Flashcards in Lecture 27 - Herpes Deck (59):
Describe the onset of viral STIs
Acute, but persistent
Are symtoms always seen in viral STIs?
Can be asymptomatic
Under what circumstances are people more susceptible to STIs?
If they already have another STI
Why are viral infections so common in the community?
Viruses are persistent in infected cells
Describe how viruses are transmitted
They are labile, so they aren't present in the environment
They need person-person contact
• sexual contact
via sharing of fluids:
• vesicular fluid
What allows viruses to be so persistent?
Evade immune system
• hide in nerves
• inhibit activity of CTLs and antibodies
What is the herpes family of viruses?
Describe the structure of herpesvirus
Describe the genome of herpesviruses
What sort of proteins does the herpes viruses make?
• immune evasion proteins
Which types of herpes can remain latent in the host?
All of them
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
Are herpes viruses common in the population?
Almost could be considered normal flora
What is the tegment?
What is its function?
Large amount of protein under the envelope
Function to evade the immune system
What does being enveloped mean for herpes viruses?
Labile in the environment
• sensitive to drying
What are the serotypes of HSV?
What is different about the two HSV serotypes?
How can we differentiate them in the lab?
Differentiate them by:
• antigen detection assay
What do HSV-1 and HSV-2 cause?
Both serotypes cause:
• cold sores
• genital herpes
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
9. Release by budding
10. Cell dies
Which cells does HSV invade?
Skin and mucous membrane
• Epithelial cells
How can a virus get into the skin to invade?
Defective keratin layer
Which glycoproteins on HSV are important for binding?
What type of proteins are translated from the early mRNA?
Thymidine kinase enzyme
What is ICP47?
Protein for immune evasion
Describe what happens to epithelial cells upon HSV infection
• lots of virus produced
• Cell death → vesicle formation
• Cell-cell spread
Why do vesicles form?
Due to the loss of epithelial cells due to cell death
Which fluids contain the virus?
When does meningitis and meningoencephalitis occur?
When the virus spreads to the CNS
This is rare
Describe how HSV persists
Once it gets into the CNS
Describe the things that HSV-1 causes
• Cold sores
• Herpetic whitlow
What is Herpetic whitlow?
Lesion on the finger of thumb of HSV
Describe the things that HSV-2 causes
• Genital herpes
• Neonatal herpes
How many people are HSV-2 antibody positive?
How many people are HSV-1 antibody positive?
Are antibodies for the two HSV serotypes cross reactive?
To some extent
How is HSV-2 generally spread?
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
What is an episome?
Circular piece of DNA
Describe reactivation of latent HSV
1. Reactivation from ganglia
2a. Spreads from ganglia to CNS
2b. Spreads back to dermatome
Under what conditions will reactivate the virus?
Describe the outcomes of reactivation of HSV
May be asymptomatic
Infection of original site, many vesicles
Describe what is happening during latency of HSV
• LAT transcribed, but not translated
• some early genes translated
• T cells, cytokines around infection
What is LAT?
Latency activated transcript RNAs
Is there an immune response occuring during HSV latency?
• Memory T cells (CD4 & CD8)
• cytokines, chemokines
around the neuron
LAT may be the antigen
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
Describe the T cell adaptive defences induced by HSV
Both CD4+ and CD8+ induced
• CTLs clear infection
Dorsal root ganglia:
• ICP47 down regulates MHC I protein expression
• CTLs ineffective
What does ICP47 do?
Inhibits MHC I presentation and expression on CTL
Thus, stunts CD8+ action
Describe the B cell adaptive defences induced by HSV
• maternal antibodies prevent neonatal infection
But, Ab have limited efficacy
Can Ab deficient people control HSV infection?
Yes, just as well as Ab normal people
Thus, Ab is not that important
Can the immune system clear HSV?
Only in the epithelium
Why can HSV evade the immune system in the neurons?
• limited viral protein producion
• ow levels antigen presentation of MHC I (due to ICP47)
How is HSV diagnosed?
• PCR: Antigen detection
• Antibody detection
What do we see in primary infection?
Much antigen (see this with PCR)
Antibody takes a while to be inducted, but hereafter, it persists
Which isotypes of antibody do we see after HSV infection?
How is HSV treated?
• Targets thymidine kinase
• guanosine analogue
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
How do we prevent HSV?
No vaccine yet
When is an infected person most likely to transmit HSV to another person?
In their primary infection
Because their viral load is highest in the primary infection