptitis B produces decoys of surface antigen

Question 39

How can DNA viruses evade the immune system?

Answer 39

Many DNA viruses have evolved to establish persistent infections through the acquisition of host genes or genes that interact with molecules involved in immune presentation
This results in some viruses like pox viruses being able to establish lifelong infections which are clinically silent unless immunosuppression alters the balance in the favour of the virus