In vivo treatment protocols. Stocks of wild-type Smith Strain MCMV salivary gland extracts [14] and bacterial artificial chromosome (BAC)-derived wild-type, DN-SCP-MCMV [44] , Dm157-MCMV, and m157-revertant were prepared as previously described [73] . Infections were initiated on day 0 with the i.p. delivery of 5 3 10 3 PFU (for in vivo-derived virus) or 2 3 10 5 PFU (for in vitro-derived virus). These modest doses were chosen because they do not induce lymphopenia in infected animals who harbor leukocyte numbers equal to or greater than those of uninfected controls (not shown). In addition, these doses are likely to be closer to the physiologic doses reached upon natural exposure to the virus through contact with infected animals. For the in vivo arrest of DN-SCP-MCMV replication, 200 lg of doxycycline was delivered by i.p. injection 20 h postinfection followed immediately by the addition of 2 mg/ml doxycycline plus 5% sucrose in the drinking water. 50,000 units of recombinant mouse IFN-a (HyCult Biotech, http://www.hbt.nl/) was administered by i.p. injection at 30 and 48 h post-MCMV infection. This dose was titrated in ELISA and shown to correspond to 25 ng of the ELISA IFN-a standard. Thus, since the cytokine titers measured by ELISA in the serum of BALB/c mice at 36 h post-infection range between 5 and 10 ng/ml, and the volume of the lymph and blood of an adult mouse can roughly be estimated around 5 ml, the dose of rmIFN-a injected in Klra8 mice should be similar to the physiologic levels of the cytokine naturally induced in infected BALB/c mice. NK cells were depleted by delivery of 100 lg of purified anti-NK1.1 mAb (PK136) on days À1 pre-MCMV infection, and days 1 and 3 post-MCMV infection. Control mice were treated with 100 lg of mouse IgG (Jackson ImmunoResearch Laboratories, http://www. jacksonimmuno.com/). Uninfected mice were depleted of NK cells on the schedule of day 4 infected mice. To assess NK cell depletion, a combination of anti-DX5 and anti-TCRb staining was used in order to avoid the risk of underevaluating the numbers of remaining NK cells, as may have occurred due to a potential problem of epitope masking if the antibody used for immunophenotyping had been the same as the one used for depletion. NK cell depletions were greater than 98% ( Figure S5) .