NEMO deficiency - Patients can develop invasive HSV infections. This susceptibility likely reflects decreased NK cell function in these patients. Invasive gram positive and gram negative bacterial infections as well as mycobacterial infections also occur.
Wiskott-aldrich syndrome - This disease is characterized by recurrent HSV infections in 12% of patients.
Complete STAT 1 deficiency - Homozygous STAT1 deficiency is associated with fatal HSV infections as well as mycobacterial infections in infancy (due to impaired IFN-alpha/beta and IFN-gamma signaling respectively).
TLR3 deficiency - This disease has been reported in two patients with HSV encephalitis. TLR3 is important for the induction of IFN alpha/beta and innate viral defense. These patients did not develop other serious infections. A TLR3 mutation has also been reported in 1 of 3 patients with influenza-associated encephalopathy.
UNC 93B Deficiency case was reported in 2 of 86 patients with HSV encephalitis. These patients did not produce IFN alpha/beta in response to TLR 7, 8, or 9 stimulation. Patients did not develop other serious infections.
Caspase 8 deficiency (aka ALPS IIb) - Recurrent HSV infections have been reported in 2 patients. These patients presented with lymphadenopathy, splenomegaly, defective apoptosis, and immunodeficiency.