From: Herpes simplex virus and varicella zoster virus, the house guests who never leave
Sections | Â | HSV-1 | VZV |
---|---|---|---|
Viral | Genes | ~80: 4 diploid (ICP4, 0, 34.5, LAT) | 68: 3 diploid (ORFs 62, 63, 64) |
Genome | Size | ~152kbp | ~125kbp |
G + C content | −67% | −47% | |
Repeats | -Large repeats for both UL and US | -Large on US only; 88.5 bp on UL | |
Isomers | 4 | Mostly 2 with UL region fixed | |
miRNA | From LAT region- role not yet clear | No known miRNAs | |
Viral Proteins | regulation | Regulated Cascade –defined as | Likely similar, but difficult to define experimentally |
Immediate Early differences | Â | Â | |
α, β1, β2, γ1, γ2-six genes (ICP0, ICP4, ICP27, ICP22, ICP1.5, ICP47. | -Three genes reported to date | ||
-All have TAATGARAT motif in IE promoters | -ORF/IE62(ICP4 Eeq) ORF/IE4(ICP27 eq) and ORF/IE63 (ICP22 eq) | ||
-No ortholog of ICP47. | |||
-Only IE62 has TAATGARAT in promoter | |||
Short Region differences | -gD, an essential protein involved in receptor & entry | -No gD, is essential- | |
-gE not required in culture | -gE is key receptor binding protein | ||
 | -Missing several HSV equivalents | ||
Tegument differences | -UL48 (VP16) required in culture: | -ORF10(VP16 Eq) not required in culture: | |
-UL49 not required | -ORF9 (UL49 eq) required | ||
Primary Infection | Route of Infection | Spread through direct contact. | Spread via aerosol and inhalation. |
Location of 1o infection | -Epithelia in mucosa, cornea or in epidermal layers of the skin | -Epithelial and immune cells in respiratory lymphoid tissues, tonsils | |
-Usually no viremia | -Cell associated viremia | ||
-Secondary infection at the sub-dermis | |||
Spread to neurons | -Usually local only | -Systemic across entire neuraxis | |
-Accesses neuronal axon termini in skin | -Same as HSV; may also access neurons during viremia thrugh immune cells | ||
Innate | TLR-2,3,9 respond to infection | Thought to be the same, but not known | |
IFN regulates infection | IFN regulates infection | ||
NO helps retard viral replication | Role of NO not known | ||
ICP0 degrades PML and ND10 proteins | Susceptible to PML caging. | ||
ORF61 modifies ND10, does not degrade PML | |||
Innate and adaptive immunity | Adaptive T cell response | CD4 and CD8 encounter antigen on DCs and respond to infection | -T cells infected by VZV leading to viral spread. |
-CD4 and CD8 T cells are VZV specific | |||
 | DC | Can infect and reduce presentation to T cells by DCs | -Can infect and reduce presentation to T cells by DCs |
Humoral Response | Elicit antibodies against broad viral antigens. IgA, IgG and IgM | -Elicit antibodies against broad viral antigens. IgA, IgG and IgM. | |
-Antibodies are used in high risk patients to treat VZV | |||
-Antibody has less role on control of infection/ latency and reactivation | |||
 | Immune Evasion | ICP47 blocks TAP function. | -Does not block TAP function. |
-Still blocks MHCI and II expression. | |||
-Blocks MHCI by ORF66 kinase | |||
Inhibit IFN responses thru VHS, ICP0, and γ34.5 | -Inhibit IFN responses by IE63, IE62 | ||
-ORF61 blocks NFkB signaling | |||
gC blocks complement deposition | No equivalent activity for gC | ||
Fc binding ability of gE | VZV gE and gI complex to bind Fc | ||
ICP22, Us5, Us3 and LAT inhibit apoptosis by NK and CD8+ cell mediated lysis | ORF63 blocks apoptosis | ||
Models and Neuronal Latency | Animal modeling | -Most animal models replicate virus | -Guinea pig only small natural animal model that replicates virus |
-Most show similar disease to humans | -No natural model of varicella | ||
-No model of reactivated disease | |||
Location of latency | Sensory ganglia, especially trigeminal ganglia | -Most sensory and autonomic ganglia | |
-Distributed across entire neuraxis | |||
Load | Generally higher genome load than VZV | About one magnitude lower genome load | |
Maintenance latency | Â | -Endless Circular episome. | -Endless circular episome. |
-Heterochromatinated state | -Assumed to be Heterochromatinated state | ||
Latent Gene Expression | -Abundant transcripts from LAT region | -RNAs for ORFs 4,21,61,10,29,62,63, and 66. --Reported protein expression is controversial | |
-LATs processed into miRNAs | -ORF63 most often reported as expressed | ||
-LATs block apoptosis | |||
-Rare protein expression without virus | |||
Immune Component | -Drives ganglionic CD8+ immune infiltrate | -No Immune infiltrate yet reported | |
-CD8 may control reactivation events | -Cellular immunity maintains latency | ||
Reactivation and disease | Occurrence | -May Reactivate frequently | -Reactivated disease usually never or once |
-Incidence drops with age | -Incidence rises with age and declining cellular immunity. | ||
-Disease similar to primary infection | -Occurs anywhere on body | ||
-At same site as 1o infection | -Disease clinically different from 1o Infection | ||
Ganglionic Spread | Involves 1 or few neurons | -Usually intraganglionic spread | |
-Large lesions covering a dermatome. | |||
Causes of reactivation | Multiple environmental and physiological factors | -Mainly immune senescence or suppression. | |
 |  | -Environmental and physiological factors may contribute | |
Pain upon reactivation | -Not usually | -Nearly always neurological involvement | |
-Some sensory loss with repeated recurrence | −90% of zoster has pain | ||
-May develop to post herpetic neuralgia |