HHV-6 can directly infect vascular and lymphatic endothelial cells (ECs), and through expression of the viral gene U94/rep causes the inhibition of angiogenesis in blood and lymphatic ECs (Caruso 2009). The finding that HHV-6 induces the inhibition of angiogenesis—a vital process that contributes to essential bodily functions such as blood vessel growth/development and wound healing, but also serves as a fundamental step in the development of malignant tumors—has lead researchers to believe that understanding the antiangiogenic properties of U94/rep may lead to the potential control of blood and lymphatic EC proliferation.

The ability of HHV-6 to directly infect endothelial cells has many clinical implications. In one study, viral persistence in the myocardium (including many cases of HHV-6 myocarditis) was found to significantly correlate with endothelial dysfunction (Vallbracht 2004). The same group also found that in patients with nonischemic cardiomyopathy (12/71 cases positive for HHV-6), individuals with viral persistence experienced endothelial dysfunction of the coronary microciruculation, a risk factor that negatively affects prognosis (Vallbracht 2005). Additional studies have shown that HHV-6 can directly cause vascular endothelial injury, which may be a significant cause of thrombotic microangiopathy, a serious complication of bone marrow transplant (Takatsuka 2003, Matsuda 1999).

For more information on the consequences of endothelial cell dysfunction caused by HHV-6, visit our pages on HHV-6 & Heart Disease and HHV-6 & Mononucleosis/Lymphadenopathy.

Key Papers: HHV-6 & Endothelial Cell Dysfunction/Arteriopaties

Broccolo 2013 Possible role of HHV-6 as a trigger of autoimmune disease
Magnoni 2012 Molecular study of HHV-6 and HHV-8 involvement of coronary atherosclerosis and coronary instability
Caruso 2009 U94 of human herpesvirus 6 inhibits in vitro angiogenesis and lymphangiogenesis.
Vallbracht 2005 Differential aspects of endothelial function of the coronary microcirculation considering myocardial virus persistence, endothelial activation, and myocardial leukocyte infiltrates
Vallbracht 2004 Endothelium-dependent flow-mediated vasodilation of systemic arteries is impairted in patients with myocardial virus persistence
Takatsuka 2003 Endothelial damage caused by cytomegalovirus and human herpesvirus-6.
Matsuda 1999 Thrombotic microangiopathy associated with reactivation of human herpesvirus-6 following high-dose chemotherapy with autologous bone marrow transplantation in young children.