Publications by authors named "R E Donohue"

It is increasingly appreciated that pathogens can spread as infectious units constituted by multiple, genetically diverse genomes, also called collective infectious units or genome collectives. However, genetic characterization of the spatial dynamics of collective infectious units in animal hosts is demanding, and it is rarely feasible in humans. Measles virus (MeV), whose spread in lymphatic tissues and airway epithelia relies on collective infectious units, can, in rare cases, cause subacute sclerosing panencephalitis (SSPE), a lethal human brain disease.

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The control of the initial outbreak and spread of SARS-CoV-2/COVID-19 via the application of population-wide non-pharmaceutical mitigation measures have led to remarkable successes in dampening the pandemic globally. However, with countries beginning to ease or lift these measures fully to restart activities, concern is growing regarding the impacts that such reopening of societies could have on the subsequent transmission of the virus. While mathematical models of COVID-19 transmission have played important roles in evaluating the impacts of these measures for curbing virus transmission, a key need is for models that are able to effectively capture the effects of the spatial and social heterogeneities that drive the epidemic dynamics observed at the local community level.

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Measles virus (MeV), like all viruses of the order , utilizes a complex consisting of genomic RNA, nucleoprotein, the RNA-dependent RNA polymerase, and a polymerase cofactor, the phosphoprotein (P), for transcription and replication. We previously showed that a recombinant MeV that does not express another viral protein, C, has severe transcription and replication deficiencies, including a steeper transcription gradient than the parental virus and generation of defective interfering RNA. This virus is attenuated and However, how the C protein operates and whether it is a component of the replication complex remained unclear.

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Here, we show that cells expressing the adherens junction protein nectin-1 capture nectin-4-containing membranes from the surface of adjacent cells in a -endocytosis process. We find that internalized nectin-1-nectin-4 complexes follow the endocytic pathway. The nectin-1 cytoplasmic tail controls transfer: its deletion prevents -endocytosis, while its exchange with the nectin-4 tail reverses transfer direction.

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Background: Licensed vaccines are urgently needed for emerging infectious diseases, but the nature of these epidemics causes challenges for the design of phase III trials to evaluate vaccine efficacy. Designing and executing rigorous, fast, and ethical, vaccine efficacy trials is difficult, and the decisions and limitations in the design of these trials encompass epidemiological, logistical, regulatory, statistical, and ethical dimensions.

Results: Trial design decisions are complex and interrelated, but current guidance documents do not lend themselves to efficient decision-making.

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