Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (TH1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pTreg) conversion and promoting TH1 immunity to dietary antigen. Initiation of TH1 immunity to dietary antigen was dependent on interferon regulatory factor 1 and dissociated from suppression of pTreg conversion, which was mediated by type-1 interferon. Last, our study in humans supports a role for infection with reovirus, a seemingly innocuous virus, in triggering the development of CeD.

Mammalian orthoreoviruses (reoviruses) are highly useful models for studies of double-stranded RNA virus replication and pathogenesis. We previously developed a strategy to recover prototype reovirus strain T3D from cloned cDNAs transfected into murine L929 fibroblast cells. Here, we report the development of a second-generation reovirus reverse genetics system featuring several major improvements: (1) the capacity to rescue prototype reovirus strain T1L, (2) reduction of required plasmids from ten to four, and (3) isolation of recombinant viruses following transfection of baby hamster kidney cells engineered to express bacteriophage T7 RNA polymerase. The efficiency of virus rescue using the 4-plasmid strategy was substantially increased in comparison to the original 10-plasmid system. We observed full compatibility of T1L and T3D rescue vectors when intermixed to produce a panel of T1L × T3D monoreassortant viruses. Improvements to the reovirus reverse genetics system enhance its applicability for studies of reovirus biology and clinical use.

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Background Antibody response to the inactivated influenza vaccine is not well described in kidney transplant recipients on newer, but commonly used, immunosuppression medications. We hypothesized that kidney transplant recipient participants on tacrolimus-based regimens would have decreased antibody response compared with healthy controls. Study Design Prospective cohort study of 53 kidney transplant recipient and 106 healthy control participants over the 2006–2007 influenza season. All participants received standard inactivated influenza vaccine. Setting and participants Kidney transplant recipients on tacrolimus-based regimens at a single academic medical center and healthy controls. Predictor Presence of kidney transplant. Outcomes Proportion of participants achieving seroresponse (four-fold rise in antibody titer) and seroprotection (antibody titer greater than 1:32) one month after vaccination. Measurements Antibody titers before vaccination and one month after vaccination using hemagglutinin inhibition assays for influenza types A/H1N1, A/H3N2, and B. Results A smaller proportion of the transplantation group compared with the healthy control group developed the primary outcomes of seroresponse or seroprotection for all three influenza types at one month post vaccination. The response to influenza type A/H3N2 was statistically different, with the transplantation group having 69% decreased odds of developing seroresponse (95% CI 0.16 to 0.62, P = 0.001) and 78% decreased odds of developing seroprotection (95% CI 0.09 to 0.53, P = 0.001) compared with healthy controls. When participants less than 6 months from time of transplantation were considered, this group had significantly decreased response to the vaccine as compared with healthy controls. Limitations Decreased sample size; potential for confounders; outcome measure used is the standard but does not give information about vaccine efficacy. Conclusions Kidney transplant recipients, especially within 6 months of transplantation, had diminished antibody response to the 2006–07 inactivated influenza vaccine.

Deletion of the NS2 gene attenuates RSV in subjects of all ages studied. This validates the strategy of developing live respiratory tract virus vaccines in which the virus's ability to inhibit the human innate immune system is blocked. rA2cp248/404 Delta NS2 should be studied in children at a higher input titer, because it was more infectious and immunogenic than was rA2cp530/1009 Delta NS2.