TRIM21 is a molecular rheostat for influenza A virus replication
Teo, Q. W.; Lv, H.; Pholcharee, T.; Chen, X.; Ramadin, V.; Mao, K. J.; Huang, J. J.; Rivera-Cardona, J.; Zhu, J.; Huan, Y. W.; Shao, E. K.; Tun, H. M.; brooke, c.; Radoshevich, L.; Sanyal, S.; Wu, N. C.
Show abstract
TRIM21 is a multifunctional E3 ubiquitin ligase and intracellular antibody receptor, yet its role during viral infection remains unclear, with reports describing both antiviral and proviral activities. Here, we show that TRIM21 regulates influenza infection in an expression-dependent manner by functioning as a molecular rheostat rather than a binary restriction factor. This graded activity of TRIM21, which leads to both suppression and promotion of influenza replication, couples linkage-specific ubiquitination of viral nucleoprotein with modulation of innate immune signaling. Additionally, loss of TRIM21 unmasks a compensatory antiviral program centered on PRKDC, which is a ubiquitination target of TRIM21. This positions PRKDC as a latent restriction factor selectively engaged when primary TRIM21 control is lost. Together, these findings reveal a hierarchical and plastic antiviral network in which TRIM21 sets an adjustable threshold for host defense while restraining secondary restriction pathways. This framework highlights the sophisticated layers of regulation of the host ubiquitin-mediated antiviral immunity.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Human brain cell types shape host-rabies virus transcriptional interactions revealing a preexisting pro-viral astrocyte subpopulation 95%
- HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells 95%
- Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4+ T cells 95%
Similar papers in this journal
- A human-specific motif facilitates CARD8 inflammasome activation after HIV-1 infection 95%
- Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races 95%
- Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies 95%
Similar papers in this journal
Similar papers in this journal
- BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2 94%
- SETD2 maintains nuclear lamina stability to safeguard the genome 93%
- A quantitative ultrastructural timeline of nuclear autophagy reveals a role for dynamin-like protein 1 at the nuclear envelope 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.