Polar release of pathogenic Old World hantaviruses from renal tubular epithelial cells

Abstract

BackgroundEpithelio- and endotheliotropic viruses often exert polarized entry and release that may be responsible for viral spread and dissemination. Hantaviruses, mostly rodent-borne members of the Bunyaviridae family infect epithelial and endothelial cells of different organs leading to organ dysfunction or even failure. Endothelial and renal epithelial cells belong to the target cells of Old World hantavirus. Therefore, we examined the release of hantaviruses in several renal epithelial cell culture models. We used Vero cells that are commonly used in hantavirus studies and primary human renal epithelial cells (HREpC). In addition, we analyzed MDCKII cells, an epithelial cell line of a dog kidney, which represents a widely accepted in vitro model of polarized monolayers for their permissiveness for hantavirus infection.ResultsVero C1008 and primary HREpCs were grown on porous-support filter inserts for polarization. Monolayers were infected with hantavirus Hantaan (HTNV) and Puumala (PUUV) virus. Supernatants from the apical and basolateral chamber of infected cells were analyzed for the presence of infectious particles by re-infection of Vero cells. Viral antigen and infectious particles of HTNV and PUUV were exclusively detected in supernatants collected from the apical chamber of infected Vero C1008 cells and HREpCs. MDCKII cells were permissive for hantavirus infection and polarized MDCKII cells released infectious hantaviral particles from the apical surface corresponding to the results of Vero and primary human epithelial cells.ConclusionsPathogenic Old World hantaviruses are released from the apical surface of different polarized renal epithelial cells. We characterized MDCKII cells as a suitable polarized cell culture model for hantavirus infection studies.

Gastrointestinal Tract As Entry Route for Hantavirus Infection

“…Hantaviruses preferentially use different β-integrins and CD55/DAF for cell entry (Gavrilovskaya et al, 1999 ; Krautkrämer and Zeier, 2008 ; Raftery et al, 2014 ). However, the presence of some of the receptor molecules on the basolateral side of the affected tissues requires effective disruption, or at least penetration, of the cell barrier, as shown in vitro for different tissue types (Krautkrämer et al, 2012 ). Interference with cellular barrier function of infected tissues can lead to capillary leakage and is a crucial aspect of hantavirus pathogenesis (Vaheri et al, 2013 ).…”

Coronavirus entry and release in polarized epithelial cells: a review

“…The virus specifically released from the apical surface is targeted to the lumen; hence, the resulting infection is more likely to be restricted to the epithelial surface. In contrast, basolateral release should provide access to the blood and lymph vessels, resulting in a systemic infection [23,46]. Clarification of the different release routines of CoVs may provide important insight into the mechanisms of transmission and pathogenesis and will facilitate the design of effective antiviral strategies to control CoV infection.…”