Lecture 5: Herpesvirus

Question 1

5 Herpes Viruses

Answer 1

EBV, HSV-1, HCMV, VZV, KSHV

Question 2

Overview

Answer 2

→ asympomatic in immunocompetent
→ latent, chronic infections
→ reactivation possible
→ high seroprevalence
→ host specific, almost no zoonosis
→ 3 famlies (alpha, beta, gamma)
alpha: HSV, VZV
beta: HCMV
gamma: EBV, KSHV → oncogenic

Question 3

Overview of Herpes viruses

Answer 3

HSV
→ persist through hiding immune system

Varicella Zoster Virus
→ Chickenpox, shingles, can be chronic

Human Cetamegalovirus (HCMV)
→ asymtomatic, cellular immunity via NK and CD8+ T cells

EBV, KSHV
→ cancer, lymphoproliferate disorders

Question 4

Herpes Virus genome

Answer 4

→ dsDNA, converted into circular episome
→ high amount of genes transcribed

Question 5

Herpes Virus Capsid

Answer 5

161 capsomers connectee via triple helix
→ one small capsid protein (SCP) per caposmer

Question 6

Vaccines for Herpes

Answer 6

Varivax
→ attenuated targeting Chickenpox

Shingrix
→ rec. protein Varicella Zoster virus glycoprotein E

Question 7

Relevant drug targets

Answer 7

Transcription and Replication Inhibitors

Terminase Inhibitors
UL97 Inhibitors

Question 8

Acyclovir

mechanism

Resistance

3 other drugs

Answer 8

Purine analog
→ tri-phosphorylated acyclovir incorporated into viral DNA
→ only herpesvirus thymidine kinase can monophosphorylate acyclovir
→ cellular kinase can only phosphorylate monophosphorylated acyclovir → specific without side effects

Resistance
→ thymidine kinase mutations
→ rare mutations of DNA polymerase
→ resistant viruses are not so fital
→ Resistance problem in immunocompromised people

even better
→ Ganciclovir also against ß-strains
→ other viral kinase
→ severe side effects
→ but one of few drugs against HCMV

other option
→ Penciclovir, Famciclovir
→ longer half life
→ Famciclovir prodrug converted to Penciclovir

Question 9

Pyrimidin analogs

Answer 9

Cidofovir, Brivulin

→ Cidovir mimics mono-P-nucleotide
→ side effects
→ Brivulin needs viral kinase
→ more specific

Question 10

Non nucleoside inhibitor

Answer 10

Foscarnet
→ pyrophosphate mimic and binds to binding site
→ inhibits HIV RT as well
→ side effects

Question 11

Terminase inhibitor
→ 2 drug

Answer 11

Terminase providing energie for packaging

2 drugs
→ Letermovir
→ poorly understood
→ resistance observed

→ Maribavir
→ target kinase, that mediates final stage of replication and inhibits encapsulation
→ approved
→ reduce activity of -ciclovir

Question 12

Other Replication Inhibitors

Answer 12

Helicase/Primase
→ Amenamevir, Pritelivivir

Question 13

Combination therapy

Answer 13

not yet

Question 14

Therapeutics against y-Herpesviruses

Answer 14

→ different mode of action required to control tumorigenic potential
→ targeting lytic and latent cycle necessary
→ more research required