Herpesviruses

Question 1

Herpesviruses characteristics

Answer 1

dsDNA, enveloped, complex particle

Alpha/Beta/Gamma

acute infections, lifelong latency/persistence

Question 2

Persistence of Herpes

Answer 2

Challenge: permanent confrontation with immune system.

Important in pregnancy and immunosuppression/transplantation.

Alpha: neurotropic
Beta/Gamma: lymphotropic

High prevalence in humans, except for genital transmission (HSV2, HHV8).
Co-evolution with host.

Question 3

Herpes - human

Answer 3

HSV1: herpes labialis
HSV2: genital herpes
Varicella zoster: varicella/chickenpox
Epstein Barr: infectious mononucleosis

Question 4

Herpes Simplex virus

Answer 4

Alphaherpesvirus.
Primary infection during childhood (symptomatic). Recurrent infections in 1/3 of population. Shedding of virus in saliva/stoll also in asymptomatic individuals.

Question 5

Varicella Zoster virus

Answer 5

Alphaherpesvirus.
Transmission by aerosol/droplets. Highly contagious. Starry sky exanthem.
Latency in neurons > reactivation: herpes zoster (shingles)

Question 6

Recurrence, recrudescence

Answer 6

Recurrence: excretion of virus
Recrudescence: excretion of virus, with symptoms

Question 7

HSV genome

Answer 7

VP16: virion transactivator, drives expression of ICP0/4

ICP0/4: major lytic transactivators

LAT: latency ass transcript

Question 8

HSV latency

Answer 8

Persists in body (ganglia), no infectious virus detectable.

Infection: virus duses at axonal termini > only capsid is transported to soma (VP16 released, no lytic cycle)

Question 9

HSV LAT

Answer 9

Latency ass transcript. Reduce viral transcription of key lytic transcripts by miRNAs > genome enters repressed state (chromatin).

Question 10

HSV reactivation

Answer 10

Lytic gene expression program in neurons: activation of chromatinized genome by stress signaling pathways. Virion assembly > transport in axons > lytic infection in epithelium

Question 11

HSV encephalitis

Answer 11

Spreads to CNS in rare cases. High lethality. Possible genetic predisposition in children.

Question 12

HSV immune evasion

Answer 12

Retreat to immunopriviliged sites (CNS/eye, neurons are non-dividing)

Immunevasion of CTLs (block peptide loading, avoid MHC surface expression) and NK cells (downregulation of stress ligands, expression of MHC-like molecules)

Question 13

HSV - immune balance

Answer 13

Immune recognition and evasion are in balance.

Out of balance (immunosuppression) > severe infections

Question 14

Human cytomegalovirus

Answer 14

Primary infections clinically inapparent.
Transmission: blood, breast milk, urine, saliva.
Severe congenital complications in some non-immune mothers.

Question 15

HCMV and immunosuppression ex

Answer 15

Risk for infection in case of: organ transplantation, BM/stem cell transplantation, AIDS

Question 16

Epstein Barr virus

Answer 16

Infectious monnucleosis/Morbus Pfeiffer/kissing disease.
Transmission: salive, sexual contact, blood.
Infect B cells.

Question 17

EBV latency

Answer 17

Establishment of latency in immortalized B cells.

Few viral genes expressed. Latency genes: EBNAV, LMP, EBER.

Question 18

Varicella zoster virus established latency in..?

Answer 18

Neurons.