Herpesviruses Flashcards
What is special about herpesviruses
- cause mainly asymptomatic infections in healthy, young humans
- wide variety, but very host specific -> rarely a zoonosis
- linear dsDNA genome is converted into circular epigenome after infection
- transcription of many genes: 100-200
Name some herpesviruses
- three subfamilies (α, β, γ)
α:
- HSV-1/-2
- VZV (chicken pox)
β:
- HCMV
γ:
- EBV (Eppstein-Barr)
- KSHV
What is common about herpesviruses?
- high seroprevalence (besides KSHV)
- establish latent infection
- disseminated disease in non-immunocompetent
- KSHV and EBV (γ-herpesviruses) are oncogenic
Herpesvirus infection
persistent infection:
- chronic or latent
- latent (no infectious progeny) or lyric (infectious virus production) replication cycle
- virus hides in neurons (HSV-1) or immune cells (HCMV, EBV) as circular genetic elements -> epigenomes
- reactivation:
- poorly understood
- possible environmental triggers like stress
- activate classical signal transduction pathways (kinases)
Herpes Simplex virus
- HSV-1/-2
- α-herpesvirus
- causes „cold sore“ and genital herpes
- watery blisters in skin or mucous membranes
- transmission through body fluids
- hides in neuron cell bodies
Varicella zoster virus
- VZV
- α-herpesvirus
- primary infection induces chicken pox
- latency in ganglia
- reactivation causes secondary infection -> shingles
- 20% of patients develop post-herpetic neuralgia -> chronic pain in nerves/skin for years
Human Cytomegalovirus
- HCMV
- β-herpesvirus
- acute infection often asymptomatic
- infection is mainly controlled by cellular immunity (NK, CD8+)
- reactivation with shedding occasionally possible
- major cause of morbidity in transplant patients
- most common viral infection leading to birth defects
γ-herpesviruses
- EBV and KSHV
- oncogenic
- especially in combination with HIV (Karposi sarcoma was most common cancer in african men)
What is the structure of herpesviruses?
- enveloped virus
- also has capsid (T = 16) -> 161 capsomers
- 12 portal vertex -> entry for dsDNA when packed into capsid (force needed)
(- replication in nucleus)
Is there a herpesvirus prophylaxis?
Yes, two vaccines
- Varivax: attenuated replication-competent vaccine against chicken pox (OKA strain)
- Shingrix: recombinant VZV GP E, protects adults >50 against shingles (90% efficacy)
Name replication inhibitors
purine analogues:
- acyclovir
- ganciclovir
- penciclovir & famciclovir (prodrug)
pyrimidine analogues:
- cidofovir
- brivudin
- foscarnet (non-nucleoside analogue)
Acyclovir in more detail
- against α-herpesviruses
- non phosphorylated analogue
-
tri-phosphorylated form is incorporation into viral DNA
- chain abortion due to missing 3‘-hydroxyl group
- only herpesviral thymidine kinase can monophosphorylate -> highly specific
- cellular kinase can only add phosphate to monophosphorylated acyclovir (viral kinase needed)
resistance: reduced affinity to acyclovir but doesn‘t spread in population
Ganciclovir in more detail
- against α- & β-herpesviruses
- incorporation into growing viral DNA
side effects since it is not as specific:
- cytotoxic to white blood cells
- thrombocytopenia (decrease in platelets)
- fever, headache, hallucinations
- maybe cancerogen/mutagen
Penciclovir & Famciclovir in more detail
- Famciclovir is prodrug of Penciclovir -> longer half life
- same mode of action as Acyclovir
Cidofovir & Brivudin in more detail
- abortion of elongation upon incorporation
- Cidofovir mimics monophosporylated nucleotide -> more side effects since its direct substrate for cellular kinase
- Brivudin needs viral thymidine kinase to be monophosporylated -> like Acyclovir
