title: Mutation in the VP1-LDV motif of the murine polyomavirus affects viral infectivity and conditions virus tissue tropism in vivo.
abstract: The first contact of a virus with the host cell surface and further entry are important steps for a successful outcome of the infection process and for the virus-associated pathogenicity. We have previously shown that the entry of the murine Polyomavirus (Py) into fibroblasts is a multi-step process involving, at least, the attachment to primary sialic acids (SA)-containing cell receptors followed by post-binding interaction with secondary receptors, such as the alpha4beta1 integrin, likely through the VP1-LDV motif. Here we report on the functional role of the VP1-LDV motif in Py infectivity and in vivo virus tissue tropism. For this purpose, we have characterized a recombinant virus mutant, PyLNV, harboring a single aa substitution in this motif (D138N). Although not critical for virus viability, the D138N substitution abrogates the post-attachment Py-alpha4beta1 interaction, rendering the PyLNV mutant virus twofold less infectious than the Py wild-type (Wt) in alpha4beta1-positive fibroblasts. To study the putative role of the VP1-LDV motif in vivo, newborn C57BL/6 mice were inoculated with PyWt or PyLNV and, after six days, organs were analyzed for the presence of viral DNA. Intriguingly, PyLNV showed an altered spectrum of in vivo replication compared with PyWt, particularly in the skin and in the kidney. The implication of Py-alpha4beta1 integrin interaction in conditioning tissue-specificity of virus replication is discussed.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy. madda.caruso@gmail.com
authors.forename: Maddalena
authors.initials: M
authors.lastname: Caruso
authors.forename: Anna
authors.initials: A
authors.lastname: Busanello
authors.forename: Olga
authors.initials: O
authors.lastname: Sthandier
authors.forename: Michaela
authors.initials: M
authors.lastname: Cavaldesi
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Marie Isabelle
authors.initials: MI
authors.lastname: Garcia
authors.forename: Paolo
authors.initials: P
authors.lastname: Amati
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011120:Polyomavirus / Q000235:genetics / Q000472:pathogenicity*; D018523:Tropism / Q000235:genetics*; D014774:Virulence / Q000235:genetics*
chemical_list: D036022:Capsid Proteins; C062481:VP1 protein, polyomavirus