Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection

Channappanavar, Rudragouda; Fett, Craig; Zhao, Jincun; Meyerholz, David K.; Perlman, Stanley

doi:10.1128/jvi.01505-14

Cited by 430 publications

(457 citation statements)

References 51 publications

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“…Following RSV challenge, DC-LM-immunized mice exhibited significantly enhanced weight loss, pulmonary dysfunction, and mortality compared to controls. These results were unexpected given that similar immunization approaches to generate high magnitude memory CD8 T cell responses to other respiratory viruses, including influenza virus and SARS coronavirus, did not result in immunopathology following viral challenge [70,71]. Interestingly, the induction of immunopathology mediated by both primary and memory CD8 T cells is largely driven by cytokine production, particularly IFN-γ and TNF, as will be discussed in detail in Sections 3.2 and 3.3 below [12,14].…”

Section: Cd8 T Cell-mediated Immunopathologymentioning

confidence: 97%

Cytokines and CD8 T cell immunity during respiratory syncytial virus infection

Schmidt

Varga

2020

Cytokine

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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection and hospitalization in infants. In spite of the enormous clinical burden caused by RSV infections, there remains no efficacious RSV vaccine. CD8 T cells mediate viral clearance as well as provide protection against a secondary RSV infection. However, RSV-specific CD8 T cells may also induce immunopathology leading to exacerbated morbidity and mortality. Many of the crucial functions performed by CD8 T cells are mediated by the cytokines they produce. IFN-γ and TNF are produced by CD8 T cells following RSV infection and contribute to both the acceleration of viral clearance and the induction of immunopathology. To prevent immunopathology, regulatory mechanisms are in place within the immune system to inhibit CD8 T cell effector functions after the infection has been cleared. The actions of a variety of cytokines, including IL-10 and IL-4, play a critical role in the regulation of CD8 T cell effector activity. Herein, we review the current literature on CD8 T cell responses and the functions of the cytokines they produce following RSV infection. Additionally, we discuss the regulation of CD8 T cell activation and effector functions through the actions of various cytokines.

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Section: Cd8 T Cell-mediated Immunopathologymentioning

confidence: 97%

Cytokines and CD8 T cell immunity during respiratory syncytial virus infection

Schmidt

Varga

2020

Cytokine

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“…However, CD4+ T cells are more susceptible to MERS‐CoV infection. The depletion of CD8+ T cells do not affect and delay viral replication at the time of infection with SARS‐CoV 77,78 . Depletion of CD4+ T cells is associated with reduced pulmonary recruitment of lymphocytes and neutralizing antibody and cytokine production, resulting in a strong immune‐mediated interstitial pneumonitis and delayed clearance of SARS‐CoV from lungs 79 .…”

Section: Adaptive Immune Responsesmentioning

confidence: 99%

Coronavirus infections and immune responses

Fan

Lai

et al. 2020

Journal of Medical Virology

1,665

1,776

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Coronaviruses (CoVs) are by far the largest group of known positive-sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV-induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.

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“…In contrast, virus-specific memory CD8 + T cells persisted for up to 6 years after SARS-CoV infection, at which time memory B cells and virus-specific antibodies were undetectable (Yang et al, 2006). It has been shown that memory CD8 + T cells specific for an immunodominant epitope substantially protected aged mice from lethal SARS-CoV infection (Channappanavar et al, 2014). After challenge, memory CD8 + T cells produced effector cytokines (interferon gamma, IFN-γ; tumor necrosis factor alpha, TNF-α; and interleukin 2, IL-2) and cytolytic molecules, reducing viral loads in the lung.…”

Section: Requirement Of B-and T-cell Responses For Protectionmentioning

confidence: 99%

Molecular Basis of Coronavirus Virulence and Vaccine Development

Enjuanes

Zúñiga

Castaño-Rodríguez

et al. 2016

Advances in Virus Research

147

141

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Virus vaccines have to be immunogenic, sufficiently stable, safe, and suitable to induce long-lasting immunity. To meet these requirements, vaccine studies need to provide a comprehensive understanding of (i) the protective roles of antiviral B and T-cell-mediated immune responses, (ii) the complexity and plasticity of major viral antigens, and (iii) virus molecular biology and pathogenesis. There are many types of vaccines including subunit vaccines, whole-inactivated virus, vectored, and live-attenuated virus vaccines, each of which featuring specific advantages and limitations. While nonliving virus vaccines have clear advantages in being safe and stable, they may cause side effects and be less efficacious compared to live-attenuated virus vaccines. In most cases, the latter induce long-lasting immunity but they may require special safety measures to prevent reversion to highly virulent viruses following vaccination. The chapter summarizes the recent progress in the development of coronavirus (CoV) vaccines, focusing on two zoonotic CoVs, the severe acute respiratory syndrome CoV (SARS-CoV), and the Middle East respiratory syndrome CoV, both of which cause deadly disease and epidemics in humans. The development of attenuated virus vaccines to combat infections caused by highly pathogenic CoVs was largely based on the identification and characterization of viral virulence proteins that, for example, interfere with the innate and adaptive immune response or are involved in interactions with specific cell types, such as macrophages, dendritic and epithelial cells, and T lymphocytes, thereby modulating antiviral host responses and viral pathogenesis and potentially resulting in deleterious side effects following vaccination.

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Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection

Cited by 430 publications

References 51 publications

Cytokines and CD8 T cell immunity during respiratory syncytial virus infection

Cytokines and CD8 T cell immunity during respiratory syncytial virus infection

Coronavirus infections and immune responses

Molecular Basis of Coronavirus Virulence and Vaccine Development

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