Related Experiment Video

Updated: Jul 8, 2026

Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
10:40

Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods

Published on: December 21, 2019

Restraint of Powassan virus replication by TRIM5α facilitates viral avoidance of antiviral immunity

Rebecca M Broeckel1,2, Emily A Fitzmeyer1,3, Eva Chebishev1

  • 1Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

Communications Biology
|July 6, 2026
PubMed

Insights

Primate TRIM5α restricts tick-borne orthoflaviviruses, acting as a cellular barrier. A mutation in Powassan virus allowed escape from TRIM5α inhibition, impacting early immune responses.

Area of Science:

  • Virology
  • Immunology
  • Genetics

Background:

  • TRIpartite Motif protein 5 alpha (TRIM5α) inhibits lentivirus replication.
  • Previous studies showed primate TRIM5α restricts some orthoflaviviruses but not Powassan virus (POWV).

Purpose of the Study:

  • To characterize the interaction between primate TRIM5α and orthoflaviviruses.
  • To investigate why POWV evades TRIM5α restriction.

Main Methods:

  • Screened TRIM5α variants from various primates for restriction capacity against orthoflaviviruses.
  • Introduced a specific mutation into a POWV molecular clone to assess its effect on TRIM5α inhibition.
  • Infected human dendritic cells with wild-type and mutant POWV.

Main Results:

  • TRIM5α from African green monkey, De Brazza's monkey, and chimpanzee restricted tick-borne orthoflaviviruses.
  • A POWV NS3 mutation conferred resistance to all tested primate TRIM5α proteins.
  • TRIM5α-resistant POWV showed high early replication and induced strong interferon responses in human dendritic cells.

Conclusions:

  • Primate TRIM5α acts as a cellular barrier against tick-borne orthoflaviviruses.
  • TRIM5α restriction limits viral replication, potentially preventing early innate immune detection.
  • POWV's ability to escape TRIM5α restriction influences its replication and host immune response.

More Related Videos

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors06:02

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors

Published on: September 13, 2018

Related Concept Videos

Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
The Antiviral System of Bacteria and Archaea: CRISPR01:23

The Antiviral System of Bacteria and Archaea: CRISPR

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this defense.
Antiviral Nucleoside Inhibitors01:22

Antiviral Nucleoside Inhibitors

Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...