The Envelope Glycoprotein of Human Endogenous Retrovirus Type W Uses a Divergent Family of Amino Acid Transporters/Cell Surface Receptors

Lavillette, Dimitri; Marin, Mariana; Ruggieri, Alessia; Mallet, François; Cosset, François‐Loïc; Kabat, David

doi:10.1128/jvi.76.13.6442-6452.2002

Cited by 169 publications

(167 citation statements)

References 62 publications

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“…Syncytin, the envelope protein of one of the defective HERV-W proviruses is obviously essential for the formation and function of syncytiotrophoblasts (84)(85)(86)(87). These multinucleated cells originate from fetal trophoblasts and constitute the boundary layer between maternal and fetal tissue.…”

Section: Biological Implications Of Retroelement Inheritancementioning

confidence: 99%

Retroelements and the human genome: New perspectives on an old relation

Bannert

Kurth

2004

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

466

423

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Retroelements constitute a large portion of our genomes. One class of these elements, the human endogenous retroviruses (HERVs), is comprised of remnants of ancient exogenous retroviruses that have gained access to the germ line. After integration, most proviruses have been the subject of numerous amplifications and have suffered extensive deletions and mutations. Nevertheless, HERV-derived transcripts and proteins have been detected in healthy and diseased human tissues, and HERV-K, the youngest, most conserved family, is able to form virus-like particles. Although it is generally accepted that the integration of retroelements can cause significant harm by disrupting or disregulating essential genes, the role of HERV expression in the etiology of malignancies and autoimmune and neurologic diseases remains controversial. In recent years, striking evidence has accumulated indicating that some proviral sequences and HERV proteins might even serve the needs of the host and are therefore under positive selection. The remarkable progress in the analysis of host genomes has brought to light the significant impact of HERVs and other retroelements on genetic variation, genome evolution, and gene regulation.A lmost half of the mammalian genome is derived from ancient transposable elements. The two general types, (DNA)-transposons and retroelements, often regarded as ''selfish DNA parasites or junk DNA,'' encompass Ϸ2.8% and 42.2% of the human genome, respectively (1, 2). This striking finding is one of the many insights from recent large-scale sequencing projects that have provided the most valuable information in this field since the initial discovery of mobile elements in 1956 by Barbara McClintock (3, 4). Whereas DNA-transposons amplify without an RNA intermediate, retroelements rely on an RNA transcript that is retrotranscribed by a reverse transcriptase before integration in the genome. Here, we briefly review the characteristics of retroelements, their present classification, and the available evidence for their biological significance and function in normal and pathological processes. The focus is on human endogenous retroviruses (HERVs), the remnants of ancient germ-cell infections. Although most of the HERV proviruses have undergone extensive deletions and mutations, some have retained ORFs coding for functional proteins. A few families, including the HERV-K (HML-2) group, have been shown to form viral particles (5, 6), and an apparently intact provirus has recently been discovered in a small fraction of the human population, indicating a very recent acquisition (5-7). Classification of RetroelementsRetroelements constitute 90% of the Ϸ3 million transposable elements present in the human genome (1). They are split into two large groups, the non-LTR and LTR elements (Fig. 1). Two of the non-LTR members are present in extremely high copy numbers in the mammalian germ line: the short interspersed elements (SINE) with the prominent Alu and MIR repeats and the long-terminal interspersed elements (LINE) containing the...

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Section: Biological Implications Of Retroelement Inheritancementioning

confidence: 99%

Retroelements and the human genome: New perspectives on an old relation

Bannert

Kurth

2004

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

466

423

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“…Inhibition of the trophoblast invasion may lead to diseases like preeclampsia; uncontrolled invasion may lead to placenta accreta, increta or even percreta ( [Knerr et al, 2002] and [Lavillette et al, 2002]). …”

Section: Potential Immunosuppressive Function Of Herv-k In the Placentamentioning

confidence: 99%

“…In addition, ERV-3 ( [Boyd et al, 1993] and [Venables et al, 1995]) and HERV-E (Yi and Kim, 2007) were also found to be expressed in placental tissue. While syncytin-1 interacts with the D type mammalian retrovirus receptor (ASCT2) ( [Blond et al, 2000] and [Lavillette et al, 2002]), which is mainly expressed in VT cells (Hayward et al, 2007), the receptor of syncytin-2 (MFSD2) is specifically expressed in the syncytiotrophoblast (Esnault et al, 2008). Syncytin-1 was shown to mediate the fusion of the villous cytotrophoblast to form the multinucleated syncytiotrophoblast ( [Blond et al, 2000] and [Frendo et al, 2003]).…”

Section: Introductionmentioning

confidence: 99%

Human endogenous retrovirus K (HERV-K) is expressed in villous and extravillous cytotrophoblast cells of the human placenta

Kämmerer

Germeyer

Stengel

et al. 2011

Journal of Reproductive Immunology

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Human endogenous retroviruses (HERVs) expression of another HERV, HERV-K, which is characterised by open reading frames for all viral genes. Using immunohistochemistry and Western blot analysis, expression of the transmembrane envelope (TM) protein of HERV-K was studied in normal placental and decidual tissues obtained at different gestational ages. The TM protein was expressed exclusively in villous (VT) and extravillous cytotrophoblast (EVT) cells, but not in the syncytiotrophoblast or other cells. The expression of the TM protein of HERV-K in EVT cells was confirmed by Western blot analysis of isolated c-erbB2-expressing cytotrophoblast cells. Thus, this is

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“…Interestingly, several transporters also function as receptors for different neurotropic retroviruses (4). The human endogenous retrovirus (HERV-W) envelope glycoprotein, Syncytin-1, binds to two receptors including the sodium-dependent transporters of polar neutral amino acids, alanine, serine, cysteine, and threonine (ASCT1 and ASCT2) (4), which are localized on both neurons and glia (5) and are known to modulate both neurotrophic (6) and neurotoxic (7) effects in the CNS.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

The Human Endogenous Retrovirus Envelope Glycoprotein, Syncytin-1, Regulates Neuroinflammation and Its Receptor Expression in Multiple Sclerosis: A Role for Endoplasmic Reticulum Chaperones in Astrocytes

Antony

Ellestad

Hammond

et al. 2007

The Journal of Immunology

126

125

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Retroviral envelopes are pathogenic glycoproteins which cause neuroinflammation, neurodegeneration, and endoplasmic reticulum stress responses. The human endogenous retrovirus (HERV-W) envelope protein, Syncytin-1, is highly expressed in CNS glia of individuals with multiple sclerosis (MS). In this study, we investigated the mechanisms by which Syncytin-1 mediated neuroimmune activation and oligodendrocytes damage. In brain tissue from individuals with MS, ASCT1, a receptor for Syncytin-1 and a neutral amino acid transporter, was selectively suppressed in astrocytes (p < 0.05). Syncytin-1 induced the expression of the endoplasmic reticulum stress sensor, old astrocyte specifically induced substance (OASIS), in cultured astrocytes, similar to findings in MS brains. Overexpression of OASIS in astrocytes increased inducible NO synthase expression but concurrently down-regulated ASCT1 (p < 0.01). Treatment of astrocytes with a NO donor enhanced expression of early growth response 1, with an ensuing reduction in ASCT1 expression (p < 0.05). Small-interfering RNA molecules targeting Syncytin-1 selectively down-regulated its expression, preventing the suppression of ASCT1 and the release of oligodendrocyte cytotoxins by astrocytes. A Syncytin-1-transgenic mouse expressing Syncytin-1 under the glial fibrillary acidic protein promoter demonstrated neuroinflammation, ASCT1 suppression, and diminished levels of myelin proteins in the corpus callosum, consistent with observations in CNS tissues from MS patients together with neurobehavioral abnormalities compared with wild-type littermates (p < 0.05). Thus, Syncytin-1 initiated an OASIS-mediated suppression of ASCT1 in astrocytes through the induction of inducible NO synthase with ensuing oligodendrocyte injury. These studies provide new insights into the role of HERV-mediated neuroinflammation and its contribution to an autoimmune disease.

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The Envelope Glycoprotein of Human Endogenous Retrovirus Type W Uses a Divergent Family of Amino Acid Transporters/Cell Surface Receptors

Cited by 169 publications

References 62 publications

Retroelements and the human genome: New perspectives on an old relation

Retroelements and the human genome: New perspectives on an old relation

Human endogenous retrovirus K (HERV-K) is expressed in villous and extravillous cytotrophoblast cells of the human placenta

The Human Endogenous Retrovirus Envelope Glycoprotein, Syncytin-1, Regulates Neuroinflammation and Its Receptor Expression in Multiple Sclerosis: A Role for Endoplasmic Reticulum Chaperones in Astrocytes

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