384. Species B Adenovirus and Hematopoietic Cells Revisited

• Published in: Molecular therapy Vol. 13; no. S1; p. S146
• Main Authors: Wadell, Goeran, Segerman, Anna, Burmeister, William, Cusack, Steven, Andersson, Emma, Edlund, Karin, Papareddy, Praveen, Gustafsson, Dan, Lindman, Kristina, Marttila, Marko, Skog, Johan, Arnberg, Niklas, Mei, Ya-fang
• Format: Journal Article
• Language: English
• Published: Milwaukee Elsevier Limited 01.05.2006
• Subjects: Adenoviruses; Gene therapy; Medicine; Polyethylene glycol; Thrombocytopenia; Vectors (Biology)
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2006.08.444

Background: Adenoviruses of species A, B, C, D, E and F differ in tropism. In order to address the molecular determinants of adenovirus tropism the distribution of adenovirus receptors on cells of hematopoietic and endothelial origin, and the expression in these cells was assessed.Results: The receptors for species B adenoviruses were most abundantly expressed. CAR binding amino acid residues are not conserved in their fiber knobs consequently CAR can not be used as a receptor. Virions of Ad11p, Ad35 & Ad3 (species B) showed high- affinity to CD34 (+) cells, Ad7, Ad11a (species B) and Ad37 (species D) showed intermediate affinity whereas Ad4 (species E), Ad5 (species C), Ad31 (species A) and Ad41 (species F) hardly bound to CD34 hematopoietic progenitor cells. Only species B and species D adenovirus were expressed in these cells. Based on DNA homology two groups are defined within species B. Ad3, 7, 16, 21 (B:1), and Ad11, 14, 34, 35 and 50 (B:2). Ad3 and Ad7 cause acute respiratory tract infections, whereas Ad11, 34 and 35 cause persistent infections of the urinary tract. We suggest two different receptors for species B adenoviruses: sBAR common to species B members and sB2AR unique for Ad11 and Ad35 members of species B:2. Ad11 virions blocked the binding of Ad3 or Ad7 species B to 70%, whereas Ad3 blocked the binding of Ad11 and Ad35 only partially 30%. sBAR is sensitive to trypsin and EDTA treatment of A549 cells or J82 cells whereas sB2AR is resistent. The binding of Ad3 and Ad7 was restored with Ca ++ . Non permissive chinese hamster ovary (CHO) cells were transfected with the BC1 or BC2 isoforms of CD46 - cDNA. Ad11 virions did but Ad5 virions did not bind to CD46 transfected CHO cells. Adenovirus 11 and 35 can attach and infect primary lymphocytes and monocytes but hexon expression in T- cells required prior activation, whereas neither Ad3, Ad7 nor Ad5 were expressed in the primary PBMCs. Assessment of the transduction ability of established hematopoietic cell lines by a species B vector revealed that Jurkat, U937 and K562 were more efficiently transduced than DG75 cells.EKC causing Ad37 (species D) uses 2-3 linked sialic acid as a primarily functional receptor. The structure of the fiber knob of Ad37 and Ad19p was resolved at 1.5-2Å by W. Burmeister using X-ray crystallography. The binding site for sialyl lactose was identified on the top of the knob close to the 3-fold axis of the trimer. NB Ad37 infects CD34 + cellsConclusion: Species B and D adenovirus using CD46 and 2-3- linked sialic acid as receptors, respectively, infected hematopoietic progenitor cells. Ad11 and Ad35 were more efficient than all other assessed adenoviruses.