title: Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.
abstract: Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus-induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naïve uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections.
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bloemker
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Sina
authors.initials: S
authors.lastname: Mollerus
authors.affiliation: Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Gibbert
authors.affiliation: Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.affiliation: Division of Immunophysiology, Institute of Physiology and Pathophysiology, Philipps University of Marburg, Germany.
authors.forename: Adriana
authors.initials: A
authors.lastname: Del Rey
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schedlowski
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany. Electronic address: harald.engler@uk-essen.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Engler
mesh_terms: D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D005622:Friend murine leukemia virus / Q000302:isolation & purification*; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D012190:Retroviridae; D012192:Retroviridae Infections / Q000276:immunology / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D013154:Spleen / Q000276:immunology; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000821:virology; D019562:Viral Load
chemical_list: D002395:Catecholamines; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D009638:Norepinephrine
keywords: COMT; Catecholamines; Chemical sympathectomy; Friend retrovirus; MAO-A; Noradrenaline; Retroviral infection; Sympathetic nervous system