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Updated: Aug 29, 2026
Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
Identification of an extracellular domain within the human PiT2 receptor that is required for amphotropic murine
Steven A Feldman1, Karen B Farrell, Ravi K Murthy
1Section on Molecular Virology, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Abstract:
Human PiT2 (PiT2) is a multiple-membrane-spanning protein that functions as a type III sodium phosphate cotransporter and as the receptor for amphotropic murine leukemia virus (A-MuLV). Human PiT1 (PiT1), another type III sodium phosphate cotransporter, is a highly related protein that functions as a receptor for gibbon ape leukemia virus but not for A-MuLV. The ability of PiT1 and PiT2 to function as discrete viral receptors with unique properties presumably is reflected in critical residue differences between these two proteins. Early efforts to map the region(s) within PiT2 that is important for virus binding and/or entry relied on infection results obtained with PiT1-PiT2 chimeric cDNAs expressed in Chinese hamster ovary (CHOK1) cells. These attempts to localize the PiT2 virus-binding site were hampered because they were based on infectivity, not binding, assays, and therefore, receptors that bound but failed to facilitate virus entry could not be distinguished from receptors that did not bind virus. Using a more accurate topological model for PiT2 as well as an A-MuLV receptor-binding assay, we have identified extracellular domain one (ECD1) of the human PiT2 receptor as being important for A-MuLV binding and infection.
Insights
Researchers identified the first extracellular domain (ECD1) of the human PiT2 protein as crucial for amphotropic murine leukemia virus (A-MuLV) binding and infection. This finding clarifies PiT2
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Human PiT2 (PiT2) is a type III sodium phosphate cotransporter and a receptor for amphotropic murine leukemia virus (A-MuLV).
- Human PiT1 (PiT1), a related protein, serves as a gibbon ape leukemia virus receptor but not for A-MuLV.
- Understanding PiT1 and PiT2 differences is key to their distinct viral receptor functions.
Purpose of the Study:
- To precisely map the regions of human PiT2 responsible for A-MuLV binding and viral entry.
- To overcome limitations of previous studies relying solely on infectivity assays.
Main Methods:
- Utilized an accurate topological model of the human PiT2 protein.
- Employed a specific amphotropic murine leukemia virus (A-MuLV) receptor-binding assay.
- Analyzed PiT1-PiT2 chimeric cDNAs expressed in Chinese hamster ovary (CHOK1) cells.
Main Results:
- Identified the first extracellular domain (ECD1) of human PiT2 as critical for A-MuLV binding.
- Demonstrated ECD1's importance for A-MuLV-mediated infection.
- Distinguished binding from entry functions, unlike previous infectivity-based studies.
Conclusions:
- The first extracellular domain (ECD1) of human PiT2 is essential for amphotropic murine leukemia virus (A-MuLV) binding and subsequent infection.
- This study refines the understanding of PiT2's role as a viral receptor.
- Provides a foundation for future studies on PiT2-viral interactions.
