IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity

Suthar, Mehul S.; Ma, Daphne Y.; Thomas, Sunil; Lund, Jennifer M.; Zhang, Nu; Daffis, Stephane; Rudensky, Alexander Y.; Bevan, Michael J.; Clark, Edward A.; Kaja, Murali-Krishna; Diamond, Michael S.; Gale, Michael

To define the role of IPS-1 in controlling WNV in vivo, wild type and IPS-1 2/2 mice were infected subcutaneously (s.c.) with 100 PFU of WN-TX and viral burden within peripheral tissues and the CNS was measured over time post-infection (pi). IPS-1 2/2 mice exhibited increased viremia compared to wild type mice (45.7 fold enhancement at day 1 pi, P,0.05) throughout the course of infection (Fig 1B) . Similarly, viral loads in the spleen were elevated in the infected IPS-1 2/2 mice (Fig 1C) . WNV infection of IPS-1 2/2 mice displayed an expanded tissue tropism as infectious virus was found in the kidneys, a tissue that is not normally permissive to infection in wild type mice ( Fig 1D) . WNV is typically detected in the CNS of wild type mice after s.c. challenge between 4 and 8 days pi [2] . Consistent with this time course, infected wild type mice exhibited detectable viral loads (average viral titer of 10 1.8 pfu/gram of tissue) in the brain by day 6 p.i., although virus was not detected in the spinal cord (Fig 1E and F ). In contrast, WNV spread to the brain ( Fig 1E) and spinal cord of IPS-1 2/2 mice (Fig 1F) by day 2 pi, with viral loads rising through day 6 pi. Together these results indicate that IPS-1, likely