TWiV 1165: What Doesn't Kill Us Primes Our Macrophages - Summary
0:00 MicrobeTV Fundraiser: A call for listener support to sustain the production of high-quality science videos and podcasts.
7:30 Remembering Diane Griffin: The episode acknowledges the passing of prominent virologist Diane Griffin, highlighting her significant contributions to the field, particularly her work on measles and persistent viral RNA after infection.
11:19 First H5N1 in US Pigs: The USDA announces the first detection of H5N1 influenza in pigs on a backyard farm in Oregon, raising concerns about potential spillover from birds to mammals and reassortment possibilities. However, no mammalian adaptation markers were identified in the viral genome.
15:59 Snippet 1: Innate Immune Control of Influenza:
16:00: IFITM3, an interferon-induced membrane protein, is a potent antiviral factor that restricts infection by various enveloped viruses, including influenza.
18:14: A significant portion of the human population carries IFITM3 polymorphisms, potentially impacting susceptibility to viral infections.
21:00: Experiments in mice and human cells demonstrate that IFITM3 raises the minimum viral dose needed for successful infection, highlighting its role as a barrier to infection.
24:28: Serial passage of a human influenza virus in mice lacking IFITM3 resulted in viral adaptations that enhanced replication in wild-type mice, suggesting a role for IFITM3 in interspecies transmission.
29:29: Conversely, passage in mice lacking interferon signaling (STAT1 knockout) resulted in attenuated viruses, emphasizing the importance of interferon pressure in maintaining viral fitness.
33:01: The study concludes that IFITM3 is a crucial barrier to influenza virus emergence and adaptation.
36:49 Snippet 2: Trained Innate Immunity:
36:51: The paper explores "antiviral trained innate immunity," a phenomenon where prior exposure to a pathogen enhances the innate immune response to subsequent infections, even by unrelated pathogens.
38:41: This "memory" is attributed to epigenetic changes in immune cells, particularly alveolar macrophages (AMs), which reside in the lungs.
42:57: Mice infected with a mouse-adapted SARS-CoV-2 strain showed epigenetic modifications in their AMs 30 days post-infection, even after virus clearance.
46:27: Similar epigenetic changes were observed in AMs from human patients who had recovered from mild SARS-CoV-2 infections.
50:02: The study demonstrates that these epigenetic changes are primarily found in resident AMs, rather than monocyte-derived AMs that infiltrate the lungs during infection.
58:48: Functional assays revealed that AMs from SARS-CoV-2 recovered mice exhibit heightened responsiveness to immune stimuli and increased resistance to infection by VSV and influenza A virus.
1:01:54: Transfer of SARS-CoV-2 experienced AMs into naive mice conferred protection against influenza A virus challenge, demonstrating the protective role of trained AMs.
1:08:04: Prior SARS-CoV-2 infection protected mice from a lethal influenza A virus challenge, not by reducing viral replication, but by dampening the hyperinflammatory response typically associated with severe influenza.
1:18:53: The study concludes that this form of innate immune memory, shaped by prior pathogen exposure and the specific cell types involved, can significantly impact the outcome of subsequent infections.