Imaging analysis reveals budding of filamentous human metapneumovirus virions and direct transfer of inclusion bodies through intercellular extensions

dc.creatorNajjar, Farah El
dc.creatorCastillo, Santiago Restrepo
dc.creatorMoncman, Carole L.
dc.creatorWu, Cheng-Yu
dc.creatorIsla, Eduardo
dc.creatorVelez Ortega, A. Catalina
dc.creatorFrolenkov, Gregory I.
dc.creatorCifuentes-Munoz, Nicolas
dc.creatorDutch, Rebecca Ellis
dc.date2024-04-10T02:00:15Z
dc.date2024-04-10T02:00:15Z
dc.date2023
dc.date.accessioned2024-07-17T21:13:26Z
dc.date.available2024-07-17T21:13:26Z
dc.identifier10.1128/mbio.01589-23
dc.identifier21612129
dc.identifierhttps://hdl.handle.net/20.500.12728/10738
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9509506
dc.descriptionHuman metapneumovirus (HMPV) can spread between cells through budding of virus particles or direct cell-to-cell spread. A network of budding filaments and intercellular extensions forms in HMPV-infected cells; however, the involvement of these structures in direct cell-to-cell spread of infection remains to be investigated. Utilizing advanced imaging techniques, we show that budding filaments contain the viral RNA genome, and not the antigenome, and become enriched with HMPV F protein as infection progresses. Multiple filaments containing the F protein on their surface were seen emanating from one cell to contact a neighboring cell, strongly suggesting that these are budding filamentous HMPV virions. In addition, changes in the morphology and properties of intercellular extensions following HMPV infection were detected. We show that intercellular extensions allow the transfer of a cytosolic dye only in HMPV-infected cells. In addition, using live imaging, we provide novel evidence of the direct passage of inclusion bodies from cell-to-cell across intercellular extensions. These results provide novel insights into the direct cell-to-cell spread of HMPV and suggest that this mode of transmission can occur through different mechanisms. IMPORTANCE Human metapneumovirus is an important respiratory pathogen that causes significant morbidity and mortality, particularly in the very young, the elderly, and the immunosuppressed. However, the molecular details of how this virus spreads to new target cells are unclear. This work provides important new information on the formation of filamentous structures that are consistent with virus particles and adds critical new insight into the structure of extensions between cells that form during infection. In addition, it demonstrates for the first time the movement of viral replication centers through these intercellular extensions, representing a new mode of direct cell-to-cell spread that may be applicable to other viral systems. Copyright © 2023 El Najjar et al.
dc.descriptionNational Institutes of Health, NIH; National Institute of Allergy and Infectious Diseases, NIAID
dc.formatapplication/pdf
dc.languageen
dc.publisherAmerican Society for Microbiology
dc.subjectHMPV
dc.subjectpneumovirus
dc.subjectrespiratory viruses
dc.subjectviral spread
dc.titleImaging analysis reveals budding of filamentous human metapneumovirus virions and direct transfer of inclusion bodies through intercellular extensions
dc.typeArticle


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