A Putative Thiamine Transport Protein Is a Receptor for Feline Leukemia Virus Subgroup A

Abstract

Feline leukemia virus (FeLV) is a horizontally transmitted virus that causes a variety of proliferative and immunosuppressive diseases in cats. There are four subgroups of FeLV, A, B, C, and T, each of which has a distinct receptor requirement. The receptors for all but the FeLV-A subgroup have been defined previously. Here, we report the identification of the cellular receptor for FeLV-A, which is the most transmissible form of FeLV. The receptor cDNA was isolated using a gene transfer approach, which involved introducing sequences from a feline cell line permissive to FeLV-A into a murine cell line that was not permissive. The feline cDNA identified by this method was approximately 3.5 kb, and included an open reading frame predicted to encode a protein of 490 amino acids. This feline cDNA conferred susceptibility to FeLV-A when reintroduced into nonpermissive cells, but it did not render these cells permissive to any other FeLV subgroup. Moreover, these cells specifically bound FeLV-A-pseudotyped virus particles, indicating that the cDNA encodes a binding receptor for FeLV-A. The feline cDNA shares ϳ93% amino acid sequence identity with the human thiamine transport protein 1 (THTR1). The human THTR1 receptor was also functional as a receptor for FeLV-A, albeit with reduced efficiency compared to the feline orthologue. On the basis of these data, which strongly suggest the feline protein is the orthologue of human THTR1, we have named the feline receptor feTHTR1. Identification of this receptor will allow more detailed studies of the early events in FeLV transmission and may provide insights into FeLV pathogenesis.

Identification of a Novel Subgroup of Koala Retrovirus from Koalas in Japanese Zoos

“…We found that lacZ(KoRV-J) interfered with FeLV-A on FEA cells (feline fibroblasts). The receptor for FeLV-A is known to be THTR1 (29,30). As shown in Fig.…”

Identification of a retroviral receptor used by an Envelope protein derived by peptide library screening

“…The identification of the A5 receptor was facilitated by a preexisting cDNA library from feline AH927 cells within the pMX1 retroviral vector (9). The general scheme of the cDNA screening is outlined in Fig.…”

“…The feline AH927 cDNA library expressed within the retroviral pMX1 backbone was a gift of Julie Overbaugh (Fred Hutchinson Cancer Research Center, Seattle, WA) (9). One hundred nanograms of the AH927 cDNA library was introduced into Ultramax DH5␣ FT chemically competent cells (Gibco-BRL Life Technologies, Gaithersburg, MD) and plated onto six (245 ϫ 245-mm) plates containing LB carbenicillin (100 mg/ml), yielding 1.22 ϫ 10 7 colonies.…”

“…A correlation between the type of membrane protein serving as the receptor and the retroviral genus can be observed. All known ␥-retroviral receptors are multitransmembrane channels or transporters, including the MuLV ecotropic M-MuLV [MCAT (1)] and M813 [SMIT1 (2)]; the amphotropic [PiT-1/2 (3-5)], xenotropic, and polytropic receptors [Xpr1 (6)(7)(8)]; as well as the FeLV A [THTR1 (9)], B [PiT1 (10)], and C [FLVCR (11)(12)(13)] viral receptors. With these evolutionary observations, it is of great interest as to whether a given retrovirus must remain restricted to use receptors within the broad class of the original receptor or can be altered to use receptors beyond these protein family boundaries.…”

Vírus da leucemia felina: análise da classificação da infecção, das técnicas de diagnóstico e da eficácia da vacinação com o emprego de técnicas sensíveis de detecção viral

“…A proteína de membrana hospedeira utilizada como receptor é a Feline highaffinity thiamine transporter 1 (feTHTR1),encontrada em tecidos de absorção como intestino delgado, fígado e rins, e também em células do sistema linfóide (MENDOZA et al, 2006). Essa ampla distribuição é consistente com o fato de que o FeLV-A é encontrado nesses diversos tecidos e células (HOOVER et al, 1977) e pode explicar a vantagem sobre os outros subgrupos no que diz respeito à transmissibilidade.…”