Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.
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.
['Bloemker|Dominique|D|', 'Mollerus|Sina|S|', 'Gibbert|Kathrin|K|', 'Dittmer|Ulf|U|', 'Del Rey|Adriana|A|', 'Schedlowski|Manfred|M|', 'Engler|Harald|H|']
D000818:Animals D002394:Catechol O-Methyltransferase D002395:Catecholamines D005260:Female D005622:Friend murine leukemia virus D051379:Mice D008810:Mice, Inbred C57BL D008995:Monoamine Oxidase D009638:Norepinephrine D012190:Retroviridae D012192:Retroviridae Infections D013154:Spleen D013563:Sympathectomy, Chemical D013564:Sympathetic Nervous System D019562:Viral Load
Catecholamines Chemical sympathectomy Friend retrovirus Sympathetic nervous system Retroviral infection Noradrenaline MAO-A COMT