Nipah virus replication in respiratory epithelial cells
Research area: Molecular Virology
The Malaysian Nipah virus (NiV) strain, a BSL-4 classified zoonotic paramyxovirus, emerged for the first time in 1998 and caused clinical diseases in pigs, which spread the infection to humans. While pigs developed an acute respiratory disease due to a highly efficient virus replication and associated inflammation processes in the airway epithelium, humans developed severe encephalitis with limited respiratory symptoms and little virus shedding via respiratory secretions. These differences in the clinical symptoms suggest species-specific differences in the infection of respiratory epithelial cells. Aiming to identify relevant host factors, we compared NiV infection in primary airway cultures of both species in terms of virus replication efficiencies and innate immune responses. A major finding was that NiV infections resulted in the expression of type III interferons (IFN-λ) in cells of both species with substantial quantitative differences. IFN induction was much lower in porcine airway cells, indicating an inherently limited IFN response. Surprisingly, the expression of proinflammatory cytokines (IL-6, IL-8) was not decreased in porcine epithelia. To evaluate the model that limited antiviral activity in porcine airway cells in the presence of a functional proinflammatory cytokine response is one of the species-specific factors contributing to the differences in NiV replication and virus-induced inflammatory processes, we will investigate the underlying signaling pathways in porcine and human airway epithelia. Here, we will focus on IFN-dependent and -independent expression of antiviral genes and proinflammatory cytokines in infected and uninfected bystander cells. The second part of the project is based on our recent findings that NiV not only forms cytosolic inclusion bodies (IBs), as is typical for all mononegaviruses, but additionally builds inclusions at the plasma membrane. Since the functional role of the two different types of inclusions in airway epithelia is still unknown, we will investigate their role in triggering or counteracting innate immune responses.
Project-related publications of the investigator:
- Becker N, Heiner A, & Maisner A. 2022. Cytosolic Nipah Virus Inclusion Bodies Recruit Proteins Without Using Canonical Aggresome Pathways. Front. Virol. 1:821004.
- Ringel M, Behner L, Heiner A, Sauerhering L, Maisner A. 2020. Replication of a Nipah Virus Encoding a Nuclear-Retained Matrix Protein. J Infect Dis 221:S389-S394.
- Elvert M, Sauerhering L, Maisner A. 2020. Cytokine Induction in Nipah Virus-Infected Primary Human and Porcine Bronchial Epithelial Cells. J Infect Dis 221:S395-S400.
- Ringel M, Heiner A, Behner L, Halwe S, Sauerhering L, Becker N, Dietzel E, Sawatsky B, Kolesnikova L, Maisner A. 2019. Nipah virus induces two inclusion body populations: Identification of novel inclusions at the plasma membrane. PLoS Pathog 15:e1007733.
- Hoffmann M, Nehlmeier I, Brinkmann C, Krahling V, Behner L, Moldenhauer AS, Kruger N, Nehls J, Schindler M, Hoenen T, Maisner A, Becker S, Pohlmann S. 2019. Tetherin Inhibits Nipah Virus but Not Ebola Virus Replication in Fruit Bat Cells. J Virol 93.
- Behner L, Zimmermann L, Ringel M, Weis M, Maisner A. 2018. Formation of high-order oligomers is required for functional bioactivity of an African bat henipavirus surface glycoprotein. Vet Microbiol 218:90-97.
- Sauerhering L, Muller H, Behner L, Elvert M, Fehling SK, Strecker T, Maisner A. 2017. Variability of interferon-lambda induction and antiviral activity in Nipah virus infected differentiated human bronchial epithelial cells of two human donors. J Gen Virol 98:2447-2453.
- Sauerhering L, Zickler M, Elvert M, Behner L, Matrosovich T, Erbar S, Matrosovich M, Maisner A. 2016. Species-specific and individual differences in Nipah virus replication in porcine and human airway epithelial cells. J Gen Virol 97:1511-1519.