Role of sialic acid-containing molecules and the α4β1 integrin receptor in the early steps of polyomavirus infection

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Abstract
Murine polyomavirus (MPyV) infection occurs through recognition of sialic acid (SA) residues present on the host cell membrane, but the nature of the molecules involved and the exact role of this interaction in virus cell entry still need to be clarified. In this work, mutations at residues R77 or H298 of the MPyV VP1 protein were shown to lead to a complete loss of virus infectivity, which, however, could be restored by lipofection of virus particles into the cytoplasm of the host cells. Using virus-like particles (VLPs), it was demonstrated that the non-infectivity of these mutants was due to impaired cell entry caused by total abrogation of SA-dependent cell binding. This indicates that SA residues are essential primary cell receptors for MPyV. As the α4β1 integrin has been identified recently as a cell receptor for MPyV, the relationship, if any, was investigated between SA-containing and α4β1 integrin receptors. The ability of mutants R77Q and H298Q and wt VLPs to bind to cells overexpressing the α4β1 integrin was studied in SA-positive (BALB/c 3T3 cells and Pro-5 cells) and SA-deficient (Pro5-derived Lec-2 cells) backgrounds. Overexpression of α4β1 integrin did not restore binding of mutant VLPs in any of these cell lines or, indeed, that of wt VLPs in a SA-deficient background. Moreover, evidence is provided that overexpression of the sialylated α4β1 integrin enhances wt VLP cell binding, suggesting that, in addition to its function at a post-attachment level, α4β1 integrin acts also as one of the SA-containing receptors for initial cell binding.