PMID- 34711462 OWN - NLM STAT- MEDLINE DCOM- 20220414 LR - 20220603 IS - 1878-4380 (Electronic) IS - 0966-842X (Linking) VI - 30 IP - 5 DP - 2022 May TI - Adeno-associated virus (AAV) cell entry: structural insights. PG - 432-451 LID - S0966-842X(21)00216-X [pii] LID - 10.1016/j.tim.2021.09.005 [doi] AB - Adeno-associated virus (AAV) is the leading vector in emerging treatments of inherited diseases. Higher transduction efficiencies and cellular specificity are required for broader clinical application, motivating investigations of virus-host molecular interactions during cell entry. High-throughput methods are identifying host proteins more comprehensively, with subsequent molecular studies revealing unanticipated complexity and serotype specificity. Cryogenic electron microscopy (cryo-EM) provides a path towards structural details of these sometimes heterogeneous virus-host complexes, and is poised to illuminate more fully the steps in entry. Here presented, is progress in understanding the distinct steps of glycan attachment, and receptor-mediated entry/trafficking. Comparison with structures of antibody complexes provides new insights on immune neutralization with implications for the design of improved gene therapy vectors. CI - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Meyer, Nancy L AU - Meyer NL AD - Pacific Northwest Cryo-EM Center, Oregon Health and Science University (OHSU) Center for Spatial Systems Biomedicine, Portland, OR, USA. FAU - Chapman, Michael S AU - Chapman MS AD - Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA. Electronic address: chapmanms@missouri.edu. LA - eng GR - R35 GM122564/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review DEP - 20211025 PL - England TA - Trends Microbiol JT - Trends in microbiology JID - 9310916 RN - 0 (Polysaccharides) RN - 0 (Receptors, Cell Surface) SB - IM MH - *Dependovirus/genetics/metabolism MH - Genetic Vectors MH - Polysaccharides/metabolism MH - Receptors, Cell Surface/genetics MH - Serogroup MH - *Virus Internalization OTO - NOTNLM OT - AAVR OT - antibody OT - attachment OT - gene therapy OT - glycan OT - receptor COIS- Declaration of interests There are no interests to declare. EDAT- 2021/10/30 06:00 MHDA- 2022/04/15 06:00 CRDT- 2021/10/29 05:44 PHST- 2021/06/16 00:00 [received] PHST- 2021/09/02 00:00 [revised] PHST- 2021/09/14 00:00 [accepted] PHST- 2021/10/30 06:00 [pubmed] PHST- 2022/04/15 06:00 [medline] PHST- 2021/10/29 05:44 [entrez] AID - S0966-842X(21)00216-X [pii] AID - 10.1016/j.tim.2021.09.005 [doi] PST - ppublish SO - Trends Microbiol. 2022 May;30(5):432-451. doi: 10.1016/j.tim.2021.09.005. Epub 2021 Oct 25.