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engineered prototype foamy virus Env receptor-binding domain variants

Candidate: toolkit itemType: construct pattern1 source documents6 linked claims
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Aliases

PFV Env RBD variants, targeted residue substitutions and combinatorial mutations spanning the upper domain and lower domain

Extracted Explainers

What the tool is doing

This engineered construct class modifies the PFV Env receptor-binding domain through targeted and combinatorial residue substitutions to alter HS-dependent entry and transduction. The paper reports both loss-of-function and gain-of-function variants.

Source 1DOIPubMed

Resources required

The abstract supports the need for in silico structural modeling, molecular docking, systematic mutagenesis, and quantitative cell-based transduction assays. Functional validation also used an inducible stable producer-cell platform.

Source 1DOIPubMed

What problem it solves

It addresses the previously undefined structural basis of PFV Env interaction with heparan sulfate while seeking to improve viral entry and gene transfer efficiency.

Source 1DOIPubMed

What it does not solve

The abstract does not show that these variants solve all PFV delivery limitations beyond entry efficiency. Some engineered changes abolished infectivity or failed when domains were replaced across species.

Source 1DOIPubMed

Alternatives

The source contrasts targeted PFV residue substitutions and combinatorial PFV variants with interspecies domain replacement using simian foamy virus Env, which reduced infectivity.

Source 1DOIPubMed

Evidence Snippets

We applied a structure-guided engineering strategy combining in silico structural modeling, molecular docking, and systematic mutagenesis of the PFV Env receptor-binding domain (RBD), targeted residue substitutions, and combinatorial mutations spanning the upper domain (UD) and lower domain (LD) were generated and evaluated using quantitative cell-based transduction assays.
Evidence 1Source 1DOIPubMedprovenance

Supporting Sources

Linked Claims

Claim 1engineering conclusionsupports2026Source 1DOIPubMed

Residue-level structure-guided engineering can enhance PFV transduction efficiency and helps define structural determinants of heparan sulfate recognition.

Quoted textsource-backed
These findings define the structural determinants of HS recognition in PFV Env and demonstrate that residue-level, structure-guided engineering can enhance PFV transduction efficiency.
Claim 2mechanism structure functionsupports2026Source 1DOIPubMed

Specific upper-domain PFV Env residues R298, R440, and E446 are essential for heparan sulfate-mediated attachment because alanine substitution abolishes infectivity.

Quoted textsource-backed
Alanine substitutions at R298, R440, and E446 in the UD abolished infectivity, confirming their essential roles in HS-mediated attachment.
Claim 3negative comparisonsupports2026Source 1DOIPubMed

Interspecies domain replacement with simian foamy virus Env reduces infectivity, indicating that PFV-heparan sulfate interactions are context specific.

Quoted textsource-backed
Interspecies domain replacement with simian foamy virus Env reduced infectivity, underscoring the context-specific nature of PFV-HS interactions.
Claim 4performance improvementsupports2026Source 1DOIPubMed

Selective PFV Env substitutions Q296R, G403F, E232N, I330F, and I334F enhance transduction efficiency relative to wild type by up to 1.32-fold.

Quoted textsource-backed
selective substitutions at adjacent positions, Q296R and G403F in the UD, and E232N, I330F, and I334F in the LD, enhanced transduction efficiency by up to 1.32-fold relative to the wild type
Claim 5synergysupports2026Source 1DOIPubMed

Combinatorial PFV Env variants integrating beneficial upper-domain and lower-domain mutations show synergistic improvement in transduction efficiency over wild type.

Quoted textsource-backed
Combinatorial variants integrating beneficial UD and LD mutations exhibited synergistic effects, achieving a transduction efficiency of 68.9%, corresponding to a 1.55-fold increase over the wild type (44.4%).
Claim 6validation platform resultsupports2026Source 1DOIPubMed

In the Tet-On-inducible stable producer cell system, the LD var6 mutant outperformed wild type in transduction, reaching 8.6% versus 4.4%, up to 1.95-fold higher.

Quoted textsource-backed
In the inducible stable cell system, the LD var6 mutant achieved 8.6% transduction compared to 4.4% for the wild type, representing up to a 1.95-fold increase.