Primary attachment of murine leukaemia virus vector mediated by particle-associated heparan sulphate proteoglycan

Nina Kureishy , Daisy Faruque , Colin D Porter (1)

1 Cell and Molecular Biology

Target cell entry of murine leukaemia virus vectors proceeds via primary attachment, independent of the viral envelope protein, and subsequent envelope/receptor interaction. Whilst much attention has been paid to modifying the latter for target cell specificity the initial binding interaction has been overlooked, despite its opposing involvement both in providing the virus available for receptor binding and in depleting free virus. As a first step towards modifying primary attachment, both to provide specificity and to enhance vector availability, we sought to determine the nature of this interaction. Following an initial screen of glycosaminoglycans for their ability to inhibit virus binding and transduction we have shown that production of virus from cells in which glycosaminoglycan-sulphation is inhibited, or treatment of virus with heparinase III, reduces both particle attachment and infection. Detection in purified virus preparations of a neo-epitope generated by heparinase III confirmed the presence of virus-associated heparan sulphate proteoglycan, acquired from the producer cell. We propose that host-acquired cell surface heparan sulphate proteoglycan (potentially including syndecan-2) provides a means of virus attachment to target cells that precedes specific receptor interaction and membrane fusion. Inhibition of heparan sulphate biosynthesis may provide a sufficiently reduced background of primary binding such that novel mechanisms of attachment, ideally with appropriate target cell-specificity, can be introduced.

Mots clés: Life Sciences

Nina Kureishy, Daisy Faruque, Colin D Porter. Primary attachment of murine leukaemia virus vector mediated by particle-associated heparan sulphate proteoglycan. Biochemical Journal, 2006, 400 (3), pp.421-430. ⟨10.1042/BJ20060825⟩. ⟨hal-00478609⟩