SARS-CoV-2-Infektion des Verdauungstrakts – Experimentelle Ansätze einer Organoid-basierten in vitro Modellierung

Zusammenfassung

SARS-CoV-2 ist eine neuartige humanpathogene Coronavirus-Variante, deren Prädilektion für den Atemwegstrakt zu einer raschen pandemischen Verbreitung durch viruspartikelhaltige Aerosole geführt hat. Die individuelle Organsuszeptibilität wird maßgeblich durch die Besatzdichte mit dem membranständigen Rezeptormolekül ACE2 bestimmt, das als zentraler Interaktionspartner für das virale Spike-Protein den Adhäsions- und Fusionsprozess vermittelt und somit die Grundvoraussetzung zur Aufnahme des Virusgenoms in die Wirtszelle schafft. Ausgehend von einem umfangreichen Datensatz klinischer Studien und Fallberichte, gilt es mittlerweile als gesichert, dass auch bestimmte Zellpopulationen des Verdauungstrakts sowie des funktionell angegliederten olfaktorisch-gustatorischen Systems über die erforderliche Rezeptorenausstattung verfügen und somit durch SARS-CoV-2 „angreifbar“ sind. Zahlreiche Berichte über gastrointestinale Beschwerden und Laborabnormalitäten sind als Indizien für relevante Organdysfunktionen zu werten und untermauern die klinische Bedeutsamkeit einer Mitbeteiligung des Verdauungstrakts im Rahmen einer SARS-CoV-2-Infektion. Organoide sind dreidimensional wachsende In-vitro-Replikate von Organgeweben und nehmen insbesondere dank der organtypisch komplexen zellulären Zusammensetzung und Imitation der physiologischen Funktionsweise von Primärzellen einen hohen Stellenwert für die infektiologische Grundlagenforschung ein. Diese Übersichtsarbeit befasst sich thematisch mit den pathophysiologischen Aspekten der Infektion verdauungsrelevanter Organe mit SARS-CoV-2 unter besonderer Würdigung existierender organoid- oder primärzellkulturbasierter Infektionsmodelle und der daraus hervorgegangenen Erkenntnisse.

Abstract

SARS-CoV-2 is a novel human pathogenic coronavirus whose predilection for the respiratory tract has given rise to a rapid pandemic spread via airborne particles. Organ-specific susceptibility is substantially determined by the density of cell surface expression of ACE2, which is exploited by viral spike protein as a receptor molecule to mediate adhesion and, thus, to permit internalization of the viral genome into the host cell. Based on an ample data set derived from clinical studies and case reports, evidence suggests that distinct cell populations of the digestive and olfactory-gustatory system are equally equipped with membrane-bound ACE2, rendering them “vulnerable” to SARS-CoV-2. Numerous reports on concomitant gastrointestinal complaints and laboratory abnormalities are thought to reflect a relevant degree of organ dysfunction and underscore the tropism of SARS-CoV-2 for the digestive tract. Organoids are three-dimensional in vitro replicas of organ tissue which, owing to their organotypic complex cellular composition and functional resemblance to primary cells, are particularly appreciated for basic research in the field of infectious diseases. This review specifically addresses the involvement of digestive organs by SARS-CoV-2 and outlines the significant contribution of organoid- and primary-cell culture-based models to gaining a deeper understanding of the underlying pathophysiological processes.

Schlüsselwörter

Organoide - SARS-CoV-2 - Infektionsmodell

Keywords

Organoids - SARS-CoV-2 - infection models

Publication History

Received: 04 March 2021

Accepted after revision: 25 April 2021

Article published online:
26 July 2021

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