Regulation of Gene Expression during Viral Infection – Gerald McInerney Group

Our research concerns the study of the interactions between viruses and their host cells in the early stages of infection. Using Semliki Forest virus as a model, we are exploring the involvement of cellular pathways such as autophagy, stress granules and the type I interferon system in the cellular responses to viral infection.

Research Description

Our research concerns the study of the interactions between viruses and their host cells in the early stages of infection. Using Semliki Forest virus as a model,  we are exploring the involvement of cellular pathways such as autophagy, stress granules and the type I interferon system in the cellular responses to viral infection.

For more info please visit our group website: Alphavirus.org

We gratefully receive financial support for our research from several organizations, including:

• Swedish Research Council (Vetenskapsrådet, VR)
• Cancerfonden 
• European Union’s Horizon 2020 research and innovation program
• Knut och Alice Wallenbergs Stiftelse
• Stiftelsen för Strategiskt Forskning
• Karolinska Institutet (KID medel)
• China Scholarship Council
• SciLifeLab National COVID-19 Research Program
• Stiftelsen Clas Groschinskys Minnesfond
• Svenska Sällskapet för Medicinsk Forskning
• WennerGren Stiftelserna
• KI Development Office

Former group members

PhD students

Ainhoa Moliner Morro, 2022

Ben Götte, 2019

Lifeng Liu, 2019

Marc Panas, 2014

Kai Eng, 2012

Postdocs

PhD Marc Panas 

PhD Leo Hanke

PhD Bastian Thaa

PhD Roberta Biasiotto

PhD Thomas Kuri

Immunological memory of Innate Lymphoid Cells

Our research interests are focused in the study of the biology of memory Group 2 Innate Lymphoid Cells (ILC2s) in type 2 immunity.

Read more on the group web page here

Research focus

ILC2s are innate lymphocytes involved in type 2 immune responses that protect us against parasites and play a role in tissue repair. However, they can also be pathogenic and induce allergic reactions. I previously described that ILC2s can become long-lived memory cells and mount more vigorous type 2 immune responses upon subsequent activation. The antigen non-specific nature of memory ILC2s has led me to hypothesize that these cells could be connecting unrelated allergic reactions as well as mediating allergen-independent exacerbations in allergic diseases.

We are performing an in-depth study of the transcriptome, proteome and epigenome of memory ILC2s in both mouse models of allergy and samples from allergic patients. We aim to understand how these innate lymphocytes contribute to the progression of allergic diseases and ultimately help in the development of novel therapeutic approaches.

More recently, we have become interested in the study of the function of ILC2s in the bone marrow (BM). Classically, ILC2s in the BM were thought to serve as progenitors to give rise to ILC2s that will seed peripheral tissues. However, recent evidence showing a functional role for ILC2s in the BM is raising. We study how ILC2s influence bone marrow healthy and malignant hematopoiesis with a focus on bone marrow fibrosis.

Research Focus

Our group is interested in how T cells develop and differentiate in response to antigens and cytokines. In particular, the group is focused on understanding the role of T cells in allergy and cancer.

Read more at the research group website here

T cells recognise peptide/lipid ligands presented in the context of MHC or MHC-like molecules expressed on antigen presenting cells. In particular, the group has a special focus on CD4 T cells, which when activated differentiate into T helper cells with potent cytokine-secreting function. Over the past three decades, several distinct T helper cell subsets have been described including Th1, Th2, Th17, Treg and others and these all exert quite unique immune modulatory effects. My group has many interests, including:

• Understanding how T helper cells promote health and disease
• Deciphering factors that regulate T helper cell function and differentiation
• Phenotyping T helper cells in lymphoid and non-lymphoid tissues in diseased and healthy contexts
• Probing for other functionalities in the T helper cell spectrum
• Understanding how environmental factors may impact on T helper cell functions

Emerging RNA viruses represent a constant threat to global health and despite recent advances in vaccine technologies, our understanding of basic virological processes and viral pathogenesis remains limited. In our team we therefore strive to gain a better understanding of the processes that underlie viral replication, activation of the immune system and viral pathogenesis in order to develop effective and specific antiviral treatments.

Research Focus

Negative-sense RNA viruses consist of some of the most significant human and veterinary pathogens, such as influenza viruses (e.g. influenza A virus) and haemorrhagic fever viruses (e.g. Ebola virus, Lassa virus, Andes virus). These viruses carry highly conserved RNA-dependent RNA polymerases (RdRp) that they use to copy and transcribe their genomes. The process of viral genome replication results in the production of pathogen-associated molecular patterns (PAMPs) that can be sensed by the infected host cell, leading to the induction of pro-inflammatory cytokine signalling, including type I and II interferon (IFN-I/III) and the activation of antiviral interferon stimulated genes (ISGs). Since the RdRp is inherently error-prone, all RNA viruses produce aberrant replication products, so-called defective or non-standard viral genomes.

Our lab’s main goal is to understand the underlying viral and host mechanisms of rodent-borne emerging RNA virus (e.g. hantaviruses and arenaviruses) replication and how to leverage these findings for antiviral treatment and diagnostics.  In particular, we focus on the following questions:

1. How do segmented negative-sense RNA viruses (e.g. hantaviruses) replicate their genomes?
2. How do (alternative) replication products contribute to the viral life cycle and viral pathogenesis?
3. What role does host adaptation play in viral transmission and pathogenesis? 

Selected publications

Amplification-free Detection of Zoonotic Viruses Using Cas13 and Multiple CRISPR RNAs.
Lamb CH, Te Velthuis AJW, Myhrvold C, Nilsson-Payant BE
bioRxiv 2025 May;():

Structural characterization of the full-length Hantaan virus polymerase.
Keown JR, Carrique L, Nilsson-Payant BE, Fodor E, Grimes JM
PLoS Pathog 2024 Dec;20(12):e1012781

A multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection.
Tang X, Xue D, Zhang T, Nilsson-Payant BE, Carrau L, Duan X, Gordillo M, Tan AY, Qiu Y, Xiang J, Schwartz RE, tenOever BR, Evans T, Chen S
Nat Cell Biol 2023 Mar;25(3):381-389

The Host Factor ANP32A Is Required for Influenza A Virus vRNA and cRNA Synthesis.
Nilsson-Payant BE, tenOever BR, Te Velthuis AJW
J Virol 2022 Feb;96(4):e0209221

Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution.
Bose KS, Sarma RH
Biochem Biophys Res Commun 1975 Oct;66(4):1173-9

Reduced Nucleoprotein Availability Impairs Negative-Sense RNA Virus Replication and Promotes Host Recognition.
Nilsson-Payant BE, Blanco-Melo D, Uhl S, Escudero-Pérez B, Olschewski S, Thibault P, Panis M, Rosenthal M, Muñoz-Fontela C, Lee B, tenOever BR
J Virol 2021 Apr;95(9):

Identification of SARS-CoV-2 inhibitors using lung and colonic organoids.
Han Y, Duan X, Yang L, Nilsson-Payant BE, Wang P, Duan F, Tang X, Yaron TM, Zhang T, Uhl S, Bram Y, Richardson C, Zhu J, Zhao Z, Redmond D, Houghton S, Nguyen DT, Xu D, Wang X, Jessurun J, Borczuk A, Huang Y, Johnson JL, Liu Y, Xiang J, Wang H, Cantley LC, tenOever BR, Ho DD, Pan FC, Evans T, Chen HJ, Schwartz RE, Chen S
Nature 2021 Jan;589(7841):270-275

A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids.
Yang L, Han Y, Nilsson-Payant BE, Gupta V, Wang P, Duan X, Tang X, Zhu J, Zhao Z, Jaffré F, Zhang T, Kim TW, Harschnitz O, Redmond D, Houghton S, Liu C, Naji A, Ciceri G, Guttikonda S, Bram Y, Nguyen DT, Cioffi M, Chandar V, Hoagland DA, Huang Y, Xiang J, Wang H, Lyden D, Borczuk A, Chen HJ, Studer L, Pan FC, Ho DD, tenOever BR, Evans T, Schwartz RE, Chen S
Cell Stem Cell 2020 Jul;27(1):125-136.e7

Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19.
Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, Jordan TX, Oishi K, Panis M, Sachs D, Wang TT, Schwartz RE, Lim JK, Albrecht RA, tenOever BR
Cell 2020 May;181(5):1036-1045.e9

The Surface-Exposed PA51-72-Loop of the Influenza A Virus Polymerase Is Required for Viral Genome Replication.
Nilsson-Payant BE, Sharps J, Hengrung N, Fodor E
J Virol 2018 Aug;92(16):

Role of the PB2 627 Domain in Influenza A Virus Polymerase Function.
Nilsson BE, Te Velthuis AJW, Fodor E
J Virol 2017 Apr;91(7):

Team