Regulatory T (T reg ) cells have recently been shown to contribute to the dampening of inflammation and adaptive immune responses during acute virus infections [26, 43, 44] . Moreover, a reduction in the number of circulating T reg in mice leads to enhanced lethality after WNV infection [45] . A time course analysis of T regs in wild type mice revealed that WNV infection results in a significant increase in the numbers of FoxP3+ T cells as compared to mock-infected mice beginning on day 4 and peaking by day 6 pi (Fig 7C) , indicating the expansion of T regs during acute WNV infection. Despite their marked increase in viral load, the infected IPS-1 2/2 mice did not display an increase in the numbers of FoxP3+ T cells at any timepoint analyzed. Thus, IPS-1 signaling directly or indirectly impacts T reg proliferation and does so independently of viral load.