Wild-Type Human Adenovirus (Serotype 41)

Human adenovirus type 41 (HAdV-41) causes acute gastroenteritis in young children. The main symptoms of HAdV-41 infection are diarrhea and vomiting. Here, researchers used the human midgut carcinoid cell line GOT1 to investigate the effects of HAdV-41 infection and its capsid protein on enterochromaffin cell serotonin release and enteric glial cell (EGC) activation. This study established for the first time that HAdV-41 is able to infect enterochromaffin cells. Immunofluorescence staining showed that these cells expressed HAdV-41-specific coxsackievirus and adenovirus receptors (CARs); flow cytometric analysis also supported these findings. HAdV-41 infection of enterochromaffin cells induced serotonin secretion in a dose-dependent manner. In contrast, control HAdV-5 infection did not induce cellular serotonin secretion. Confocal microscopy studies showed that serotonin immunofluorescence in enterochromaffin cells infected with HAdV-41 was reduced compared with that in uninfected cells. Incubation of enterochromaffin cells with purified HAdV-41 short fiber knobs and hexon proteins significantly increased serotonin levels in the cell supernatant. HAdV-41 infection also activated EGCs, as shown by the significant changes in the expression of glial fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. EGCs can also be activated by serotonin alone, as shown by the significant increase in GFAP staining intensity. Similarly, cell supernatants of enterochromaffin cells infected with HAdV-41 also activated EGCs.

Here, researchers infected EC cells with HAdV-41 and studied serotonin secretion by confocal microscopy at 18 h post-infection. The fluorescence intensity of serotonin was altered in EC cells infected with HAdV-41 (n = 30 cells) compared to uninfected cells (n = 30 cells) (Figure 1A). There was a significant linear negative correlation between serotonin intensity between uninfected and infected cells (Figure 1B), with HAdV-41-infected cells showing weaker serotonin immunofluorescence intensity. Therefore, HAdV-41-infected EC cells had weaker serotonin immunofluorescence intensity. Next, the granularity of serotonin-labeled immunofluorescence was analyzed, and the results showed that the serotonin-labeled immunofluorescence intensity was higher and more granular than that of uninfected EC cells. Compared with uninfected cells (n = 30 cells), the serotonin granularity of EC cells infected with HAdV-41 showed a significant positive linear correlation with the serotonin granularity (Figure 1C). Trypan blue staining showed that cell viability was not affected in infected cell cultures (89% live in infected cell cultures versus 82% in mock-treated cultures), nor was any obvious cytopathic effect (CPE) observed, supporting the observation that HAdV-41 undergoes abortive infection in EC cells.

Figure 1. HAdV-41 affects serotonin distribution in human EC cells. (Westerberg S, et al., 2018)