Structure of a Protozoan Virus from the Human Genitourinary Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>

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 g...

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Autores principales:	Kristin N. Parent, Yuko Takagi, Giovanni Cardone, Norman H. Olson, Maria Ericsson, May Yang, Yujin Lee, John M. Asara, Raina N. Fichorova, Timothy S. Baker, Max L. Nibert
Formato:	article
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Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0d3db788b4904565a0ae4780d942dc15
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spelling	oai:doaj.org-article:0d3db788b4904565a0ae4780d942dc152021-11-15T15:40:28ZStructure of a Protozoan Virus from the Human Genitourinary Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>10.1128/mBio.00056-132150-7511https://doaj.org/article/0d3db788b4904565a0ae4780d942dc152013-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00056-13https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Trichomonas vaginalis causes ~250 million new cases of sexually transmitted disease each year worldwide and is associated with serious complications, including premature birth and increased transmission of other pathogens, including HIV. It is an extracellular parasite that, in turn, commonly hosts infections with double-stranded RNA (dsRNA) viruses, trichomonasviruses, which appear to exacerbate disease through signaling of immunoinflammatory responses by human epithelial cells. Here we report the first three-dimensional structure of a trichomonasvirus, which is also the first such structure of any protozoan dsRNA virus; show that it has unusually wide channels at the capsid vertices, with potential for releasing the viral genome and promoting dsRNA-dependent responses by human cells; and provide evidence that it uses −2 ribosomal frameshifting, an uncommon mechanism, to translate its RNA polymerase in fusion with its capsid protein. These findings provide both mechanistic and translational insights concerning the role of trichomonasviruses in aggravating disease attributable to T. vaginalis.Kristin N. ParentYuko TakagiGiovanni CardoneNorman H. OlsonMaria EricssonMay YangYujin LeeJohn M. AsaraRaina N. FichorovaTimothy S. BakerMax L. NibertAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 2 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Kristin N. Parent Yuko Takagi Giovanni Cardone Norman H. Olson Maria Ericsson May Yang Yujin Lee John M. Asara Raina N. Fichorova Timothy S. Baker Max L. Nibert Structure of a Protozoan Virus from the Human Genitourinary Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
description	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. IMPORTANCE Trichomonas vaginalis causes ~250 million new cases of sexually transmitted disease each year worldwide and is associated with serious complications, including premature birth and increased transmission of other pathogens, including HIV. It is an extracellular parasite that, in turn, commonly hosts infections with double-stranded RNA (dsRNA) viruses, trichomonasviruses, which appear to exacerbate disease through signaling of immunoinflammatory responses by human epithelial cells. Here we report the first three-dimensional structure of a trichomonasvirus, which is also the first such structure of any protozoan dsRNA virus; show that it has unusually wide channels at the capsid vertices, with potential for releasing the viral genome and promoting dsRNA-dependent responses by human cells; and provide evidence that it uses −2 ribosomal frameshifting, an uncommon mechanism, to translate its RNA polymerase in fusion with its capsid protein. These findings provide both mechanistic and translational insights concerning the role of trichomonasviruses in aggravating disease attributable to T. vaginalis.
format	article
author	Kristin N. Parent Yuko Takagi Giovanni Cardone Norman H. Olson Maria Ericsson May Yang Yujin Lee John M. Asara Raina N. Fichorova Timothy S. Baker Max L. Nibert
author_facet	Kristin N. Parent Yuko Takagi Giovanni Cardone Norman H. Olson Maria Ericsson May Yang Yujin Lee John M. Asara Raina N. Fichorova Timothy S. Baker Max L. Nibert
author_sort	Kristin N. Parent
title	Structure of a Protozoan Virus from the Human Genitourinary Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_short	Structure of a Protozoan Virus from the Human Genitourinary Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_full	Structure of a Protozoan Virus from the Human Genitourinary Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_fullStr	Structure of a Protozoan Virus from the Human Genitourinary Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_full_unstemmed	Structure of a Protozoan Virus from the Human Genitourinary Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_sort	structure of a protozoan virus from the human genitourinary parasite <named-content content-type="genus-species">trichomonas vaginalis</named-content>
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/0d3db788b4904565a0ae4780d942dc15
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Structure of a Protozoan Virus from the Human Genitourinary Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>

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