Related Experiment Videos
A family of retroviruses that utilize related phosphate transporters for cell entry
1Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Abstract:
The amphotropic murine retrovirus receptor Ram-1 shows significant sequence similarity to the gibbon ape leukemia virus (GALV) receptor Glvr-1, and both of these cell surface virus receptors normally function as sodium-dependent phosphate symporters. However, Ram-1 from humans or rats does not serve as a receptor for GALV, and Glvr-1 from humans does not serve as a receptor for amphotropic virus. Here we show that the murine retrovirus 10A1 can enter cells by using either Glvr-1 or Ram-1. Furthermore, we have constructed Ram-1/Glvr-1 hybrid receptors that allow entry of both GALV and amphotropic virus. While GALV and amphotropic virus are in separate interference groups when assayed on human cells, they do interfere with each other in cells expressing the hybrid receptor. These results indicate a close functional relationship between retroviruses that utilize members of this newly defined receptor family and provide a molecular explanation for nonreciprocal and cell type-specific interference observed for some retrovirus classes.
Insights
Murine retrovirus receptors Ram-1 and Glvr-1 function as phosphate symporters. Hybrid receptors enabled entry for both gibbon ape leukemia virus (GALV) and amphotropic virus, revealing a close functional relationship.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- The amphotropic murine retrovirus receptor Ram-1 and gibbon ape leukemia virus (GALV) receptor Glvr-1 are sequence-similar cell surface proteins.
- Both Ram-1 and Glvr-1 function as sodium-dependent phosphate symporters.
- Species-specific differences exist in receptor usage; human/rat Ram-1 does not bind GALV, and human Glvr-1 does not bind amphotropic virus.
Purpose of the Study:
- To investigate the receptor usage of murine retrovirus 10A1.
- To explore the functional capacity of Ram-1/Glvr-1 hybrid receptors.
- To elucidate the relationship between retroviruses utilizing the Ram-1/Glvr-1 receptor family.
Main Methods:
- Utilized retroviral entry assays with different cell lines expressing Ram-1, Glvr-1, or hybrid receptors.
- Constructed and tested Ram-1/Glvr-1 hybrid receptors.
- Performed interference assays to assess viral tropism and receptor interactions.
Main Results:
- Murine retrovirus 10A1 can utilize either Glvr-1 or Ram-1 for cell entry.
- Ram-1/Glvr-1 hybrid receptors facilitated entry of both GALV and amphotropic virus.
- GALV and amphotropic virus, typically in separate interference groups on human cells, interfered with each other on cells expressing hybrid receptors.
Conclusions:
- Retroviruses using Ram-1 and Glvr-1 receptors share a close functional relationship.
- Hybrid receptors provide a molecular basis for understanding nonreciprocal and cell-type-specific retroviral interference patterns.
- This study defines a new family of retroviral receptors with implications for viral tropism and host range.