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Grant support

This work was supported in part by Public Health Service awards AI032539 (T.S. Dermody and C. Risco), AI122563 (J.J. Knowlton), and GM007347 (J.J. Knowlton).

Analysis of institutional authors

Ortega-Gonzalez, PaulaAuthor

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Article

A modified lysosomal organelle mediates nonlytic egress of reovirus

Publicated to:Journal Of Cell Biology. 219 (7): - 2020-07-06 219(7), DOI: 10.1083/jcb.201910131

Authors: Fernandez de Castro, Isabel; Tenorio, Raquel; Ortega-Gonzalez, Paula; Knowlton, Jonathan J.; Zamora, Paula F.; Lee, Christopher H.; Fernandez, Jose J.; Dermody, Terence S.; Risco, Cristina;

Affiliations

Spanish Natl Res Council, Natl Ctr Biotechnol, Cell Struct Lab, Madrid, Spain - Author
Spanish Natl Res Council, Natl Ctr Biotechnol, Dept Macromol Struct, Madrid, Spain - Author
Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15260 USA - Author
Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA - Author
UPMC Childrens Hosp Pittsburgh, Ctr Microbial Pathogenesis, Pittsburgh, PA 15224 USA - Author
Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA - Author
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Abstract

Mammalian orthoreoviruses (reoviruses) are nonenveloped viruses that replicate in cytoplasmic membranous organelles called viral inclusions (Vis) where progeny virions are assembled. To better understand cellular routes of nonlytic reovirus exit, we imaged sites of virus egress in infected, nonpolarized human brain microvascular endothelial cells (HBMECs) and observed one or two distinct egress zones per cell at the basal surface. Transmission electron microscopy and 3D electron tomography (ET) of the egress zones revealed clusters of virions within membrane-bound structures, which we term membranous carriers (MCs), approaching and fusing with the plasma membrane. These virion-containing MCs emerged from larger, LAMP-1-positive membranous organelles that are morphologically compatible with lysosomes. We call these structures sorting organelles (50s). Reovirus infection induces an increase in the number and size of lysosomes and modifies the pH of these organelles from similar to 4.5-5 to similar to 6.1 after recruitment to Vls and before incorporation of virions. ET of VI-50-MC interfaces demonstrated that these compartments are connected by membrane-fusion points, through which mature virions are transported. Collectively, our results show that reovirus uses a previously undescribed, membrane-engaged, nonlytic egress mechanism and highlights a potential new target for therapeutic intervention.

Keywords

Bluetongue virusCell entryCholesterol transportMembranePersistent infectionsPhProteinTraffickingViral replicationVirus replication complexes

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Cell Biology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 28/195, thus managing to position itself as a Q1 (Primer Cuartil), in the category Cell Biology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations from Scopus Elsevier, it yields a value for the Field-Weighted Citation Impact from the Scopus agency: 1, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Field Citation Ratio (FCR) from Dimensions: 3.84 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-11, the following number of citations:

  • WoS: 15
  • Scopus: 28
  • OpenCitations: 27

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-11:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 39.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 38 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 114.15.
  • The number of mentions on the social network Facebook: 4 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 25 (Altmetric).
  • The number of mentions in news outlets: 14 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United States of America.