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Sodium-dependent neutral amino acid transporter type 1 is an auxiliary receptor for baboon endogenous retrovirus.

ABSTRACT: The baboon endogenous retrovirus (BaEV) belongs to a large, widely dispersed interference group that includes the RD114 feline endogenous virus and primate type D retroviruses. Recently, we and another laboratory independently cloned a human receptor for these viruses and identified it as the human sodium-dependent neutral amino acid transporter type 2 (hASCT2). Interestingly, mouse and rat cells are efficiently infected by BaEV but only become susceptible to RD114 and type D retroviruses if the cells are pretreated with tunicamycin, an inhibitor of protein N-linked glycosylation. To investigate this host range difference, we cloned and analyzed NIH Swiss mouse ASCT2 (mASCT2). Surprisingly, mASCT2 did not mediate BaEV infection, which implied that mouse cells might have an alternative receptor for this virus. In addition, elimination of the two N-linked oligosaccharides from mASCT2 by mutagenesis, as substantiated by protein N-glycosidase F digestions and Western immunoblotting, did not enable it to function as a receptor for RD114 or type D retroviruses. Based on these results, we found that the related ASCT1 transporters of humans and mice are efficient receptors for BaEV but are relatively inactive for RD114 and type D retroviruses. Furthermore, elimination of the two N-linked oligosaccharides from extracellular loop 2 of mASCT1 by mutagenesis enabled it to function as an efficient receptor for RD114 and type D retroviruses. Thus, we infer that the tunicamycin-dependent infection of mouse cells by RD114 and type D retroviruses is caused by deglycosylation of mASCT1, which unmasks previously buried sites for viral interactions. In contrast, BaEV efficiently employs the glycosylated forms of mASCT1 that occur normally in untreated mouse cells.

SUBMITTER: Marin M

PROVIDER: S-EPMC112341 | biostudies-literature | 2000 Sep

REPOSITORIES: biostudies-literature

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Sodium-dependent neutral amino acid transporter type 1 is an auxiliary receptor for baboon endogenous retrovirus.

Marin M M Tailor C S CS Nouri A A Kabat D D

Journal of virology 20000901 17

The baboon endogenous retrovirus (BaEV) belongs to a large, widely dispersed interference group that includes the RD114 feline endogenous virus and primate type D retroviruses. Recently, we and another laboratory independently cloned a human receptor for these viruses and identified it as the human sodium-dependent neutral amino acid transporter type 2 (hASCT2). Interestingly, mouse and rat cells are efficiently infected by BaEV but only become susceptible to RD114 and type D retroviruses if the ...[more]

PMID: 10933718

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Project description:BackgroundSkeletal muscle mass and function are partly maintained by the supply of amino acids, altered amino acid transport is an important cause of frailty that can lead to decreased independence with increasing age and slow trauma recovery. The system-A sodium coupled neutral amino acid transporter (SNAT)-2 coded by gene family SLC38A2 generates a 506 amino acid 56 kDa protein that is an important transporter of amino acids in skeletal muscle. Ageing is associated with a decrease in expression of SNAT2 transporters.MethodsIn this study, we used the C2C12 cell line, using myoblast cells and cells differentiated into myotubes. We investigated if the expression of SNAT2 DNA would enhance intracellular amino acid levels and increase their availability for protein synthesis.ResultsIn control myoblasts and myotubes, we found significantly decreased expression of SNAT2 (6.5× decrease, n = 4 per group, P < 0.05) in myotubes than found in myoblasts. After transfection with a SNAT2-eGFP cDNA plasmid, C2C12 myoblasts significantly increased perinuclear punctate SNAT2-eGFP expression that persisted and was more cytoplasmic after differentiation into myotubes. Interestingly, transfected cells were significantly more responsive to the hormone 5α-dihydrotestosterone (DHT, 4.5 nM, by 1.6×, n = 3 per group, P < 0.04). Starvation significantly enhanced the amino acid C14 -MeAIB transport (1.7×, n = 3 per group, P < 0.05) indicating increased function of SNAT2. Inhibiting SNAT2 with high concentrations of MeAIB (3.3 or 5 mM) significantly reduced C14 -Isoleucine transport by L-type amino acid transporter (LAT2, 52.8% and 77%, respectively, n = 3 per group, P < 0.05). However, there was no increase in the LAT2 transport of C14 -isoleucine detectable in SNAT2-eGFP transfected cells after DHT (4.5 nM) exposure. This indicated that small amino acid availability was not rate limiting to LAT2 function in myoblasts.ConclusionsOverall, these data show that transfection of SNAT2-eGFP expression enhanced its function following starvation and treatment with physiological levels of DHT. Enhanced SNAT2 expression in muscle cells offers a viable epigenetic target in pathological conditions associated with altered amino acid transport.

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Sodium-dependent neutral amino acid transporter type 1 is an auxiliary receptor for baboon endogenous retrovirus.

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Sodium-dependent neutral amino acid transporter type 1 is an auxiliary receptor for baboon endogenous retrovirus.

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