Lecture 3 Herpes Virus Flashcards
Is the herpes virus RNA or DNA?
DNA
What is the name of the 3 subfamilies of human herpes with examples
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
Describe the difference between Herpes virus type 1 and 2
Type 1 = cold sores, genital lesions, and encephalitis which can lead to blindness (rare)
Type 2 = genital lesions only
Describe the appearance of Kaposi’s sarcoma-associated herpesvirus
Vascular lesion tumors therefore very red (hematomas)
Start at the mouth and spread around the whole body
What are the 2 life cycle stages of herpes
Latent
Lytic
Describe the latent life cycle stages of herpes
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)
Describe the lytic life cycle stages of herpes
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
How does genital herpes present?
Enters via break in skin/mucosa
Reactivation presents as lesions from virus shreading
What is the management of HSV1 and 2
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
What is the method of action of acyclovir and related analogues
Nucleoside analogue of guanosine
Prodrug
When viral thymidine kinase is expressed during viral DNA replication, the viral thymidine kinase recognizes the acyclovir = phosphorylates
Cellular kinases further phosphorylate = triphosphorylated functional form of drug
Now able to replace guanosine in viral and cellular = chain termination
Describe the different types of dosing options for genital herpes
First episode = very high dose
Recurrent episode = lower dose than first episode, specific to individual
Recurrent episodes very common = constant treatment
Explain what the need for helicase-primase inhibitors are
Acyclovir resistant strains starting to come about
Explain how helicase-primase inhibitors work
- helicase-primase complex = a collection of enzymes that are involved in DNA replication.
- 3 enzymes are DNA Helicase, polymerase, and ssDNA-stimulated ATPase activity.
- Molecule BILS 179 BS inhibits this complexes activity by halting the movement of polymerase so replication cannot occur.
How is HSV2 transmitted?
Sexual contact
Vertical transmission from mother to baby
Infant exposure to HSV in the birth canal at delivery
How does neonatal herpes manifest?
skin and eye disease
Encephalitis - cognitive impairment, severe neurological disease
organ dysfunction
Death
How can neonatal herpes be prevented?
high dose of acyclovir is given from 36 weeks onwards
Mother has established HSV = C section, forceps avoided
What condition does varicella zoster virus cause?
chicken pox - childhood
herpes zoster/shingles - adult/elderly
Describe what post-herpatic neuralgia is and how is occurs
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
What is the management of herpes zoster?
Acyclovir, valacyclovir (oral) and famcyclovir (oral)
Drugs reduce the incidence of new lesion formation
Accelerates healing and resolves acute pain
What is the difference in the thymadine kinase in herpes simplex virus and varicella zoster virus
VZV thymadine kinase does not phosphorylate acyclovir as well as herpes simplex
what drug is used to overcome the difference in thymadine kinase in herpes simplex virus and varicella zoster virus and how does it work?
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
What is ASP2151 and how does it work
Treatment option for VZV
Helicase primase inhibitor - increased potency for VZV than acyclovir
What are BCNAs and how do they work
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)
What can be used to treat the post-hepatic pain from shingles?
Opioid analgesia
Tricyclic antidepressants
