A new member of the Orthomyxoviridae family, influenza D virus (IDV), was first reported in swine in the Midwest region of the United States. This study aims to extend our knowledge on the IDV epidemiology and to determine the impact of bovine production systems on virus spread. A total of 15 isolates were recovered from surveillance of bovine herds in Mississippi, and two genetic clades of viruses co-circulated in the same herd. Serologic assessment from neonatal beef cattle showed 94% seropositive, and presumed maternal antibody levels were substantially lower in animals over six months of age. Active IDV transmission was shown to occur at locations where young, weaned, and comingled calves were maintained. Serological characterization of archived sera suggested that IDV has been circulating in the Mississippi cattle populations since at least 2004. Continuous surveillance is needed to monitor the evolution and epidemiology of IDV in the bovine population.

In this issue of Molecular Cell, an activator of the PIDDosome (a complex comprising of PIDD, RAIDD, and caspase-2) is described in experiments detailing endogenous PIDDosome assembly and caspase-2 function after DNA damage in the presence of Chk1 suppression (Ando et al., 2012).

for your guidance as I pursued my doctoral degree. I sincerely appreciate the time which you invested in my education and the opportunity to learn from scientists whom I regard with so much respect. Last, I thank my mentor Dr. Richard Webby for the opportunity to work in your lab and for your mentorship. I learned not only how to think scientifically but how to act as a leader. I have no doubt that the lessons learned in my doctoral education will benefit me for the rest of my career.

Since its detection in swine, Influenza D virus (IDV) has been shown to be present in multiple animal hosts, and bovines have been identified as its natural reservoir. However, it remains unclear how IDVs emerge, evolve, spread, and maintain in bovine populations. Through multiple years of virological and serological surveillance in a single order-buyer cattle facility in Mississippi, we showed consistently high seroprevalence of IDVs in cattle, and recovered a total of 32 IDV isolates from both healthy and sick animals including those with antibodies against IDV. Genomic analyses of these isolates along with those isolated from other areas showed that active genetic reassortment occurred in IDV and that five reassortants were identified in the Mississippian facility. Two antigenic groups were identified through antigenic cartography analyses for these 32 isolates and representative IDVs from other areas. Remarkably, existing antibodies could not protect cattle from experimental reinfection with IDV. Additional phenotypic analyses demonstrated variations in growth dynamics and pathogenesis in mice between viruses independent of genomic constellation. In summary, this study suggests that, in addition to epidemiological factors, the ineffectiveness of pre-existing immunity and cocirculation of a diverse viral genetic pool could facilitate its high prevalence in animal populations. IMPORTANCE Influenza D viruses (IDVs) are panzootic in multiple animal hosts, but the underlying mechanism is unclear. Through multiple years of surveillance in the same order-buyer cattle facility, 32 IDV isolates were recovered from both healthy and sick animals including those with evident antibodies against IDV. Active reassortment occurred in the cattle within this facility and in those across other areas, and multiple reassortants co-circulated in animals. These isolates are shown with a large extent of phenotypic diversity in replication efficiency and pathogenesis but little in antigenic properties. Animal experiment demonstrated that existing antibodies could not protect cattle from experimental reinfection with IDV. This study suggests that, in addition to epidemiological factors, limited protection from pre-existing immunity against IDVs in cattle herds and cocirculation of a diverse viral genetic pool likely facilitate the high prevalence of IDVs in animal populations.

Background:In the basal state, oocytes produce lactate from G6P even in the presence of oxygen. Results: Addition of G6P to egg extracts inhibits PP1, preventing dephosphorylation/inactivation of CaMKII and initiation of apoptotic pathways. Conclusion: Normal oocyte metabolism suppresses apoptosis by inhibiting PP1 and activating CaMKII. Significance: These mechanistic insights suggest potential targets for modulating cell death.

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