Lecture 27 - Herpes Flashcards Preview

MIIM20002 - Microbes, Infections, Responses > Lecture 27 - Herpes > Flashcards

Flashcards in Lecture 27 - Herpes Deck (59):
1

Describe the onset of viral STIs

Acute, but persistent

2

Are symtoms always seen in viral STIs?

No
Can be asymptomatic

3

Under what circumstances are people more susceptible to STIs?

If they already have another STI

4

Why are viral infections so common in the community?

Viruses are persistent in infected cells

5

Describe how viruses are transmitted

They are labile, so they aren't present in the environment

They need person-person contact
• sexual contact
• birth
via sharing of fluids:
• saliva
• vesicular fluid

6

What allows viruses to be so persistent?

Evade immune system

Passive:
• hide in nerves

Active:
• inhibit activity of CTLs and antibodies

7

What is the herpes family of viruses?

Herpesviridae

8

Describe the structure of herpesvirus

Icosahedral
Enveloped
Tegment
Glycoproteins

9

Describe the genome of herpesviruses

ds DNA
Linear
Large genome

10

What sort of proteins does the herpes viruses make?

Wide range:
• enzymes
• structural
• immune evasion proteins

11

Which types of herpes can remain latent in the host?

All of them

12

What are some of the members of the herpesviridae family?

VZV: Varicella zoster
EBV: Epstein-Barr virus, Glandular fever
HHV-6: roeola infantum
HHV-8: Kaposi's sarcoma

13

Are herpes viruses common in the population?

Yes
Almost could be considered normal flora

14

What is the tegment?
What is its function?

Large amount of protein under the envelope

Function to evade the immune system

15

What does being enveloped mean for herpes viruses?

Labile in the environment
• sensitive to drying

16

What are the serotypes of HSV?

HSV-1

HSV-2

17

What is different about the two HSV serotypes?

How can we differentiate them in the lab?

Different antigens
Different genes

Differentiate them by:
• PCR
• antigen detection assay

18

What do HSV-1 and HSV-2 cause?

Both serotypes cause:
Localised:
• cold sores
• genital herpes

Disseminated:
• encephalitis
• meningoencephalitis

19

Describe how HSV enters cells and replicated

1. Gets through skin (cut etc.)
2. Multiple glycoproteins bind cell surface receptors
3. Triggering of fusion of envelope with host cell
4. Nucleocapsid released into the host cell and adheres to nuclear membrane, genome enters nucleus
5. Early mRNA transcribed by host DNA pol
6. Early proteins made
7. Late mRNA transcribed and translated into late proteins
8. Self-assembly
9. Release by budding
10. Cell dies

20

Which cells does HSV invade?

Skin and mucous membrane

• Epithelial cells
• Fibroblasts
• Macrophages

21

How can a virus get into the skin to invade?

Damaged skin
Defective keratin layer

22

Which glycoproteins on HSV are important for binding?

gpB
gpC

23

What type of proteins are translated from the early mRNA?

DNApol
Thymidine kinase enzyme
ICP47

24

What is ICP47?

Protein for immune evasion

25

Describe what happens to epithelial cells upon HSV infection

• lots of virus produced
• Cell death → vesicle formation
• Cell-cell spread

26

Why do vesicles form?

Due to the loss of epithelial cells due to cell death

27

Which fluids contain the virus?

Saliva
Vesicle fluid

28

When does meningitis and meningoencephalitis occur?

When the virus spreads to the CNS

This is rare

29

Describe how HSV persists

Once it gets into the CNS

30

Describe the things that HSV-1 causes

• Cold sores
• Gingivostomatitis
• Herpetic whitlow
• Keratoconjunctivitis
• Encephalitis
• Meningoencephalitis

31

What is Herpetic whitlow?

Lesion on the finger of thumb of HSV

32

Describe the things that HSV-2 causes

• Genital herpes
• Neonatal herpes

33

How many people are HSV-2 antibody positive?

12.5-25%

34

How many people are HSV-1 antibody positive?

70-80%

35

Are antibodies for the two HSV serotypes cross reactive?

To some extent

36

How is HSV-2 generally spread?

Genital secretions

37

Describe latency of HSV

1. Spread from epithelial cells to dorsal root ganglia
HSV-1: trigeminal ganglia
HSV-2: Sacral ganglia

2. Episome in ganglia

38

What is an episome?

Circular piece of DNA
Non-replicating

Covaltently closed

39

Describe reactivation of latent HSV

1. Reactivation from ganglia
2a. Spreads from ganglia to CNS
2b. Spreads back to dermatome
3. Damage
(meningitis, meningoencephalitis)

40

Under what conditions will reactivate the virus?

Stress
Menstruation
Immuno-suppresion

41

Describe the outcomes of reactivation of HSV

May be asymptomatic
Meningitis, Meningoencephalitis

Infection of original site, many vesicles

42

Describe what is happening during latency of HSV

• LAT transcribed, but not translated
• some early genes translated
• T cells, cytokines around infection

43

What is LAT?

Latency activated transcript RNAs

44

Is there an immune response occuring during HSV latency?

• Memory T cells (CD4 & CD8)
• cytokines, chemokines

around the neuron

LAT may be the antigen

45

Describe the innate defences induced by HSV

Epithelium produces IFN-beta

1. PAMP-PRR on MFs and DCs
2. MFs and DCs make IFNa
3. IFNa and IFNb protect uninfected cells

1. Influx of NK cells
2. Lyse infected cells

46

Describe the T cell adaptive defences induced by HSV

Both CD4+ and CD8+ induced

Epithelium:
• CTLs clear infection

Dorsal root ganglia:
• ICP47 down regulates MHC I protein expression
• CTLs ineffective

47

What does ICP47 do?

Inhibits MHC I presentation and expression on CTL

Thus, stunts CD8+ action

48

Describe the B cell adaptive defences induced by HSV

In babies:
• maternal antibodies prevent neonatal infection

But, Ab have limited efficacy

49

Can Ab deficient people control HSV infection?

Yes, just as well as Ab normal people

Thus, Ab is not that important

50

Can the immune system clear HSV?

Only in the epithelium

51

Why can HSV evade the immune system in the neurons?

• limited viral protein producion
• ow levels antigen presentation of MHC I (due to ICP47)

52

How is HSV diagnosed?

• PCR: Antigen detection
• Antibody detection

53

What do we see in primary infection?

Much antigen (see this with PCR)

Antibody takes a while to be inducted, but hereafter, it persists

54

Which isotypes of antibody do we see after HSV infection?

IgG
IgM

55

How is HSV treated?

Acyclovir

• Targets thymidine kinase
• guanosine analogue

56

Describe how acyclovir works

1. In virally infected cells, first phosphate group are added to the nucleoside analogue
2. Analogue then added into growing DNA strand
3. Replication halted, because the five membered sugar is missing

57

How do we prevent HSV?

No vaccine yet
• Gloves
• condoms

58

When is an infected person most likely to transmit HSV to another person?
Why?

In their primary infection
Because their viral load is highest in the primary infection

59

What sort of responses will a HSV vaccine need to induce?

B and T cell responses