Herpes Viruses Flashcards
Shared morphology of Herpesviruses
- Spherical, enveloped virions
- Highly labile and sensitive to environmental condition such as UV light and detergents
- Icosohedral Capsid surrounded by tegument, a containing protein to deliver to the host cell and RNA.
- Enclosed in an envelope from the host cell membrane during egress
Shared genetic characteristics of herpesviruses
- Linear dsDNA
- During lytic replication: sequential transcription with Immediate Early (IE) 1st followed by Early (E) then Late (L).
- DNA replication in the nucleus via virally encoded DNA polymerase.
- Establish latent infections during which only a small number of genes are expressed.
Subdivisions of herpesviruses
- alpha
- HSV-1
- HSV-2
- VZV/HSV-3
- beta
- CMV
- HHV-6
- HHV-7
- gamma
- EBV (HHV-4)
- Karposi’s Sarcoma/HHV-8
Characteristics of alpha herpesviruses
- (HSV 1), 2 (HSV 2), and (VZV or HHV 3).
- Replicate quickly and lyse infected cells of mucosal epithelial cells (12-24 hours).
- The α herpesviruses are neurotropic:
- establish latent infections @ peripheral nervous system, primarily in sensory nerve ganglia.
- Variable host range.
Characteristics of beta herpesviruses
- owl eye” inclusions on histology
- CMV) (HHV 6), (HHV-7).
- Replicate VERY slowly (80-120 hours).
- Cell lysis does not occur until several days after infection.
- Latency @ myeloid lineage, also possibly endothelial cells.
- Narrow host range (only humans)
- Evidence of germline transmission of HHV-6 due to viral genome integration events
Characteristics of gamma herpesviruses
- (EBV or HHV 4) and(KSHV or HHV 8).
- Narrow host range, restricted to humans.
- Grows VERY slowly, long replication cycle
- In vitro, all ɣ herpesviruses replicate in lymphoid cells and some are capable of lytic replication in epithelial cells, endothelial cells and fibroblasts.
- EBV and KSHV establish latency in, and can transform, B lymphocytes.
- Have Cyclins
Stages of lytic replication cycle
- virus attachment/entry/uncoating
- viral gene expression and genome replication
- viral assembly and egress
Characteristics of herpesvirus attachment/entry
a. Weak association of Virion with extracellular matrixstrong interaction between viral
glycoprotein and cellular receptoràbinding results in conformation change of viral
glycoprotein and fusion of viral envelope with cell membrane.
b. Nucleocapsid transit to nucleus (nuclear pore)
c. Linear viral genome extruded into nucleoplasmàviral genome circulariz
Characteristics of herpesvirus gene expression and genome replication
a. Viral/cellular transactivators stimulate IE gene expressionàtranslation of IE mRNA
b. IE viral proteins activate viral E gene expression/translation=viral genome replication
c. Circularized Genome is template for genome replication generating long concatomerslinked
end to end (Figure 1).
d. Viral DNA polymerase catalyzes new viral DNA synthesis (Figure 2) by synthesizing
new viral DNA in 5’à3’ direction (Figure 2).
Characteristics of herpesvirus virion assembly and egress
L protein synthesis of structural viral proteins including capsid result in packaging and
egress.
b. Expression of capsid proteins in the nucleus cause nuclear viral inclusions seen on
histopathology.
Molecular targets of anti-herpesviral tx
- DNA polymerase inhibitors.
- Prodrugs that are activated by phosphorylation.
- Monophosphorylated by viral kinase (resistant if lack kinase)
- Then converted to triphosphates by cellular kinase.
- Nucleoside analogs = incorporate into the elongating DNA chain and act as terminators.
HSV1/2: target cell, target latent site
- HSV1
- target = epithelial cells
- latent = Trigeminal Ganglion
- HSV2
- target = epithelial
- latent = Sacral Sensor Ganglion
VZV: target, latent site
Epithelial Cells, T-Cells Sensory Neurons
CMV: target, latent site
Epithelial Cells, endothelial cells
Myeloid precursor cells
HHV6/7: target, latent site
T-Cells, B-Cells, myeloid cells?
T-Cells?
