Lack of GPAT1 enhances the pathology associated with coxsackievirus B3 infection in mice

Abstract

The mitochondrial isoform of glycerol-3-phosphate acyltransferase (GPAT-1) has been shown to be important in the synthesis of triacylglycerol and in the placement of saturated fatty acids at the sn-1 position of phospholipids. A mouse deficient in GPAT1 (GPAT1−/ −) demonstrated altered composition of liver phospholipids and elevated oxidative stress. Previous research in our laboratory demonstrated that coxsackievirus B3 (CVB3) infection can be exacerbated by increasing the oxidative stress status of the host. To determine if a lack of GPAT1 activity would influence the host response to infection, we infected GPAT1−/ − and wildtype mice with CVB3 and killed the mice ten days later. Heart pathology was significantly increased in GPAT1−/ − mice, although viral titers were not different. Measurement of mRNA levels in the hearts of infected mice for the proinflammatory immune mediators MCP-1, MIP-1α, TNF-α, and IL-2 revealed different patterns of expression between GPAT1−/ − and wildtype mice. Because infection with CVB3 induces inflammatory heart pathology, changes in membrane composition may affect immune function, resulting in alterations in heart pathology. Taken together, these data suggest that a lack of GPAT1 alters the immune response to a viral infection, perhaps by changing host redox status and/or immune cell membrane composition, thereby altering immune function.