Zinc Finger CCCH-Type Antiviral Protein 1 Restricts the Viral Replication by Positively Regulating Type I Interferon Response
FRONTIERS IN MICROBIOLOGY
Authors: Zhang, Baoge; Goraya, Mohsan Ullah; Chen, Na; Xu, Lifeng; Hong, Yan; Zhu, Meiyi; Chen, Ji-Long
Abstract
Zinc finger CCCH-type antiviral protein 1 (ZC3HAV1) is a host antiviral factor that can repress translation and promote degradation of specific viral mRNAs. In this study, we found that expression of ZC3HAV1 was significantly induced by infection with influenza A virus (IAV) and Sendai virus (Sev). It was shown that deficiency of IFNAR resulted in a dramatic decrease in the virus-induced expression of ZC3HAV1. Furthermore, transfection with poly(I:C) and treatment with interferon beta (IFN-beta) induced the ZC3HAV1 expression. Interference with the endogenous expression of ZC3HAV1 enhanced the replication of influenza virus by impairing the production of IFN-beta and MxA, following the infection of influenza virus. In contrast, ectopic expression of ZC3HAV1 significantly restricted the replication of influenza virus by increasing the IFN-beta expression. In addition, ZC3HAV1 also promoted the induction of tumor necrosis factor and interleukin 6. These results suggest that ZC3HAV1 is induced by IFN-beta/IFNAR signaling during IAV and Sev infection and involved in positive regulation of IFN-dependent innate antiviral response.
The Impact of TCR Signal Strength on Resident Memory T Cell Formation during Influenza Virus Infection
JOURNAL OF IMMUNOLOGY
Authors: Fiege, Jessica K.; Stone, Ian A.; Fay, Elizabeth J.; Markman, Matthew W.; Wijeyesinghe, Sathi; Macchietto, Marissa G.; Shen, Steven; Masopust, David; Langlois, Ryan A.
Abstract
Resident memory T cells (T-RM) in the lung are vital for heterologous protection against influenza A virus (IAY). Environmental factors are necessary to establish lung T-RM; however, the role of T cell-intrinsic factors like TCR signal strength have not been elucidated. In this study, we investigated the impact of TCR signal strength on the generation and maintenance of lung T-RM after IAV infection. We inserted high- and low-affinity OT-I epitopes into IAV and infected mice after transfer of OT-I T cells. We uncovered a bias in T-RM formation in the lung elicited by lower affinity TCR stimulation. TCR affinity did not impact the overall phenotype or long-term maintenance of lung T-RM. Overall, these findings demonstrate that T-RM formation is negatively correlated with increased TCR signal strength. Lower affinity cells may have an advantage in forming T-RM to ensure diversity in the Ag-specific repertoire in tissues.
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