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IFN-? exerts opposing effects on T cell responses depending on the chronicity of the virus infection.

ABSTRACT: IFN-? induces an antiviral state in many cell types and may contribute to the overall inflammatory environment after infection. Either of these effects may influence adaptive immune responses, but the role of type 3 IFNs in the development of primary and memory T cell responses to infection has not been evaluated. In this study, we examined T cell responses to acute or persistent lymphocytic choriomeningitis virus infection in IFN-?R1-deficient mice. Following acute infection, we find that IFN-?R1-deficient mice produced normal levels of IFN, robust NK cell responses, but greater than normal CD4+ and CD8+ T cell responses compared with wild type BALB/c mice. There were more T cells that were IL-7R(hi) and, correspondingly, the IFN-?R-deficient mice showed a 2- to 3-fold increase in memory T cell number. The inhibitory effect of IFN-?R expression was independent of direct cytokine signaling into T cells. In contrast with acute infection, the IFN-?R-deficient mice generated markedly diminished T cell responses and had greater weight loss compared with wild type mice when confronted with a highly disseminating variant of lymphocytic choriomeningitis virus. These data indicate that IFN-?R limits T cell responses and memory after transient infection but augments T cell responses during persisting infection. Thus, the immune-regulatory functions for IFN-?R are complex and vary with the overall inflammatory environment.

SUBMITTER: Misumi I

PROVIDER: S-EPMC4157331 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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IFN-λ exerts opposing effects on T cell responses depending on the chronicity of the virus infection.

Misumi Ichiro I Whitmire Jason K JK

Journal of immunology (Baltimore, Md. : 1950) 20140319 8

IFN-λ induces an antiviral state in many cell types and may contribute to the overall inflammatory environment after infection. Either of these effects may influence adaptive immune responses, but the role of type 3 IFNs in the development of primary and memory T cell responses to infection has not been evaluated. In this study, we examined T cell responses to acute or persistent lymphocytic choriomeningitis virus infection in IFN-λR1-deficient mice. Following acute infection, we find that IFN-λ ...[more]

PMID: 24646741

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Project description:Virus and host factors contribute to cell-to-cell variation in viral infections and determine the outcome of the overall infection. However, the extent of the variability at the single-cell level and how it impacts virus-host interactions at a system level are not well understood. To characterize the dynamics of viral transcription and host responses, we used single-cell RNA sequencing to quantify at multiple time points the host and viral transcriptomes of human A549 cells and primary bronchial epithelial cells infected with influenza A virus. We observed substantial variability in viral transcription between cells, including the accumulation of defective viral genomes (DVGs) that impact viral replication. We show (i) a correlation between DVGs and virus-induced variation of the host transcriptional program and (ii) an association between differential inductions of innate immune response genes and attenuated viral transcription in subpopulations of cells. These observations at the single-cell level improve our understanding of the complex virus-host interplay during influenza virus infection.IMPORTANCE Defective influenza virus particles generated during viral replication carry incomplete viral genomes and can interfere with the replication of competent viruses. These defective genomes are thought to modulate the disease severity and pathogenicity of an influenza virus infection. Different defective viral genomes also introduce another source of variation across a heterogeneous cell population. Evaluating the impact of defective virus genomes on host cell responses cannot be fully resolved at the population level, requiring single-cell transcriptional profiling. Here, we characterized virus and host transcriptomes in individual influenza virus-infected cells, including those of defective viruses that arise during influenza A virus infection. We established an association between defective virus transcription and host responses and validated interfering and immunostimulatory functions of identified dominant defective viral genome species in vitro This study demonstrates the intricate effects of defective viral genomes on host transcriptional responses and highlights the importance of capturing host-virus interactions at the single-cell level.

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IFN-? exerts opposing effects on T cell responses depending on the chronicity of the virus infection.

Publications

IFN-λ exerts opposing effects on T cell responses depending on the chronicity of the virus infection.

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