Tunneling nanotubes as a novel route of cell-to-cell spread of herpesviruses

Mirosława Panasiuk , Michał Rychłowski , Natalia Derewońko , Krystyna Bieńkowska-Szewczyk


Various types of intercellular connections that are essential for communication between cells are often utilized by pathogens. Recently, a new type of cellular connection, consisting of long, thin, actin-rich membrane extensions named tunneling nanotubes (TNTs), has been shown to play an important role in cell-to-cell spread of HIV and influenza virus. In the present report, we show that TNTs are frequently formed by cells infected by an alphaherpesvirus, bovine herpesvirus 1 (BoHV-1). Viral proteins, such as envelope glycoprotein E (gE), capsid protein VP26, and tegument protein Us3, as well as cellular organelles (mitochondria) were detected by immunofluorescence and live-cell imaging of nanotubes formed by bovine primary fibroblasts and oropharynx cells (KOP cells). Time-lapse confocal studies of live cells infected with fluorescently labeled viruses showed that viral particles were transmitted via TNTs. This transfer also occurred in the presence of neutralizing antibodies, which prevented free entry of BoHV-1. We conclude that TNT formation contributes to successful cell-to-cell spread of BoHV-1 and demonstrate for the first time the participation of membrane nanotubes in intercellular transfer of a herpesvirus in live cells.IMPORTANCE: Efficient transmission of viral particles between cells is an important factor in successful infection by herpesviruses. Herpesviruses can spread by the free-entry mode or direct cell-to-cell transfer via cell junctions and long extensions of neuronal cells. In this report, we show for the first time that an alphaherpesvirus can also spread between various types of cells using tunneling nanotubes, intercellular connections that are utilized by HIV and other viruses. Live-cell monitoring revealed that viral transmission occurs between the cells of the same type as well as between epithelial cells and fibroblasts. This newly discovered route of herpesviruses spread may contribute to efficient transmission despite the presence of host immune responses, especially after reactivation from latency that developed after primary infection. Long-range communication provided by TNTs may facilitate the spread of herpesviruses between many tissues and organs of an infected organism.
Autor Mirosława Panasiuk (MWB UG i GUMed)
Mirosława Panasiuk
- Międzyuczelniany Wydział Biotechnologii UG i GUMed
, Michał Rychłowski (MWB UG i GUMed / IB UG / ZBMW)
Michał Rychłowski
- Zakład Biologii Molekularnej Wirusów
, Natalia Derewońko (MWB UG i GUMed)
Natalia Derewońko
- Międzyuczelniany Wydział Biotechnologii UG i GUMed
, Krystyna Bieńkowska-Szewczyk (MWB UG i GUMed / IB UG / ZBMW)
Krystyna Bieńkowska-Szewczyk
- Zakład Biologii Molekularnej Wirusów
Tytuł czasopisma/seriiJournal of Virology, ISSN 0022-538X, (A 40 pkt)
Rok wydania2018
Objętość publikacji w arkuszach wydawniczych0.3
Numer artykułue00090-18
Słowa kluczowe w języku angielskimtunneling nanotubes, TNT, herpes, BoHV-1, bovine herpesvirus 1, cell-to-cell transmission
Klasyfikacja ASJC2406 Virology; 1109 Insect Science; 2403 Immunology; 2404 Microbiology
Języken angielski
Punktacja (całkowita)40
Żródło punktacjijournalList
PunktacjaPunktacja MNiSW = 40.0, 17-11-2019, ArticleFromJournal
Wskaźniki publikacji Cytowania WoS = 5; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.047; Impact Factor WoS: 2018 = 4.324 (2) - 2018=4.259 (5)
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