Related Experiment Video
Updated: May 5, 2026
Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
Published on: December 21, 2019
Interfering residues narrow the spectrum of MLV restriction by human TRIM5alpha
Pierre V Maillard1, Séverine Reynard, Fatima Serhan
1Global Health Institute, School of Life Sciences, Frontiers in Genetics National Center for Competence in Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
Abstract:
TRIM5alpha is a restriction factor that limits infection of human cells by so-called N- but not B- or NB-tropic strains of murine leukemia virus (MLV). Here, we performed a mutation-based functional analysis of TRIM5alpha-mediated MLV restriction. Our results reveal that changes at tyrosine(336) of human TRIM5alpha, within the variable region 1 of its C-terminal PRYSPRY domain, can expand its activity to B-MLV and to the NB-tropic Moloney MLV. Conversely, we demonstrate that the escape of MLV from restriction by wild-type or mutant forms of huTRIM5alpha can be achieved through interdependent changes at positions 82, 109, 110, and 117 of the viral capsid. Together, our results support a model in which TRIM5alpha-mediated retroviral restriction results from the direct binding of the antiviral PRYSPRY domain to the viral capsid, and can be prevented by interferences exerted by critical residues on either one of these two partners.
Insights
Human TRIM5alpha restricts murine leukemia virus (MLV) infection. Mutations in TRIM5alpha or MLV capsid alter this restriction, revealing direct binding between TRIM5alpha and MLV capsid.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- TRIM5alpha acts as a cellular restriction factor, inhibiting retroviral infection.
- Specific strains of murine leukemia virus (MLV) are targeted by human TRIM5alpha.
Purpose of the Study:
- To investigate the molecular mechanisms underlying TRIM5alpha-mediated restriction of MLV.
- To identify key residues in TRIM5alpha and MLV capsid involved in this interaction.
Main Methods:
- Functional analysis using site-directed mutagenesis of human TRIM5alpha.
- Analysis of mutations in the MLV capsid protein.
- Assays to measure viral restriction and infectivity.
Main Results:
- Mutations at tyrosine(336) in the human TRIM5alpha PRYSPRY domain expanded its restriction activity to include B-MLV and Moloney MLV.
- Interdependent mutations in the MLV capsid (positions 82, 109, 110, 117) enabled viral escape from TRIM5alpha restriction.
- These findings support a direct binding model between the TRIM5alpha PRYSPRY domain and the MLV capsid.
Conclusions:
- TRIM5alpha restriction is mediated by direct interaction with the viral capsid.
- Specific residues on both TRIM5alpha and the viral capsid are critical for this interaction and can be modulated to alter restriction.
- Understanding these interactions provides insights into viral evasion strategies and potential therapeutic targets.
More Related Videos
Related Concept Videos
01:36Mismatch Repair
01:19Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...