Viruses and Infection (1)

Question 1

What are the basic steps in viral replication?

Answer 1

Attachment
Entry
Uncoating
Biosynthesis
Assembly
Exit

→ viruses are obligate intracellular parasites - can only replicate in other cells

Question 2

What can virus encounters lead to?

Answer 2

Various outcomes

In cells:
→ acute cytopathic (kills the cell) infection, persistent infection, latent infection, cell transformation, abortive infection, null infection

In organisms:
→ acute infection (disease), subclinical infection, persistent/chronic infection, latent infection, slowly progressive disease, virus-induced tumour

Question 3

What is a symptom vs a clinical sign?

Answer 3

Symptom: any subjective evidence of disease or of a patients condition
→ usually described by the patient

Clinical sign: an objective physical finding discovered by the examiner

Question 4

What is virulence?

Answer 4

The capacity to cause disease
→ can range from avirulent to lethal
→ different strains of a virus can vary in virulence

Question 5

What is attenuation?

Answer 5

The reduction in the virulence of a virus
→ you can attenuate viruses (i.e. for vaccines)

Question 6

What is pathogenicity?

Answer 6

The ability of the virus to cause pathology: this can be microscopic or macroscopic
→ some avirulent viruses can be pathogenic - the terms are not synonymous

Question 7

What does virulence depend on?

Answer 7

A combination of viral and host factors - different outcomes of infection

Virus factors:
→ strain/isolate - genetically determined differences in sequence
→ dose - high dose usually more virulent
→ route of infection - directly into bloodstream bypasses barriers

Host factors;
→ species
→ genetic constitution - e.g. MHC proteins expressed
→ age, sex, nutritional status

Question 8

What is the Iceberg Principal of Infection?

Answer 8

Death of host and classical/severe illness just the tip of the iceberg
→ below there is mild illness, subclinical/silent infection and no infection

Overall, only a minority of infections result in severe/classical illness

Question 9

How does the immune system control virus infections?

Answer 9

1. Barrier defences → skin, gastric acid, mucous etc.
2. Innate immunity → fast acting. non specific, involving: neutrophils, macrophages, dendritic cells NKC, interferons, cytokines, chemokines
3. Adaptive immunity → slow acting, specific, involving: T lymphocytes, CD4+, CD8+, regulatory T cells, B lymphocytes, antibodies

All work together to lead to virus elimination (and memory)

Question 10

How can virus-host interactions dictate the outcome of infection?

Answer 10

The way the body responds to infection and how the virus counters it impacts outcome e.g.
→ virus dominates over IS: replication & spread of virus, v likely disease
→ IS dominates over virus: limited viral replication, little if any disease
→ extreme IS response: limited viral replication, v likely disease
→ balance of virus with IS: some replication & spread of virus, maybe disease

Question 11

What are type 1 interferons?

Answer 11

Type 1 interferons α and β
→ closely related proteins made in response to viral infection
→ have antiviral activity
→ can upregulate expression of proteins that are antiviral
→ can upregulate expression of MHC I proteins (builds adaptive response)

Question 12

What are type 2 interferons?

Answer 12

Type 2 interferon γ
→ cellular proteins made by activated T cells in response to their cognate antigen
→ is a cytokine
→ different in sequence from type 1 interferons
→ has antiviral activity
→ can upregulate expression of MHC I and II proteins

Question 13

How are type α and β interferons induced?

Answer 13

Detected by either TLR on host cells or RIG-I and mda 5 can recognise viral RNA

These stimulate signalling pathways - stimulate synthesis of interferons
→ phosphorylate IkB → NFkB transcription factor binds to INF promoter
→ phosphorylate IRF3/7 → dimerisation → translocation → binds to INF promoter

Question 14

How do type α and β interferons prime an antiviral state?

Answer 14

Type I interferons produces by an infected cell bind to interfering receptors on the same cell they’re produced by and cells in the vicinity
→ triggers phosphylation of STAT proteins
→ bind to IRF9 and stimulate the production of ISGs (interferon stimulated genes)
→ ISGs can detect the virus

Question 15

What does the antiviral state promote when virus is present?

Answer 15

Apoptosis
→ ISGs include multiple pro-apoptotic factors
→ stops viral replication, stops spread of virus

Question 16

What is the overall innate response to viruses?

Answer 16

Virus infection → Synthesis of type I interferons → Binds to IF receptors → Stimulate synthesis of IF stimulated genes → Prime cell in antiviral state → Virus detection - IF stimulated gene products → Inhibit protein synthesis → Apoptosis → Can’t act as host for virus

Question 17

How can antibodies effect viruses?

Answer 17

Antibodies to virus surface proteins can have a variety of effects on virus infectivity/infection

Neutralising antibodies → bind to virions and neutralise - destroy infectivity
→ aggregate virus particles together or act on early virus-cell interactions (e.g. inhibit endocytosis)
No-neutraising antibodies → bind to virions - can have no effect or prevent binding of neutralising antibodies
Neutralising or non-neutralising antibodies → can bind virus or infected cells and activate complement or act as ligands for Fc receptors on phagocytic cells
→ can enhance infectivity - antibody-dependant enhancement (e.g. dengue)

Antibodies to a virus are not all equal in their effects

Question 18

How do cytotoxic T cells and viruses interact?

Answer 18

Cytotoxic T cells recognise antigenic peptides presented by MHC Class I
→ specificity determined by T cell receptor
→ recognition can lead to - target cell death through delivery of perforin granzyme and inhibition or virus growth by local release of inhibitory cytokines
→ essential for learning viral infection
→ a given virus will present different T cell epitopes in different individuals