Identification of the Myelin Protein Plasmolipin as the Cell Entry Receptor for<i>Mus caroli</i>Endogenous Retrovirus

Miller, A. Dusty; Bergholz, Ulla; Ziegler, Marion; Stocking, Carol

doi:10.1128/jvi.00397-08

Cited by 22 publications

(17 citation statements)

References 44 publications

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“…It is an amino acid transporter ubiquitously expressed in most human tissues, including the placenta, where it is expressed mainly in the cytotrophoblasts (18)(19)(20). Here, we report on the identification of the syncytin-2 receptor via the use of a human/hamster radiation hybrid panel (21, see also [22][23][24]. The identified gene is a receptor with multiple membranespanning domains that can mediate cell-cell fusion and infection by retroviral pseudotypes bearing syncytin-2.…”

mentioning

confidence: 99%

A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2

Esnault

Priet

Ribet

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

188

156

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Syncytin-2 is an envelope gene from the human endogenous retrovirus FRD (HERV-FRD) co-opted by an ancestral primate host, conserved in evolution over >40 Myr, specifically expressed in the placenta, and with a cell-cell fusogenic activity likely contributing to placenta morphogenesis. Here, using the GeneBridge4 human/Chinese hamster radiation hybrid panel, we mapped and identified the human receptor for syncytin-2. This receptor-namely Major Facilitator Superfamily Domain Containing 2 (MFSD2)-belongs to a large family of presumptive carbohydrate transporters with 10 -12 membrane-spanning domains, is located at chromosomal position 1p34.2, and is conserved in evolution. An expression vector for MFSD2 confers fusogenicity to otherwise insusceptible cells upon transfection of syncytin-2. It also confers infectivity to syncytin-2 pseudotypes, consistent with this protein being the receptor for the ancestrally acquired HERV-FRD family of endogenous retroviruses. At variance with the human gene, neither mouse nor rat MFSD2 can mediate membrane fusion, which is consistent with the fact that the envelope-derived syncytin genes co-opted by rodents during evolution are not orthologous to the human syncytin genes. Remarkably, a real-time quantitative RT-PCR analysis of MFSD2 in various human tissues demonstrates specific expression in the placenta, as well as in the human BeWo choriocarcinoma cell line, which discloses enhancement of receptor expression upon induction by forskolin of cell-cell fusion and syncytium formation. In situ hybridization of human placental tissue using an MFSD2-specific probe further unambiguously demonstrates receptor expression at the level of the syncytiotrophoblast, again consistent with a role in placenta morphogenesis.envelope protein ͉ human endogenous retrovirus (HERV) ͉ major facilitator superfamily domain containing 2 (MFSD2) ͉ syncytiotrophoblast T he placenta is an autonomous and transient organ essentially aimed at mediating nutrient and gas exchange between mother and fetus during intrauterine life. In several mammalian species with a hemochorial placenta-including human-a key process of placental morphogenesis is the fusion of trophoblastic cells into a multinucleated layer called syncytiotrophoblast, which constitutes the main materno-fetal barrier in direct contact with maternal blood and fulfils essential trophic exchange functions (1-3).Little is known about the molecular mechanisms involved in trophoblastic differentiation. However, a major advance has been made by the identification of envelope (Env) proteins encoded by endogenous retroviruses (ERVs) and likely involved in the formation of the syncytiotrophoblast (4-8). The mammalian genomes indeed harbor thousands of ERV elements that display a structure close to that of the integrated proviral form of exogenous retroviruses (gag, pol, and env-related regions flanked by 2 long terminal repeats) and most probably are the remnants of past infections of the germ line by ancestral retroviruses (9, 10). Although the vast majority...

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mentioning

confidence: 99%

A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2

Esnault

Priet

Ribet

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

188

156

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“…PLLP is mainly a plasma membrane protein that recycles through Golgi membranes through a tubular endocytic organelle. Its recycling from the plasma membrane is supported by the findings that it serves as a mouse viral receptor (Miller et al, 2008) and that it cofractionates with endocytic markers (Sapirstein et al, 1992b). Recently PLLP has been demonstrated to regulate epithelial development through the regulation of endocytosis in zebrafish (Rodríguez-Fraticelli et al, 2015).…”

Section: Discussionmentioning

confidence: 53%

The myelin proteolipid plasmolipin forms oligomers and induces liquid-ordered membranes in the Golgi complex

Yaffe

Hugger

Yassaf

et al. 2015

Journal of Cell Science

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Myelin comprises a compactly stacked massive surface area of protein-poor thick membrane that insulates axons to allow fast signal propagation. Increasing levels of the myelin protein plasmolipin (PLLP) were correlated with post-natal myelination; however, its function is unknown. Here, the intracellular localization and dynamics of PLLP were characterized in primary glial and cultured cells using fluorescently labeled PLLP and antibodies against PLLP. PLLP localized to and recycled between the plasma membrane and the Golgi complex. In the Golgi complex, PLLP forms oligomers based on fluorescence resonance energy transfer (FRET) analyses. PLLP oligomers blocked Golgi to plasma membrane transport of the secretory protein vesicular stomatitis virus G protein (VSVG), but not of a VSVG mutant with an elongated transmembrane domain. Laurdan staining analysis showed that this block is associated with PLLPinduced proliferation of liquid-ordered membranes. These findings show the capacity of PLLP to assemble potential myelin membrane precursor domains at the Golgi complex through its oligomerization and ability to attract liquid-ordered lipids. These data support a model in which PLLP functions in myelin biogenesis through organization of myelin liquid-ordered membranes in the Golgi complex.

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“…This is consistent with the lack of detection of any GALV-like sequence in this species. McERV sequences were detected, but this virus uses a different receptor from the one used by GALV (23). However, GALV could potentially infect Mus caroli using PiT2, given its identity to Mus musculus molossinus PiT2, which is a functional GALV receptor.…”

Section: Discussionmentioning

confidence: 99%

“…However, these reports were based on DNA hybridization techniques, and sequences were not reported. In 2008, the full genome sequence of an endogenous retrovirus found in the genome of Mus caroli (McERV) was reported (23). Despite the relatively high similarity of its genomic sequence to those of GALV and KoRV, McERV has a different host range and uses a different receptor, and therefore it is unlikely to be a progenitor of GALV and KoRV (23).…”

mentioning

confidence: 99%

“…In 2008, the full genome sequence of an endogenous retrovirus found in the genome of Mus caroli (McERV) was reported (23). Despite the relatively high similarity of its genomic sequence to those of GALV and KoRV, McERV has a different host range and uses a different receptor, and therefore it is unlikely to be a progenitor of GALV and KoRV (23). McERV is most closely related to the Mus dunni endogenous virus (MDEV) (24) and the Mus musculus endogenous retrovirus (MmERV) (25), which together form a sister clade to the KoRV/GALV clade (2).…”

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confidence: 99%

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Endogenous Gibbon Ape Leukemia Virus Identified in a Rodent (Melomys burtoni subsp.) from Wallacea (Indonesia)

Alfano

Michaux

Morand

et al. 2016

J Virol

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Gibbon ape leukemia virus (GALV) and koala retrovirus (KoRV) most likely originated from a cross-species transmission of an ancestral retrovirus into koalas and gibbons via one or more intermediate as-yet-unknown hosts. A virus highly similar to GALV has been identified in an Australian native rodent (Melomys burtoni) after extensive screening of Australian wildlife. GALV-like viruses have also been discovered in several Southeast Asian species, although screening has not been extensive and viruses discovered to date are only distantly related to GALV. We therefore screened 26 Southeast Asian rodent species for KoRV-and GALV-like sequences, using hybridization capture and high-throughput sequencing, in the attempt to identify potential GALV and KoRV hosts. Only the individuals belonging to a newly discovered subspecies of Melomys burtoni from Indonesia were positive, yielding an endogenous provirus very closely related to a strain of GALV. The sequence of the critical receptor domain for GALV infection in the Indonesian M. burtoni subsp. was consistent with the susceptibility of the species to GALV infection. The second record of a GALV in M. burtoni provides further evidence that M. burtoni, and potentially other lineages within the widespread subfamily Murinae, may play a role in the spread of GALV-like viruses. The discovery of a GALV in the most western part of the Australo-Papuan distribution of M. burtoni, specifically in a transitional zone between Asia and Australia (Wallacea), may be relevant to the cross-species transmission to gibbons in Southeast Asia and broadens the known distribution of GALVs in wild rodents. IMPORTANCEGibbon ape leukemia virus (GALV) and the koala retrovirus (KoRV) are very closely related, yet their hosts neither are closely related nor overlap geographically. Direct cross-species infection between koalas and gibbons is unlikely. Therefore, GALV and KoRV may have arisen via a cross-species transfer from an intermediate host whose range overlaps those of both gibbons and koalas. Using hybridization capture and high-throughput sequencing, we have screened a wide range of rodent candidate hosts from Southeast Asia for KoRV-and GALV-like sequences. Only a Melomys burtoni subspecies from Wallacea (Indonesia) was positive for GALV. We report the genome sequence of this newly identified GALV, the critical domain for infection of its potential cellular receptor, and its phylogenetic relationships with the other previously characterized GALVs. We hypothesize that Melomys burtoni, and potentially related lineages with an Australo-Papuan distribution, may have played a key role in crossspecies transmission to other taxa. The evolutionary mechanisms involved in cross-species transmissions (CSTs) of viruses are complex and generally poorly understood. Viral evolution, host contact rates, biological similarity in host defense systems (receptors, viral restriction factors), and host evolutionary relationships have been proposed as key factors in CST rates and outcomes (1). However, the...

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Identification of the Myelin Protein Plasmolipin as the Cell Entry Receptor forMus caroliEndogenous Retrovirus

Cited by 22 publications

References 44 publications

A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2

A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2

The myelin proteolipid plasmolipin forms oligomers and induces liquid-ordered membranes in the Golgi complex

Endogenous Gibbon Ape Leukemia Virus Identified in a Rodent (Melomys burtoni subsp.) from Wallacea (Indonesia)

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