Researchers at the University of Ferrara, Italy, have published a new article in the Archives of Virology detailing HLA molecule modulation caused by HHV-6A infection of mesothelial cells. Their study demonstrates, for the first time, that human mesothelial cells are susceptible to HHV-6A infection in vitro. They also show that the virus causes modulated HLA expression on the cell surface, inducing the de novo expression of HLA class II and HLA-G.
Human mesothelial cells do not normally express HLA class II antigens at baseline, so the induction of HLA II expression by HHV-6A infection may lead to changes in the behavior of antigen presenting cells or the process of surface-level viral antigen recognition and, thus, immune cell activation. Furthermore, the article demonstrates that HHV-6A+ mesothelial cells can go on to induce T cell activation. In fact, the group observed a five-fold increase in T cell proliferation in the presence of HHV-6A+ mesothelial cells than controls.
However, after 72 hours, infected mesothelial cells were no longer able to induce T cell proliferation. The authors suggest that the increased expression of HLA-G observed at this time point may indicate that this element is acting as an inhibitory molecule, capable of changing the antigen presentation ability of mesothelial cells. Indeed, addition of anti-HLA-G antibody to the culture was able to restore T cell proliferation. The authors suggest that this virus-induced perturbation might be correlated to alterations in mesothelium functions, that include synthesis of pro-inflammatory cytokines, growth factors and extracellular matrix proteins and the secretion of glycosaminoglycans and lubricants, that may protect the body against infection and tumor dissemination.
This study adds mesothelial cells to the growing list of cellular tropism for HHV-6A, which has been previously shown to infect lymphocytes, astrocytes, oligodendrocytes, thyrocytes, vascular endothelial cells, and lymphatic endothelial cells. While HHV-6A infection has been shown to upregulate class II HLA on dendritic cells and epithelial thyroid cells, some have reported class I HLA upregulation as well, particularly in dendritic cells (Gustafsson 2013, Gustafsson 2015). HLA modulation due to infection by HHV-6A and HHV-6B has become an area of increased focus as researchers seek to understand the immunological ramifications of these viruses (Iampietro 2014).
For more information, read the full paper.