Mechanisms of cardiovascular defects due to endotheliotropic virus infection

In this article, the literature on some endotheliotropic viruses such as parvovirus B19 (PVB19) and human herpesvirus-6 (HHV-6) was reviewed to update the current information on the pathogenesis of cardiovascular dysfunction. PVB19 targets exclusively endothelial cells in microvasculature by binding to P antigen receptors and co-receptors such as α5 β1 integrin and Ku80 autoantigen, whereas HHV-6 targets all cardiovascular cells by utilising CD46 and CD134 to infect predominantly cardiomyocytes. The activation of endothelial cell by PVB19 produces upregulation of some adhesion molecules, cytokine release and recruitment of inflammatory cells in acute phase. In chronic phase, there occurs pro-inflammatory environment in microvasculature which is associated with reduced production of nitric oxide (NO), impaired vasodilatory capacity, occurrence of ischaemia in cardiomyocytes and development of cardiomyopathy. On the other hand, HHV-6 infection not only induces cardiac defects due to ischaemic insult by endothelial/microvasculature dysfunction like PVB19, but also produces myocardial abnormalities by directly affecting cardiomyocytes by inducing chromosomal integration as well as promoting infiltration of immune cells and pro-inflammatory cells. Such alterations in cardiomyocytes by HHV-6 virus as a consequence of ischaemic conditions, mitochondrial dysfunction, Ca2+-handling abnormalities, inflammatory environment and immune processes are considered to explain the occurrence of cardiac apoptosis as well as cardiac fibrosis, structural damage and cardiac dysfunction. In view of these observations indicating similarities and differences in the mode of cardiovascular defects induction by PVB19 and HHV-6 infections, extensive research needs to be carried out for fully understanding the exact mechanisms of viral cardiomyopathy.