Measles Virus Preferentially Transduces the Basolateral Surface of Well-Differentiated Human Airway Epithelia

Abstract

Measles virus (MV) is typically spread by aerosol droplets and enters via the respiratory tract. The progression of MV infection has been widely studied; yet, the pathway for virus entry in polarized human airway epithelia has not been investigated. Herein we report the use of a replication-competent Edmonston vaccine strain of MV expressing enhanced green fluorescent protein (MV-eGFP) to infect primary cultures of well-differentiated human airway epithelia. Previous studies with polarized Caco-2 cells (intestine-derived human epithelia) and MDCK cells (kidney-derived canine epithelia) demonstrated that MV primarily infected and exited the apical surface. In striking contrast, our results indicate that MV preferentially transduces human airway cells from the basolateral surface; however, virus release remains in an apical direction. When MV-eGFP was applied apically or basolaterally to primary cultures of airway epithelia, discrete foci of eGFP expression appeared and grew; however, the cell layer integrity was maintained for the duration of the study (7 days). Interestingly, utilizing immunohistochemistry and confocal microscopy, we observed widespread expression of the receptor for the vaccine strain of MV (CD46) at greatest abundance on the apical surface of the differentiated human airway epithelia as well as in human tracheal tissue sections. These data suggest that the progression of MV infection through the respiratory epithelium may involve pathways other than direct binding and entry through the apical surface of airway epithelia.

Tropism illuminated: Lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system

“…Lymphocytes disseminate infection in the organism; in particular, epithelia are infiltrated by lymphocytes that occasionally may succumb to the infection load and locally release virus. Lung epithelium infection may be initiated from the basal side, consistent with the observation that MV preferentially transduces the basolateral surface of welldifferentiated human airway epithelia (31). This sequence of events is different from previous morbillivirus infection models: based on limited evidence, it was assumed that the initial MV infection is established in the respiratory tract (2,3).…”

Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus

“…It remains to be determined if such variation is linked to either differences in the extent of epithelial disruption or the virus burden in the epithelium of the URT. Although in vitro studies have shown that epithelial cells can be infected by MV and produce new virus particles by budding from the apical membrane (Sinn et al, 2002;Tahara et al, 2008;Takeuchi et al, 2003), MV cell-to-cell spread is relatively slow and results in the release of low virus titres (Leonard et al, 2008;Ludlow et al, 2010;Mühlebach et al, 2011). In contrast, the MV replication cycle in lymphocytes is usually more rapid and results in higher levels of viral shedding (de Vries et al, 2010a;Lemon et al, 2011).…”

Adenovirus serotype 35 vector-mediated transduction into human CD46-transgenic mice

“…Human CD46 primarily is expressed on the basolateral surfaces of polarized epithelial cells, 42,43 and measles virus preferentially infects cells from their basolateral, rather than apical, sides. 44 Anatomical barriers such as the tightness between the basal membrane and extracellular matrix might impair the access of Ad35 vectors to the human CD46 on the basolateral cell surface. Another possibility is that an unidentified receptor or co-receptor for Ad35 is expressed in humans but not in CD46TG mice.…”