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Viruses
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T Cell-Mediated Antiviral Immunity
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T Cell-Mediated Antiviral Immunity

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 28069

Special Issue Editor

Dr. Mehul Suthar

E-Mail Website
Guest Editor
Department of Pediatrics, Emory School of Medicine, Atlanta, GA 30322, USA
Interests: flavivirus biology and pathogenesis; innate immune signaling; T cell immunity to virus infection and placental biology

Special Issue Information

Dear Colleagues,

Pattern recognition receptor signalling (TLRs, RLRs, CLRs, and NLRs) can recognize viral pathogen associated molecular patterns and can trigger a robust type-I interferon (IFN) and pro-inflammatory cytokine response that functions to control virus replication and limit spread within a host. Antigen presenting cells (e.g., dendritic cells) provide a critical link between these innate immune signals and priming T-cell responses that function to clear virus infection and provide protection against re-infection. Over the past 20 years, there have been tremendous research efforts to understand the underlying mechanisms that regulate both dendritic cell responses and the development of effector and memory antiviral T-cell responses during virus infection. These efforts have culminated in identifying key transcription factors, signaling components, and cytokines that ultimately determine T-cell fate and function. Recent technological advances and the use of integrated multi-omics-based approaches (e.g., epigenomic, transcriptomic, proteomic, metabolomic, and lipidomic) are providing an unprecedented and global assessment of T-cell responses during virus infection.  In this Special Issue, we will focus on the recent discoveries related to the mechanisms and pathways that determine T-cell fate and function, control T-cell exhaustion, promote tissue-resident memory T-cell responses, and promote viral clearance during virus infection. We will also highlight recent efforts to develop effective T cell-inducing vaccines against viral diseases.

Dr. Mehul Suthar
Guest Editor

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Keywords

  • metabolism
  • tissue-resident memory T cells
  • viral immunology
  • intravital microscopy
  • emgering viruses
  • vaccine-induced T cell immunity
  • regulatory T cells
  • CD4+ T cells
  • CD8+ T cells
  • immunopathology

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Published Papers (5 papers)

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Research

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15 pages, 7297 KiB  
Article
Systematic Identification of Host Immune Key Factors Influencing Viral Infection in PBL of ALV-J Infected SPF Chicken
by Manman Dai, Shibing Li, Keyi Shi, Jiayu Liao, Hui Sun and Ming Liao
Viruses 2020, 12(1), 114; https://doi.org/10.3390/v12010114 - 16 Jan 2020
Cited by 25 | Viewed by 4063
Abstract
Although research related to avian leukosis virus subgroup J (ALV-J) has lasted for more than a century, the systematic identification of host immune key factors against ALV-J infection has not been reported. In this study, we establish an infection model in which four-week-old [...] Read more.
Although research related to avian leukosis virus subgroup J (ALV-J) has lasted for more than a century, the systematic identification of host immune key factors against ALV-J infection has not been reported. In this study, we establish an infection model in which four-week-old SPF chickens are infected with ALV-J strain CHN06, after which the host immune response is detected. We found that the expression of two antiviral interferon-stimulated genes (ISGs) (Mx1 and IFIT5) were increased in ALV-J infected peripheral blood lymphocytes (PBL). A significant CD8+ T cell response induced by ALV-J appeared as early as seven days post-infection (DPI), and humoral immunity starting from 21 DPI differed greatly in the time scale of induction level. Meanwhile, the ALV-J viremia was significantly decreased before antibody production at 14 DPI, and eliminated at 21 DPI under a very low antibody level. The up-regulated CD8+ T cell in the thymus (14DPI) and PBL (7 DPI and 21 DPI) was detected, indicating that the thymus may provide the output of CD8+ T cell to PBL, which was related to virus clearance. Besides, up-regulated chemokine CXCLi1 at 7 DPI in PBL was observed, which may be related to the migration of the CD8+ T cell from the thymus to PBL. More importantly, the CD8 high+ T cell response of the CD8αβ phenotype may produce granzyme K, NK lysin, or IFN-γ for clearing viruses. These findings provide novel insights and direction for developing effective ALV-J vaccines. Full article
(This article belongs to the Special Issue T Cell-Mediated Antiviral Immunity)
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25 pages, 3900 KiB  
Article
Interferon-Gamma Modulation of the Local T Cell Response to Alphavirus Encephalomyelitis
by Victoria K. Baxter and Diane E. Griffin
Viruses 2020, 12(1), 113; https://doi.org/10.3390/v12010113 - 16 Jan 2020
Cited by 22 | Viewed by 5797
Abstract
Infection of mice with Sindbis virus (SINV) provides a model for examining the role of the immune response to alphavirus infection of the central nervous system (CNS). Interferon-gamma (IFN-γ) is an important component of this response, and we show that SINV-infected differentiated neurons [...] Read more.
Infection of mice with Sindbis virus (SINV) provides a model for examining the role of the immune response to alphavirus infection of the central nervous system (CNS). Interferon-gamma (IFN-γ) is an important component of this response, and we show that SINV-infected differentiated neurons respond to IFN-γ in vitro by induction of antiviral genes and suppression of virus replication. To determine the in vivo effects of IFN-γ on SINV clearance and T cell responses, C57BL/6 mice lacking IFN-γ or IFN-γ receptor-1 were compared to wild-type (WT) mice after intracranial SINV infection. In WT mice, IFN-γ was first produced in the CNS by natural killer cells and then by CD4+ and CD8+ T cells. Mice with impaired IFN-γ signaling initiated clearance of viral RNA earlier than WT mice associated with CNS entry of more granzyme B-producing CD8+ T cells. However, these mice established fewer CD8+ tissue-resident memory T (TRM) cells and were more likely to experience reactivation of viral RNA synthesis late after infection. Therefore, IFN-γ suppresses the local development of granzyme B-expressing CD8+ T cells and slows viral RNA clearance but promotes CD8+ TRM cell establishment. Full article
(This article belongs to the Special Issue T Cell-Mediated Antiviral Immunity)
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11 pages, 1398 KiB  
Article
Plasmacytoid Dendritic Cells Contribute to the Production of IFN-β via TLR7-MyD88-Dependent Pathway and CTL Priming during Respiratory Syncytial Virus Infection
by Tae Hoon Kim, Dong Sun Oh, Hi Eun Jung, Jun Chang and Heung Kyu Lee
Viruses 2019, 11(8), 730; https://doi.org/10.3390/v11080730 - 8 Aug 2019
Cited by 23 | Viewed by 3982
Abstract
Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children, yet little is known about the antiviral response of plasmacytoid dendritic cells (pDCs) to RSV infection. We tracked the cellular source of interferon-β using interferon-β/yellow fluorescent protein [...] Read more.
Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children, yet little is known about the antiviral response of plasmacytoid dendritic cells (pDCs) to RSV infection. We tracked the cellular source of interferon-β using interferon-β/yellow fluorescent protein (YFP) reporter mice and identified the signaling pathway activated by RSV that induces type I interferon production in pDCs and DCs. Results from in vitro analyses of RSV-stimulated bone marrow cells revealed that RSV induces interferon-β production in both pDCs and DCs. Kinetic analyses of interferon-β-producing cells in RSV-infected lung cells in vivo indicated that pDCs are rapidly recruited to sites of inflammation during infection. These cells produced interferon-β via the TLR7-MyD88-mediated pathway and IFNα1R-mediated pathway rather than the MAVS-mediated pathway. Moreover, pDC-ablated mice exhibited decreased interferon-γ production and the antigen specificity of CD8+ T cells. Collectively, these data indicate that pDCs play pivotal roles in cytotoxic T lymphocyte (CTL) responses and are one of producers of type I interferon during RSV infection. Full article
(This article belongs to the Special Issue T Cell-Mediated Antiviral Immunity)
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Review

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15 pages, 872 KiB  
Review
To Go or Stay: The Development, Benefit, and Detriment of Tissue-Resident Memory CD8 T Cells during Central Nervous System Viral Infections
by Taryn E. Mockus, Heather M. Ren, Shwetank and Aron E. Lukacher
Viruses 2019, 11(9), 842; https://doi.org/10.3390/v11090842 - 11 Sep 2019
Cited by 9 | Viewed by 6266
Abstract
CD8 T cells coordinate immune defenses against viral infections of the central nervous system (CNS). Virus-specific CD8 T cells infiltrate the CNS and differentiate into brain-resident memory CD8 T cells (CD8 bTRM). CD8 bTRM are characterized by a lack of [...] Read more.
CD8 T cells coordinate immune defenses against viral infections of the central nervous system (CNS). Virus-specific CD8 T cells infiltrate the CNS and differentiate into brain-resident memory CD8 T cells (CD8 bTRM). CD8 bTRM are characterized by a lack of recirculation and expression of phenotypes and transcriptomes distinct from other CD8 T cell memory subsets. CD8 bTRM have been shown to provide durable, autonomous protection against viral reinfection and the resurgence of latent viral infections. CD8 T cells have also been implicated in the development of neural damage following viral infection, which demonstrates that the infiltration of CD8 T cells into the brain can also be pathogenic. In this review, we will explore the residency and maintenance requirements for CD8 bTRM and discuss their roles in controlling viral infections of the brain. Full article
(This article belongs to the Special Issue T Cell-Mediated Antiviral Immunity)
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19 pages, 698 KiB  
Review
Insights into Thymus Development and Viral Thymic Infections
by Francesco Albano, Eleonora Vecchio, Maurizio Renna, Enrico Iaccino, Selena Mimmi, Carmen Caiazza, Alessandro Arcucci, Angelica Avagliano, Valentina Pagliara, Giuseppe Donato, Camillo Palmieri, Massimo Mallardo, Ileana Quinto and Giuseppe Fiume
Viruses 2019, 11(9), 836; https://doi.org/10.3390/v11090836 - 9 Sep 2019
Cited by 17 | Viewed by 7315
Abstract
T-cell development in the thymus is a complex and highly regulated process, involving a wide variety of cells and molecules which orchestrate thymocyte maturation into either CD4+ or CD8+ single-positive (SP) T cells. Here, we briefly review the process regulating T-cell [...] Read more.
T-cell development in the thymus is a complex and highly regulated process, involving a wide variety of cells and molecules which orchestrate thymocyte maturation into either CD4+ or CD8+ single-positive (SP) T cells. Here, we briefly review the process regulating T-cell differentiation, which includes the latest advances in this field. In particular, we highlight how, starting from a pool of hematopoietic stem cells in the bone marrow, the sequential action of transcriptional factors and cytokines dictates the proliferation, restriction of lineage potential, T-cell antigen receptors (TCR) gene rearrangements, and selection events on the T-cell progenitors, ultimately leading to the generation of mature T cells. Moreover, this review discusses paradigmatic examples of viral infections affecting the thymus that, by inducing functional changes within this lymphoid gland, consequently influence the behavior of peripheral mature T-lymphocytes. Full article
(This article belongs to the Special Issue T Cell-Mediated Antiviral Immunity)
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