Innate defense mechanisms against HSV-1 infection in the target tissues, skin and brain.
Herpes simplex virus type 1 (HSV-1) initiates productive infection in mucocutaneous tissues to cause cold sores and establishes latent infection in the trigeminal ganglia. Under certain circumstances, HSV-1 may cause encephalitis. Here, we compared host innate defenses against HSV-1 in the two clinically relevant tissues, skin and brain, using a unique ex vivo system of organ culture. Upon HSV-1 infection and spread, apoptosis induction was observed in the skin, but not in brain tissues. While the two tissues elicited interferon (IFN-β) response upon HSV1 infection, IFN induction was more robust in the skin compared to the brain. Moreover, antiviral response to exogenous IFNβ treatment was much stronger in the skin compared to brain tissues. This observation was not related to the availability of the IFN receptor on cells' surface. Taken together, our study demonstrates differential innate antiviral responses to HSV-1 infection that may be exploited in future development of selective and tissue-specific anti-viral treatments.
Department of Biochemistry, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Yael
Y
Tsalenchuck
Department of Neurology, Rabin Medical Center, Campus Beilinson, Petach Tikva, Israel.
Israel
I
Steiner
Department of Biochemistry, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. amospa@ekmd.huji.ac.il.
Amos
A
Panet
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000494:pharmacology; D007763:Lac Operon; D051379:Mice; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000276:immunology; D009924:Organ Culture Techniques; D009928:Organ Specificity; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; C507964:IFNAR1 protein, human; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D049452:Green Fluorescent Proteins; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D000212:Acyclovir
Herpes simplex virus type 1; Interferons; Peripheral sensory ganglia