Kinetics and Immunodominance of Virus-Specific T Cell Responses During Hantaan Virus Infection

Wang, Meiliang; Wang, Jiuping; Kang, Zhenhua; Zhao, Qiuling; Wang, Xiaohui; Ling, Hui

doi:10.1089/vim.2014.0135

Cited by 13 publications

(14 citation statements)

References 17 publications

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“…In a mouse model of persistent infection, almost no IFN-γ-producing T cells were detected, while mice with transient infection showed increased functional HTNV-specific CTLs ( 23 , 47 ). HTNV-specific T-cell responses in patients with severe HFRS were heavily impaired at the early stage of infection, indicating that an initial failure to mount strong T-cell responses may be the primary cause of the progression of acute HTNV infection into severe HFRS ( 27 ). In our study, when remove the ELISPOT data of patients with severe/critical disease, the numbers of epitope VV9-specific CD8 + T cells were significantly larger than that in NC, indicating patients with milder disease may have more functional epitope-specific CD8 + T cells.…”

Section: Discussionmentioning

confidence: 99%

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Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/Kb Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome

et al. 2017

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Hantaan virus (HTNV) infections can cause severe hemorrhagic fever with renal syndrome (HFRS) in humans, which is associated with high fatality rates. Cytotoxic T cell (CTL) responses contribute to virus elimination; however, to date, HLA class I allele-restricted HTNV glycoprotein (GP) epitopes recognized by CTLs have not been reported, limiting our understanding of CTL responses against HTNV infection in humans. In this study, 34 HTNV GP nine-mer epitopes that may bind to HLA-A*0201 molecules were predicted using the BIMAS and SYFPEITHI database. Seven of the epitopes were demonstrated to bind to HLA-A*0201 molecules with high affinity via the T2 cell binding assay and were successfully used to synthesize peptide/HLA-A*0201 tetramers. The results of tetramer staining showed that the frequencies of each epitope-specific CTL were higher in patients with milder HFRS, which indicated that the epitopes may induce protective CTL responses after HTNV infection. IFN-γ-enzyme-linked immunospot analysis further confirmed the immunoreactivity of epitopes by eliciting epitope-specific IFN-γ-producing CTL responses. In an HTNV challenge trial, significant inhibition of HTNV replication characterized by lower levels of antigens and RNA loads was observed in major target organs (liver, spleen, and kidneys) of HLA-A2.1/Kb transgenic mice pre-vaccinated with nonapeptides VV9 (aa8–aa16, VMASLVWPV), SL9 (aa996–aa1004, SLTECPTFL) and LL9 (aa358–aa366, LIWTGMIDL). Importantly, LL9 exhibited the best ability to induce protective CTL responses and showed a prominent effect on the kidneys, potentially preventing kidney injury after HTNV infection. Taken together, our results highlight that HTNV GP-derived HLA-A*0201-restricted epitopes could elicit protective CTL responses against the virus, and that epitope LL9 functions as an immunodominant protective epitope that may advance the design of safe and effective CTL-based HTNV peptide vaccines for humans.

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Section: Discussionmentioning

confidence: 99%

“…To date, most HTNV-specific CTL epitopes identified are distributed on NP ( 6 , 27 , 28 ). Early research identified three CTL epitopes on HTNV NP ( 25 , 29 ).…”

Section: Introductionmentioning

confidence: 99%

Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/Kb Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome

et al. 2017

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“…Clinical remission after severe HFRS is also associated with a sustained IFN-γ/granzyme B CD8 + T-cell response, even in the absence of detectable neutralizing antibodies [139]. In contrast, a low IFN-γ T-cell response is also associated with severe HFRS [140]. Among total T-cells, the CD8 + subset is responsible for the major response to HTNV peptides [45,140].…”

Section: Particular Characteristics Of the T-cell Response Againstmentioning

confidence: 99%

“…In contrast, a low IFN-γ T-cell response is also associated with severe HFRS [140]. Among total T-cells, the CD8 + subset is responsible for the major response to HTNV peptides [45,140]. Indeed, HTNV-specific CD8 + T-cells are required for efficient viral clearance in mice via production of IFN-γ, TNF-α, and cytotoxicity, and their low frequency leads to a persistent infection [141,142], such as seen in the hantavirus reservoir, deer mice [143].…”

Section: Particular Characteristics Of the T-cell Response Againstmentioning

confidence: 99%

T-Cell Response to Viral Hemorrhagic Fevers

et al. 2019

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Viral hemorrhagic fevers (VHF) are a group of clinically similar diseases that can be caused by enveloped RNA viruses primarily from the families Arenaviridae, Filoviridae, Hantaviridae, and Flaviviridae. Clinically, this group of diseases has in common fever, fatigue, dizziness, muscle aches, and other associated symptoms that can progress to vascular leakage, bleeding and multi-organ failure. Most of these viruses are zoonotic causing asymptomatic infections in the primary host, but in human beings, the infection can be lethal. Clinical and experimental evidence suggest that the T-cell response is needed for protection against VHF, but can also cause damage to the host, and play an important role in disease pathogenesis. Here, we present a review of the T-cell immune responses to VHF and insights into the possible ways to improve counter-measures for these viral agents.

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“…However, immunodominant T cell responses are central in the control of any acute virus infection. A study reported weakening of IFN-γ- producing T cell response in patients with severe HFRS at the early stage of infection [ 47 ]. The study suggested that insufficient T cell response to the immunodominant epitopes might play a role in influencing the severity of HTNV infection.…”

Section: Discussionmentioning

confidence: 99%

Short peptide epitope design from hantaviruses causing HFRS

et al. 2017

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Several genotypes of the hantavirus cause hemorrhagic fever with renal syndrome (HFRS) and is an important public health problem worldwide. There is now growing interest to develop subunit vaccines especially focused to elicit cytotoxic T lymphocyte responses which are important against viral infection. We identified candidate T-cell epitopes that bind to Class I HLA supertypes towards identifying potential subunit vaccine entity. These epitopes are conserved in all 5 hantavirus genotypes of HFRS (Hantaan, Dobrava- Belgrade, Seoul, Gou virus and Amur). The epitopes identified from S and M segment genomes were analyzed for human proteasome cleavage, transporter associated antigen processing (TAP) efficiency and antigenicity using bioinformatic approaches. The epitope MRNTIMASK which had the two characteristics of high proteasomal cleavage score and TAP score, also had high antigenicity score. Our results indicate that this epitope from the nucleocapsid protein may be considered the most favorable moiety for the development of subunit peptide vaccine.

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Kinetics and Immunodominance of Virus-Specific T Cell Responses During Hantaan Virus Infection

Cited by 13 publications

References 17 publications

Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/Kb Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome

Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/Kb Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome

T-Cell Response to Viral Hemorrhagic Fevers

Short peptide epitope design from hantaviruses causing HFRS

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