Proteomics

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Transcriptomic and proteomic landscape of SARS-CoV-2 liver tropism


ABSTRACT: Extrapulmonary manifestations of COVID-19 have gained attention, not only due to their links to clinical outcomes, but also due to their potential long-term sequelae1. Recent evidence has shown multi-organ tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including heart, kidney and liver2. Previous studies have shown that close to 20% of hospitalized patients with COVID-19 develop liver injury, showing an association to disease severity3. Here, we identified a high frequency of liver enzyme alterations at admission in COVID-19 patients who required hospitalization. Then, we characterized SARS-CoV-2 liver tropism in autopsy samples, based on the expression of cell-entry facilitators in parenchymal cells, clinical polymerase chain reaction (PCR) positivity, subgenomic SARS-CoV-2 identification using RNA sequencing, and viral RNA detection by in situ hybridization. Next, we unraveled the transcriptomic and proteomic landscape of SARS-CoV-2 liver tropism, revealing significant increases in interferon alpha and gamma signaling and compensatory liver-specific metabolic regulation. While these results reflect changes in tissues from patients with severe SARS-CoV-2 infection, these profound molecular alterations raise questions about the potential long-term consequences of COVID-19 infection.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Pietro Scaturro  

LAB HEAD: Pietro Scaturro

PROVIDER: PXD022789 | Pride | 2022-04-02

REPOSITORIES: Pride

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Publications

Molecular consequences of SARS-CoV-2 liver tropism.

Wanner Nicola N   Andrieux Geoffroy G   Badia-I-Mompel Pau P   Edler Carolin C   Pfefferle Susanne S   Lindenmeyer Maja T MT   Schmidt-Lauber Christian C   Czogalla Jan J   Wong Milagros N MN   Okabayashi Yusuke Y   Braun Fabian F   Lütgehetmann Marc M   Meister Elisabeth E   Lu Shun S   Noriega Maria L M MLM   Günther Thomas T   Grundhoff Adam A   Fischer Nicole N   Bräuninger Hanna H   Lindner Diana D   Westermann Dirk D   Haas Fabian F   Roedl Kevin K   Kluge Stefan S   Addo Marylyn M MM   Huber Samuel S   Lohse Ansgar W AW   Reiser Jochen J   Ondruschka Benjamin B   Sperhake Jan P JP   Saez-Rodriguez Julio J   Boerries Melanie M   Hayek Salim S SS   Aepfelbacher Martin M   Scaturro Pietro P   Puelles Victor G VG   Huber Tobias B TB  

Nature metabolism 20220328 3


Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae<sup>1</sup>. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated<sup>2,3</sup>. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that l  ...[more]

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