An Human Precision-cut Lung Slice Platform Provides Insight into SARS-CoV-2 Pathogenesis and Antiviral Drug Efficacy

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2024 Jun 28

PMID 38940558

Authors

Roger D Pechous

Priyangi A Malaviarachchi

Srijon K Banerjee

Stephanie D Byrum

Duah H Alkam

Alireza Ghaffarieh

Richard C Kurten

Joshua L Kennedy

Xuming Zhang

Affiliations

Soon will be listed here.

Abstract

Importance: Here, established an human precision-cut lung slice platform for assessing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral replication kinetics, innate immune response, disease progression, and antiviral drugs. Using this platform, we identified early induction of specific cytokines, especially IP-10 and IL-8, as potential predictors for severe coronavirus disease 2019 (COVID-19), and uncovered a hitherto unrecognized phenomenon that while infectious virus disappears at late times of infection, viral RNA persists and lung histopathology commences. This finding may have important clinical implications for both acute and post-acute sequelae of COVID-19. This platform recapitulates some of the characteristics of lung disease observed in severe COVID-19 patients and is therefore a useful platform for understanding mechanisms of SARS-CoV-2 pathogenesis and for evaluating the efficacy of antiviral drugs.

Citing Articles

Differential transcriptomic host responses in the early phase of viral and bacterial infections in human lung tissue explants ex vivo.

Sohail A, Waqas F, Braubach P, Czichon L, Samir M, Iqbal A Respir Res. 2024; 25(1):369.

PMID: 39395995 PMC: 11471021. DOI: 10.1186/s12931-024-02988-8.

SARS-CoV-2 Viral Replication Persists in the Human Lung for Several Weeks after Symptom Onset.

Tomasicchio M, Jaumdally S, Wilson L, Kotze A, Semple L, Meier S Am J Respir Crit Care Med. 2024; 209(7):840-851.

PMID: 38226855 PMC: 10995573. DOI: 10.1164/rccm.202308-1438OC.

References

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z . clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (Camb). 2021; 2(3):100141. PMC: 8454663. DOI: 10.1016/j.xinn.2021.100141. View

Mak I, Evaniew N, Ghert M . Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res. 2014; 6(2):114-8. PMC: 3902221. View

Hou Y, Okuda K, Edwards C, Martinez D, Asakura T, Dinnon 3rd K . SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell. 2020; 182(2):429-446.e14. PMC: 7250779. DOI: 10.1016/j.cell.2020.05.042. View

Lavi E, Gilden D, Highkin M, Weiss S . Persistence of mouse hepatitis virus A59 RNA in a slow virus demyelinating infection in mice as detected by in situ hybridization. J Virol. 1984; 51(2):563-6. PMC: 254475. DOI: 10.1128/JVI.51.2.563-566.1984. View

Griffin I, Woodworth K, Galang R, Burkel V, Neelam V, Siebman S . Recurrent SARS-CoV-2 RNA Detection after COVID-19 Illness Onset during Pregnancy. Emerg Infect Dis. 2022; 28(4):873-876. PMC: 8962892. DOI: 10.3201/eid2804.212354. View

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

Blanco-Melo D, Nilsson-Payant B, Liu W, Uhl S, Hoagland D, Moller R . Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 2020; 181(5):1036-1045.e9. PMC: 7227586. DOI: 10.1016/j.cell.2020.04.026. View

Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Manry J . Autoantibodies neutralizing type I IFNs are present in 4% of uninfected individuals over 70 years old and account for 20% of COVID-19 deaths. Sci Immunol. 2021; 6(62. PMC: 8521484. DOI: 10.1126/sciimmunol.abl4340. View

Childs K, Goodbourn S . Identification of novel co-repressor molecules for Interferon Regulatory Factor-2. Nucleic Acids Res. 2003; 31(12):3016-26. PMC: 162335. DOI: 10.1093/nar/gkg431. View

10.

Cao J, Forrest J, Zhang X . A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs. Antiviral Res. 2014; 114:1-10. PMC: 7113785. DOI: 10.1016/j.antiviral.2014.11.010. View

11.

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

12.

Bradley B, Maioli H, Johnston R, Chaudhry I, Fink S, Xu H . Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series. Lancet. 2020; 396(10247):320-332. PMC: 7365650. DOI: 10.1016/S0140-6736(20)31305-2. View

13.

Caramaschi S, Kapp M, Miller S, Eisenberg R, Johnson J, Epperly G . Histopathological findings and clinicopathologic correlation in COVID-19: a systematic review. Mod Pathol. 2021; 34(9):1614-1633. PMC: 8141548. DOI: 10.1038/s41379-021-00814-w. View

14.

Choy K, Wong A, Kaewpreedee P, Sia S, Chen D, Hui K . Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020; 178:104786. PMC: 7127386. DOI: 10.1016/j.antiviral.2020.104786. View

15.

Henjakovic M, Sewald K, Switalla S, Kaiser D, Muller M, Veres T . Ex vivo testing of immune responses in precision-cut lung slices. Toxicol Appl Pharmacol. 2008; 231(1):68-76. DOI: 10.1016/j.taap.2008.04.003. View

16.

Lal S, Li A, Dos Remedios C . Limitations in Translating Animal Studies to Humans in Cardiovascular Disease. J Cardiovasc Transl Res. 2016; 9(2):165-6. DOI: 10.1007/s12265-016-9676-2. View

17.

Smith N, Posseme C, Bondet V, Sugrue J, Townsend L, Charbit B . Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity. Nat Commun. 2022; 13(1):7254. PMC: 9700809. DOI: 10.1038/s41467-022-34895-1. View

18.

Goedhart J, Luijsterburg M . VolcaNoseR is a web app for creating, exploring, labeling and sharing volcano plots. Sci Rep. 2020; 10(1):20560. PMC: 7689420. DOI: 10.1038/s41598-020-76603-3. View

19.

Stein S, Ramelli S, Grazioli A, Chung J, Singh M, Yinda C . SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature. 2022; 612(7941):758-763. PMC: 9749650. DOI: 10.1038/s41586-022-05542-y. View

20.

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J . A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382(8):727-733. PMC: 7092803. DOI: 10.1056/NEJMoa2001017. View