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Capture in the metabolic arena: co-selection of gamma and deltaretrovirus envelope glycoproteins and their receptors

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Capture in the metabolic arena: co-selection of gamma

and deltaretrovirus envelope glycoproteins and their

receptors

Marc Sitbon, Hiroyuki Abe, Valérie Courgnaud, Donatella Giovannini, Felix

Kim, Madakasira Lavanya, Nicolas Manel, Jawida Touhami, Wiliam Switzer,

Pierre Castelnau, et al.

To cite this version:

Marc Sitbon, Hiroyuki Abe, Valérie Courgnaud, Donatella Giovannini, Felix Kim, et al.. Capture

in the metabolic arena: co-selection of gamma and deltaretrovirus envelope glycoproteins and their

receptors. Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts, Sep 2009,

Montpellier, France. pp.I20, �10.1186/1742-4690-6-S2-I20�. �inserm-00668488�

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BioMed Central

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Retrovirology

Open Access

Invited speaker presentation

Capture in the metabolic arena: co-selection of gamma and

deltaretrovirus envelope glycoproteins and their receptors

Marc Sitbon*

1

, Hiroyuki Abe

1

, Valérie Courgnaud

1

, Donatella Giovannini

1

,

Felix Kim

1

, Madakasira Lavanya

1

, Nicolas Manel

1

, Jawida Touhami

1

,

Wiliam M Switzer

2

, Pierre Castelnau

3

, Emmanuelle Lagrue

3

, Lydie

Nadal-Desbarats

4

, Karine de Guillen

5

, Christian Roumestand

5

and Jean-Luc Battini

1

Address: 1Institut de Génétique Moléculaire de Montpellier (IGMM), CNRS-UMR 5535, Université Montpellier 1 et 2, IFR 122, 34293 Montpellier

Cedex 5, France, 2Centers for Disease Control and Prevention, Atlanta, Georgia, USA, 3Service de Neurologie et Neurochirurgie Pédiatrique, Centre

de Pédiatrie Gatien-de-Clocheville, CHRU de Tours, 37044 Tours cedex 01 INSERM U930, France, 4INSERM U930, Université François Rabelais

de Tours, 37032 Tours, France and 5Centre de Biochimie Structurale (CBS), UMR UM1/5048 CNRS/554 INSERM, 29 rue de Navacelles, 34090,

Montpellier Cedex, France * Corresponding author

Although all infectious and replication-competent retrovi-ruses harbor an env gene, the origin of env remains unknown except for that of a few invertebrate retroviruses. It is generally admitted that infectious retroviruses have evolved from endogenous viral retrotransposons by inser-tion of an ''external'' gene that encodes for a fusion glyco-protein (env capture). In 2000, Malik et al. provided the first formal evidence for the origin of env in several inver-tebrate retroviruses. For instance, they showed that env of

Gypsy, an infectious Drosophila retrotransposon, has been

''captured'' from a fusion protein-encoding gene of a bac-ulovirus, a totally unrelated large DNA enveloped virus. Vertebrate retroviruses cover 7 genera distinguished by their gag (capsid encoding) and pol (enzyme encoding) genes. The gammaretroviruses (murine leukemia viruses, MLV as a prototype) and deltaretroviruses (the human T cell leukemia virus, HTLV as a prototype) are the most dis-tant genera according to their pol genes. However, we reported that HTLV env is most closely related to MLV env, sharing similar modular organization and motifs even within the receptor-binding domain (RBD), the Env most variable sequence. Accordingly, swapping the RBD-encod-ing regions between the two types of Env yielded

func-tional chimeras. We argued that this common ancestry between the env of remotely related retroviruses is also in favor of an env capture scenario by vertebrate retroviruses. Nonetheless, the origin of these env, and more specifically their RBD, remains unknown.

Based on the gammaretrovirus Env modular organization, we derived soluble RBD domains of different gamma and deltaretroviruses. This has been instrumental to the iden-tification of Glut1, the major glucose transporter, as the cognate receptor of HTLV-1 and 2 Env. We further showed that Glut1 binds all known HTLV or S(imian)TLV types and that intracellular interaction of HTLV or STLV RBD with Glut1 modulates glucose transport and glycolysis. Of most interest is that, like Glut1, all of the receptors identi-fied so far for gammaretrovirus Env belong to the family of multimembrane-spanning molecules and that those for which a function has been determined are all metabolite transporters (amino acids, inorganic phosphate, vitamins, etc.).

The selection as Env receptors of metabolite transporters that shuttles from cytoplasmic pools to the cell surface and the cytoplasmic interaction between RBD and their from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts

Montpellier, France. 21-23 September 2009 Published: 24 September 2009

Retrovirology 2009, 6(Suppl 2):I20 doi:10.1186/1742-4690-6-S2-I20

<supplement> <title> <p>Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</p> </title> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S2-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf</url> </supplement> This abstract is available from: http://www.retrovirology.com/content/6/S2/I20

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cognate receptors have us to postulate that gamma and deltaretrovirus Env, and more particularly their RBD mod-ules, are related to transporter chaperone molecules that modulate their cell surface translocation.

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