Tnni3k Is Cardioprotective in Viral Myocarditis

TL;DR

The Tnni3k gene helps protect the heart from severe inflammation caused by a virus, according to a study in mice.

Contribution

The study identifies Tnni3k and its kinase activity as novel factors in protecting against acute heart inflammation in viral myocarditis.

Findings

Tnni3k knockout mice showed increased cardiac inflammation and macrophage infiltration after CVB3 infection.

A kinase-dead version of Tnni3k also led to elevated inflammation, similar to full knockout mice.

Long-term heart damage was similar between Tnni3k knockout and wild-type mice.

Abstract

The severity of viral myocarditis in humans and mice is variable between individuals. Numerous observations demonstrate the influence of host genetics on disease course, but few genes have actually been identified to have such properties. In past work, mouse strains that are sensitive or resistant to severe disease were used to map the viral myocarditis susceptibility locus Vms1. Here, we demonstrate that Tnni3k, one of the genes within the Vms1 locus, influences the severity of disease following inoculation with coxsackievirus CVB3. Compared to disease-resistant C57BL/6J wild-type mice, strain-matched Tnni3k knockout mice showed higher cardiac inflammation and, in particular, a greater infiltration of macrophages into the heart. Long-term damage associated with viral infection was comparable in mice of both genotypes. Use of a second mouse line engineered with a point mutation to encode a kinase-dead version of Tnni3k showed the same elevated inflammation as the full null. These results identify Tnni3k and its kinase activity as being protective in modulating the acute phase of inflammatory response to CVB3 infection in the heart.

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