Identification of the myelin protein plasmolipin as the cell-entry receptor for Mus caroli endogenous retrovirus

Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, USA; Heinrich-Pette-Institut, Martinistrasse 52, D-20251 Hamburg, Germany

^* To whom correspondence should be addressed. Email: dmiller{at}fhcrc.org.

	Abstract

The Asian wild mouse species Mus caroli harbors an endogenous retrovirus (McERV) that is closely related to but distinct from the endogenous retrovirus family defined by Mus dunni endogenous virus (MDEV) and Mus musculus endogenous retrovirus (MmERV). McERV could infect some cell types from humans, dogs and rats, but not all, and did not infect any mouse cell line tested. Because of its interesting host range, its proposed ancestral relationship to primate retroviruses, and because none of the entry receptors for this family of retroviruses had been identified, we began a search for the McERV receptor. We determined the chromosomal location of the receptor gene in the human genome by phenotypic screening of the G3 human/hamster radiation hybrid cell line panel, and confirmed the localization by assaying for receptor activity conferred by BAC clones spanning the region. We next localized the gene more precisely in one positive BAC by assay for receptor activity following BAC digestion with several restriction enzymes that cleaved different sets of genes, and confirmed that the final candidate gene, plasmolipin (PLLP; TM4SF11), is the novel receptor by showing that expression of the human plasmolipin cDNA renders hamster and mouse cells susceptible to McERV infection. Plasmolipin functions as a voltage-dependent potassium ion channel and is primarily expressed in kidney and brain, helping explain the limited range of cell types that McERV can infect. Interestingly, mouse plasmolipin also functioned well as a receptor for McERV, but was simply not expressed in the mouse cell types we originally tested.