title: Structure of a protozoan virus from the human genitourinary parasite Trichomonas vaginalis.
abstract: The flagellated protozoan Trichomonas vaginalis is an obligate human genitourinary parasite and the most frequent cause of sexually transmitted disease worldwide. Most clinical isolates of T. vaginalis are persistently infected with one or more double-stranded RNA (dsRNA) viruses from the genus Trichomonasvirus, family Totiviridae, which appear to influence not only protozoan biology but also human disease. Here we describe the three-dimensional structure of Trichomonas vaginalis virus 1 (TVV1) virions, as determined by electron cryomicroscopy and icosahedral image reconstruction. The structure reveals a T = 1 capsid comprising 120 subunits, 60 in each of two nonequivalent positions, designated A and B, as previously observed for fungal Totiviridae family members. The putative protomer is identified as an asymmetric AB dimer consistent with either decamer or tetramer assembly intermediates. The capsid surface is notable for raised plateaus around the icosahedral 5-fold axes, with canyons connecting the 2- and 3-fold axes. Capsid-spanning channels at the 5-fold axes are unusually wide and may facilitate release of the viral genome, promoting dsRNA-dependent immunoinflammatory responses, as recently shown upon the exposure of human cervicovaginal epithelial cells to either TVV-infected T. vaginalis or purified TVV1 virions. Despite extensive sequence divergence, conservative features of the capsid reveal a helix-rich fold probably derived from an ancestor shared with fungal Totiviridae family members. Also notable are mass spectrometry results assessing the virion proteins as a complement to structure determination, which suggest that translation of the TVV1 RNA-dependent RNA polymerase in fusion with its capsid protein involves -2, and not +1, ribosomal frameshifting, an uncommonly found mechanism to date.
authors.affiliation: Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Parent
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takagi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cardone
authors.forename: Norman H
authors.initials: NH
authors.lastname: Olson
authors.forename: Maria
authors.initials: M
authors.lastname: Ericsson
authors.forename: May
authors.initials: M
authors.lastname: Yang
authors.forename: Yujin
authors.initials: Y
authors.lastname: Lee
authors.forename: John M
authors.initials: JM
authors.lastname: Asara
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Baker
authors.forename: Max L
authors.initials: ML
authors.lastname: Nibert
mesh_terms: D000595:Amino Acid Sequence; D002213:Capsid / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D006801:Humans; D021621:Imaging, Three-Dimensional; D008969:Molecular Sequence Data; D019196:Totiviridae / Q000302:isolation & purification / Q000648:ultrastructure*; D014246:Trichomonas vaginalis / Q000821:virology*; D014771:Virion / Q000302:isolation & purification / Q000648:ultrastructure*
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