Welcome to the IUMS 2022 Interactive Program

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Beyond retroviruses: restriction of flavivirus replication by TRIM5α

TRIpartite Motif (TRIM) proteins belong to a large protein family, many of which are inducible by type I interferon and serve to suppress virus infection through direct interactions with viral proteins. Primate TRIM5α is a consequential inhibitor that suppresses lentivirus replication (e.g HIV-1) in a highly host species- and virus species-specific fashion to limit cross-species transmission of these viruses. Importantly, the antiviral effects of TRIM5α have been thought to function exclusively in the context of lentivirus infection. Our research interests center on the flaviviruses that include significant pathogens that have emerged into human populations from primates (e.g. dengue virus, Zika virus, yellow fever virus) prompting us to determine whether TRIM5α could also function to inhibit flavivirus replication. Surprisingly, this work has revealed a new function for TRIM5α as a potent restriction factor for replication of specific flaviviruses. The mechanisms of restriction, flavivirus escape, and the implications of TRIM5α as an early barrier to flavivirus replication will be discussed.

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Trained immunity: a memory for innate host defense

Mihai G. Netea, Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands

The inability of innate immunity to build an immunological memory, considered one of the main characteristics differentiating it from adaptive immunity, has been recently challenged by studies in plants, invertebrates, and mammals. Long-term reprogramming of innate immunity, that induces adaptive traits and has been termed trained immunitycharacterizes prototypical innate immune cells such as natural killer cells and monocytes, and provides protection against reinfection in a T/B-cell-independent manner. In contrast, trained immunity has been shown to be able to induce protection against reinfection in a lymphocyte-independent manner. Non-specific protective effects dependent on trained immunity have also been shown to be induced after BCG vaccination in humans. Specific signaling mechanisms including the dectin-1/Raf1 and NOD2-mediated pathways induce trained immunity, through induction of histone modifications (methylation, acetylation) and epigenetic reprogramming of monocyte function. Complex immunological and metabolic circuits link cell stimulation to a long-term epigenetic reprogramming of its function. The concept of trained immunityrepresents a paradigm change in immunity and its putative role in infection and inflammation may represent the next step in the design of future vaccines and immunotherapeutic approaches.