Related Experiment Video
Updated: Aug 19, 2026

Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells
Published on: November 12, 2015
An endoplasmic reticulum retrieval signal partitions human foamy virus maturation to intracytoplasmic membranes
1Departments of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-2170, USA. paulg@uab.edu
Abstract:
Among all retroviruses, foamy viruses (FVs) are unique in that they regularly mature at intracytoplasmic membranes. The envelope glycoprotein of FV encodes an endoplasmic reticulum (ER) retrieval signal, the dilysine motif (KKXX), that functions to localize the human FV (HFV) glycoprotein to the ER. This study analyzed the function of the dilysine motif in the context of infectious molecular clones of HFV that encoded mutations in the dilysine motif. Electron microscopy (EM) demonstrated virion budding both intracytoplasmically and at the plasma membrane for the wild-type and mutant viruses. Additionally, mutant viruses retained their infectivity, but viruses lacking the dilysine signal budded at the plasma membrane to a greater extent than did wild-type viruses. Interestingly, this relative increase in budding across the plasma membrane did not increase the overall release of viral particles into cell culture media as measured by protein levels in viral pellets or infectious virus titers. We conclude that the dilysine motif of HFV imposes a partial restriction on the site of viral maturation but is not necessary for viral infectivity.
Insights
Human foamy virus (HFV) uses a dilysine motif to control where viral particles mature. This motif restricts budding to intracellular membranes but is not essential for infectivity.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Foamy viruses (FVs) are unique retroviruses that mature at intracytoplasmic membranes.
- The human foamy virus (HFV) envelope glycoprotein contains a dilysine (KKXX) motif, directing it to the endoplasmic reticulum (ER).
Purpose of the Study:
- To investigate the function of the dilysine motif in HFV maturation and infectivity.
- To determine the role of the ER retrieval signal in viral particle release and localization.
Main Methods:
- Construction of infectious molecular clones of HFV with mutations in the dilysine motif.
- Analysis of virion budding sites using electron microscopy (EM).
- Quantification of viral particle release and infectivity titers.
Main Results:
- Mutant HFV viruses exhibited both intracytoplasmic and plasma membrane budding, similar to wild-type.
- Viruses lacking the dilysine signal showed increased budding at the plasma membrane.
- Despite altered budding sites, mutant viruses retained infectivity and overall viral release levels were unchanged.
Conclusions:
- The dilysine motif partially restricts the site of HFV maturation to intracellular membranes.
- This motif is not essential for HFV infectivity, but influences the localization of viral budding.
Related Concept Videos
Intralumenal Vesicles and Multivesicular Bodies
Vesicular Tubular Clusters
With the help of motor proteins such...
ER Retrieval Pathway
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The Endoplasmic Reticulum
Directing Proteins to the Rough Endoplasmic Reticulum
Insertion of Single-pass Transmembrane Proteins in the RER
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...

