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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Article

Herpes simplex: Host viral protein interactions.

 
 
 

THIS PAGE IS NO LONGER MAINTAINED (Chris Carter 22/10/2010) BUT IS AVAILABLE AT THIS SITE WHERE KEGG PATHWAY ANALYSIS OF THE HUMAN PROTEINS AND VIDEOS OF THE VARIOUS STAGES OF THE LIFE CYCLE ARE AVAILABLE  

 

A database of HSV-1 interacting host proteins: Genes refer to Homo sapiens : Only direct interactions are reported. If inserting a line, do so from the line below the point of insertion, otherwise the new line will be in bold.Current direct interactions ~ 376: Please change if modified. Click on History to see what's new.

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Receptors and carriers

 

Coagulation factors  

 

Haemoglobins  

 

Endocytosis  

 

Retrograde transport to nucleus  

 

Anterograde transport to plasma membrane  

  • APP Involved in fast anterograde transport of Herpes simplex ( squid axon); Major component of viral particles [45]
  • APPBP2 Binds to tegument US11 product [46] and to APP [47]
  • KIF1A Binds to virion UL56 [48] Kinesins  
  • KIF5B Tegument, envelope proteins and viral particles associate with kinesin-1 [49]
  • Tubulins, MAPT :see above
 

Actin , myosin   and keratin   related

 

Other transport (mostly intracellular: endosome  , golgi  , ER , lysosome   )

 

Exocytosis  

  • ANXA1 Virion component [35] Annexins  
  • ANXA2 Virion component [35]
  • ANXA5 Virion Component [35]
  • GAP43 Tegument, envelope proteins and viral particles associate with GAP-43 [49]
  • SNAP25 associates with Tegument, envelope proteins and viral particles [49]
  • SNAPIN Binds to Glycoprotein J [55]
  • TGOLN2 associates with Tegument, envelope proteins and viral particles [49]
 

Intercellular spread    

  • HSV-1 binds to cell junction components [56]
 

HEAT SHOCK PROTEINS   and protein stress : Unfolded protein response  

HSPs can also act as viral receptors [57] [58]

 

METABOLIC

 

Free radical Antioxidant

 

Ubiquitin proteasome and SUMO    

 

Cell cycle related  

 

Immune and defence

 

Cell signalling

 

Mitochondrial

  • Mitochondria, and tegument proteins UL41 and UL46, migrate to perinuclear regions, via microtubules, in infected cells [108]. Large clusters of mitochondria group around the virus [109]
  • TIMM50 Virion component [35]  
  • Mitochondrial DNA Deletion: UL12 deletes mitochondrial DNA [110]
  • SLC25A5 Binds to product of UL47 [111]
  • US3 tegument protein inhibits mitochondrial electron transport [112]  
  • Switch from aerobic to anaerobic glycolysis post-infection [113]  
 

Nuclear import export

 

Nuclear Proteins

 

Chromatin remodelling  

 

DNA Repair , replication, recombination

 

RNA binding splicing and Ribosomal  

 

Host transcription factors binding to the viral genome

 

HISTONES and Other DNA binding  

Histones can also act as surface receptors for bacteria [171] and viruses [172]

 

Translation  

 

Apoptosis  

 

Viral reactivators

  • Activators of the capsaicin   receptor TRPV1 reactivate HSV-1 [205]
  • Cadmium can reactivate the virus in sensory ganglia [206]
  • CASP3 induces and inhibitors reduce reactivation [207]
  • Heat stress activates the virus in PC12 cells [208]
  • Histone deacetylase inhibitors can reactivate the virus in neuronal cells [209]  
  • CREM (ICER) represses LAT expression and reactivates the virus [210]
  • GAL9 knockdown ameliorates antiviral immune responses [211]
  • ICAM1 modifies resistance in mice [212]
  • IL6 can reactivate the virus [91]
  • Morphine can reactivate the virus in mice [213]
  • MMP9 knockdown increases survival in mice [214]
  • NGF deprivation reactivates the virus in vitro [215]
  • 17-beta-estradiol   reactivates the virus via ESR1 [216]
  • Stimulation of cAMP or protein kinase C pathways can reactivate the virus [217]
  • Theophylline, dibutyryl-cAMP and adrenaline can reactivate the virus in neuroblastoma cells [218]
  • Tetrodotoxin   and GABA   increase viral replication in neuronal culture [219]
  • Ultra-violet light can reactivate the cutaneous virus [220] and sunlight is a reactivation factor [221]
  • Stress related glucocorticoids suppress antiviral immunity [222]  
 

Viral inhibitors

  • Arginine   (NO precursor) suppresses viral growth [223]
  • Ascorbic acid   and dehydroascorbic acid   exert antiviral effects [224]
  • CREBZF (Zhangfei) inhibits viral replication [126]
  • PTGS2 : Cyclo-oxygenase 2 inhibition (bromfenac) can inhibit viral reactivation as can aspirin (and ibuprofen in vitro) [225] [226] [227] Indomethacin suppresses viral replication [228]
  • IFNG blocks viral reactivation (per se) [229] or with IFNA and IFNB [230]
  • IFNG induced NOS1 inhibits viral replication [231]
  • IL18 protects mice against viral infection [232]
  • CREB3 (LUMAN: human VP16 homolog) modifies latency and reactivation [233]
  • Lysine has been reported to be of benefit in human infections [234] (no clinical trial to support this)
  • NGF maintains latency in peripheral neurones [235]
  • Nitric oxide   inhibits viral replication [236] via S-nitrosylation of viral proteins [237]  
  • NOS2 knockouts are more susceptible to infection [238]
  • Ouabain   inhibits viral replication [239]
  • Poly-L-Histidine PL-lysine and PL-arginine have been reported to have antiviral properties [240]
  • Retinoic acid inhibits viral replication [241]  
  • Salivary proline-rich proteins (PRB1 e.g.) or cystatins (CST3 eg) bind to viral particles and inhibit replication [242]
  • Viral infection decreases glutathione levels: Glutathione inhibits HSV-1 replication [243]  
  • Vitamin E defficiency but not supplementation affects viral pathogenicity [244]
  • TNFR1 knockout increases viral replication and lethality [245]
  • Humic Acid exhibits viral fusion inhibition for HSV viruses
 

Antiviral plant and other extracts

  • Cajanus Cajan extracts [246]  
  • Carissa Edulis extracts [247]  
  • Curcumin   decreases HSV-1 infectivity [248]
  • Cyanovirin-N displays anti HSV-1 and anti HIV-1 properties [249]  
  • Humic Acid can have viral fusion inhibition activity
  • Neem extracts have antiviral activity in vitro[250]  
  • Extracts of marine alga Symphyocladia Latiuscula possess antiviral activity in vitro and in vivo [251]  
  • Pyridinium formate from coffee has antiviral activity in vitro [252]
  • Resveratrol can inhibit viral replication [253]  
  • Thai medicinal plant extracts including M.oleifera   A.odorata   and V.denticulata   active in vitro and in vivo [254]
 

Diverse

 

Antiviral drugs and treatments  

  • Acyclovir and related [260]  
  • Silica gel [261]
  • No vaccine yet: Clinical trials   RSS feed  
 

Human diseases linked to Herpes simplex infection

  • Alzheimer's disease [262] Alzheimer's disease susceptibility genes and Herpes simplex [263]
  • HSV-1 infection in mice causes entorhinal cortex and hippocampal degeneration and memory loss as in Alzheimer's disease [264]
  • Atherosclerosis [265]
  • Bipolar disorder [266]
  • Diabetes Type 2 [267]
  • Multiple sclerosis [268]
  • Parkinson's disease [269]
  • Schizophrenia [270]
 

Genes modifying the risk of HSV-1 infection in Man

References

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  20. The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor. Said, E.A., Krust, B., Nisole, S., Svab, J., Briand, J.P., Hovanessian, A.G. J. Biol. Chem. (2002) [Pubmed]
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  70. The infected cell protein 0 of herpes simplex virus 1 dynamically interacts with proteasomes, binds and activates the cdc34 E2 ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin ligase activity. Van Sant, C., Hagglund, R., Lopez, P., Roizman, B. Proc. Natl. Acad. Sci. U. S. A. (2001) [Pubmed]
  71. Replication-initiator protein (UL9) of the herpes simplex virus 1 binds NFB42 and is degraded via the ubiquitin-proteasome pathway. Eom, C.Y., Lehman, I.R. Proc. Natl. Acad. Sci. U. S. A. (2003) [Pubmed]
  72. Herpes simplex virus UL56 interacts with and regulates the Nedd4-family ubiquitin ligase Itch. Ushijima, Y., Luo, C., Kamakura, M., Goshima, F., Kimura, H., Nishiyama, Y. Virol. J. (2010) [Pubmed]
  73. A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses. Lilley, C.E., Chaurushiya, M.S., Boutell, C., Landry, S., Suh, J., Panier, S., Everett, R.D., Stewart, G.S., Durocher, D., Weitzman, M.D. EMBO. J. (2010) [Pubmed]
  74. Herpes simplex virus 1 ICP0 co-localizes with a SUMO-specific protease. Bailey, D., O'Hare, P. J. Gen. Virol. (2002) [Pubmed]
  75. Characterization of the novel E3 ubiquitin ligase encoded in exon 3 of herpes simplex virus-1-infected cell protein 0. Hagglund, R., Roizman, B. Proc. Natl. Acad. Sci. U. S. A. (2002) [Pubmed]
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