The selective targeting of HLA-C and -G by US10 in the context of congenital HCMV infections could have significant implications at the maternal-fetal interface. HLA-C and -G are crucial in regulating interactions between maternal immune cells and fetal cells, particularly in the placenta. HLA-C is known to interact with killer cell immunoglobulin-like receptors (KIRs) on maternal NK cells, influencing their activity and preventing NK cell-mediated attack on the fetus. HLA-G, on the other hand, plays a key role in immune tolerance at the maternal-fetal interface by inhibiting maternal immune responses against the semi-allogeneic fetus.
By targeting HLA-C and -G, US10 may disrupt the delicate balance of immune tolerance and immune activation at the maternal-fetal interface. This could potentially lead to increased immune recognition of fetal cells by maternal immune cells, triggering inflammatory responses that could be detrimental to the developing fetus. Additionally, dysregulation of HLA-C and -G expression by US10 may impact the balance of immune checkpoints and regulatory mechanisms that are crucial for maintaining a healthy pregnancy.