Lecture 3 Herpes Virus Flashcards

1
Q

Is the herpes virus RNA or DNA?

A

DNA

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2
Q

What is the name of the 3 subfamilies of human herpes with examples

A

Alphaherpesvirinae - skin and brain infections e.g. varicella zoster virus
Betaherpesvirinae - e.g. cytomegalovirus
Gammaherpesvirinae - skin and B lymphocyte infections e.g. Kaposi’s sarcoma-associated herpesvirus

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3
Q

Describe the difference between Herpes virus type 1 and 2

A

Type 1 = cold sores, genital lesions and encephalitis which can lead to blindness (rare) [see slide for images]
Type 2 = genital lesions only

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4
Q

Describe the appearance of Kaposi’s sarcoma-associated herpesvirus

A

Vascular lesion tumours therefore very red (haematomas)

Start at the mouth and spread around the whole body

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5
Q

What are the 2 life cycle stages of herpes

A

Latent

Lytic

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6
Q

Describe the latent life cycle stages of herpes

A

Reversible non productive infection of the sensory neuron of the ganglion tissue
Virus travels along the neuronal axon to neuronal cell body and sits there transcriptionally silent (except
Latency Associated Transcript)

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7
Q

Describe the lytic life cycle stages of herpes

A

normally triggered when immune system is low

Virus entry via attachment/penetration of the cell → Transcription → Genome replication to produce viral DNA → Virus assembly → virus envelopment and release = mature infectious virions

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8
Q

How does genital herpes present?

A

Enters via break in skin/mucosa

Reactivation presents as lesions from virus shreading

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9
Q

What is the management of HSV1 and 2

A

No cure - lifetime disease
Drugs to ensure faster symptoms resolution, lesion healing and decrease virus shredding
Acyclovir, valacyclovir (oral) and famcyclovir (oral)
Not the acyclovir over the counter - this does not work due to low dose

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10
Q

What is the method of action of acyclovir and related analogues

A

Nucleoside analogue of guanosine
Pro drug
When viral thymidine kinase is expressed during viral DNA replication, the viral thymidine kinase recognises the acyclovir = phosphorylates
Celluar kinases further phosphorylate = triphosporylated functional form of drug
Now able to replacing guanosine in viral and cellular = chain termination

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11
Q

Describe the different types of dosing options for genital herpes (figures not needed)

A

First episode = very high dose
Recurrent episode = lower dose than first episode, specific to individual
Recurrent episodes very common = constant treatment

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12
Q

Explain what the need for helicase-primase inhibitors are

A

Acyclovir resistant strains starting to come about

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13
Q

Explain how helicase-primase inhibitors word

A

helicase-primase complex = a collection of enzymes that is involved DNA replication
3 enzymes are DNA Helicase, polymerase and ssDNA-stimulated ATPase activity
Molecule BILS 179 BS inhibits this complexes activity by halting movement of polymerase so replication cannot occur

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14
Q

How is HSV2 transmitted?

A

Sexual contact
Vertical transmission from mother to baby
Infant exposure to HSV in the birth canal at delivery

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15
Q

How does neonatal herpes manifest?

A

skin and eye disease
Encephalitis - cognitive impairment, severe neurological disease
organ dysfunction
Death

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16
Q

How can neonatal herpes be prevented?

A

high dose of acyclovir is given from 36 weeks onwards

Mother has established HSV = C section, forceps avoided

17
Q

What condition does varicella zoster virus cause?

A

chicken pox - childhood

herpes zoster/shingles - adult/elderly

18
Q

Describe what post-herpatic neuralgia is and how is occurs

A

nerve damage caused by herpes zoster
Fewer nerve endings seen = loss of sensory input
nerves in dermatomic area of the skin send abnormal signals to the brain = pain which may persist/reoccur for a long time

19
Q

What is the management of herpes zoster?

A

Acyclovir, valacyclovir (oral) and famcyclovir (oral)
Drugs reduce the incidence of new lesion formation
Accelerates healing and resolves acute pain

20
Q

What is the difference in the thymadine kinase in herpes simplex virus and varicella zoster virus

A

VZV thymadine kinase does not phosphorylate acyclovir as well as herpes simplexes

21
Q

what drug is used to overcome the difference in thymadine kinase in herpes simplex virus and varicella zoster virus and how does it work?

A

Cidofovir - acyclic nuceloside phosphonate = only needs 2 phosphorylation steps to be active
Selectivly inhibits viral DNA polymerase = prevents DNA replication and transcription
Phosphorylation can be by cellular kinase = increases risk of toxicity and so given topically to avoid unnecessary cell death

22
Q

What is ASP2151 and how does it work

A

Treatment option for VZV

Helicase primase inhibitor - increased potency for VZV than acyclovir

23
Q

What are BCNAs and how do they work

A

BCNA = bicyclic pyrimidine nucleoside analogues
BEST treatment for VZV
Phosphorylated in 2 steps by VZV thymidine kinase = incorporates into viral DNA (viral only therefore specific)

24
Q

What can be used to treat the post-hepatic pain from shingles?

A

Opioid analgesia

Tricyclic antidepressants

25
Q

Where in the world is Kaposi’s scarcoma-associated herpes virus most prevalent

A

Africa

26
Q

Describe the life cycle for Kaposi’s sarcoma-associated herpes virus

A

Enters B lymphocytes after initial infection (now latent) → replicates → infected endothelial cells on blood vessels, skin and internal organs
→ transformation of endothelial cells

27
Q

Does acyclovir work on Kaposi’s sarcoma-associated herpes virus

A

No

KSHV thymidine kinase does not phosphorylate acyclovir effectively

28
Q

What is the management of Kaposi’s sarcoma-associated herpes virus

A

Boost immune system via HAART

Conventional cancer chemotherapy - not useful in africa

29
Q

Describe the novel antiviral treatment Bevacizumab for KSHV and how they work

A

Viral protein GPCR, K1 and K15 - these proteins upregulates the vascular endothelial growth factor (VEGF) pathway = angiogensis
Therefore use of VEGF inhibitor Bevacizumab (monoclonal antibody) blocks VEGF-A
Expensive treatment, impractical in Africa

30
Q

Describe the novel antiviral treatment Imatinib (Gleevec) for KSHV and how they work

A

KS tumours express protein c-kit - works in pathway to increase transcription factors, inhibits apoptosis and increases protein production so that the tumour can grow
Therefore Imatinib (Gleevec) inhibits Kit
In clinical trials