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HTNV infection of CD8⁺ T cells is associated with disease progression in HFRS patients.

ABSTRACT: Hantaan viruses (HTNVs) are zoonotic pathogens transmitted mainly by rodents and capable of infecting humans. Increasing knowledge of the human response to HTNV infection can guide the development of new preventative vaccines and therapeutic strategies. Here, we show that HTNV can infect CD8⁺ T cells in vivo in patients diagnosed with hemorrhagic fever with renal syndrome (HFRS). Electron microscopy-mediated tracking of the life cycle and ultrastructure of HTNV-infected CD8⁺ T cells in vitro showed an association between notable increases in cytoplasmic multivesicular bodies and virus production. Notably, based on a clinical cohort of 280 patients, we found that circulating HTNV-infected CD8⁺ T cell numbers in blood were proportional to disease severity. These results demonstrate that viral infected CD8⁺ T cells may be used as an adjunct marker for monitoring HFRS disease progression and that modulating T cell functions may be explored for new treatment strategies.

SUBMITTER: Liu R

PROVIDER: S-EPMC8173013 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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HTNV infection of CD8+ T cells is associated with disease progression in HFRS patients.

Liu Rongrong R Ma Ruixue R Liu Ziyu Z Hu Haifeng H Shu Jiayi J Hu Peizhen P Kang Junjun J Zhang Yusi Y Han Mingwei M Zhang Xiaoxiao X Zheng Yiting Y Ying Qikang Q Hou Shiyuan S Wang Wenqiu W Wang Fang F Cheng Ning N Zhuang Yan Y Lian Jianqi J Jin Xia X Wu Xingan X

Communications biology 20210602 1

Hantaan viruses (HTNVs) are zoonotic pathogens transmitted mainly by rodents and capable of infecting humans. Increasing knowledge of the human response to HTNV infection can guide the development of new preventative vaccines and therapeutic strategies. Here, we show that HTNV can infect CD8+ T cells in vivo in patients diagnosed with hemorrhagic fever with renal syndrome (HFRS). Electron microscopy-mediated tracking of the life cycle and ultrastructure of HTNV-infected CD8+</sup ...[more]

PMID: 34079056

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Project description:The host immunological response is a key factor determining the pathogenesis of cutaneous leishmaniasis. It is known that a Th1 cellular response is associated with infection control and that antigen-specific memory T cells are necessary for the development of a rapid and strong protective cellular response. The present manuscript reports the analysis of the functional and phenotypic profiles of antigen-specific CD4+ and CD8+ T cells from patients cured of cutaneous leishmaniasis (CL), patients with an active process of cutaneous leishmaniasis, asymptomatic individuals with a positive Montenegro test and healthy donors (HD). Peripheral blood mononuclear cells (PBMCs) from the patients exhibited a lymphoproliferative capacity after stimulation with total soluble protein from either Leishmania panamensis (SLpA) or Leishmania infantum (SLiA) or with a recombinant paraflagellar rod protein-1 (rPFR1). Higher frequencies of antigen-specific TNAIVE cells, mainly following stimulation with rPFR1, were observed in asymptomatic and cured patients than in patients with active cutaneous leishmaniasis, while T cells from patients with active cutaneous leishmaniasis showed a higher percentage of effector memory T cells (TEM for CD4+ T cells and TEMRA for CD8+ T cells). The amount of antigen-specific CD57+/CD8+ TEMRA cells in patients with active cutaneous leishmaniasis was higher than that in cured patients and asymptomatic subjects. Regarding functionality, a more robust multifunctional CD8+ T cell response was detected in cured patients than in those with active cutaneous leishmaniasis. Moreover, cured patients showed a significant increase in the frequency of cells expressing a Th1-type cytotoxic production profile (IFN-γ+/granzyme-B/+perforin+). Patients with an active leishmaniosis process had a significantly higher frequency of CD8+ T cells expressing the inhibitory CD160 and 2B4 receptors than did cured patients. The expression profile observed in cured patients could be indicative of an imbalance toward a CD8+ Th1 response, which could be associated with infection control; consequently, the determination of this profile could be a useful tool for facilitating the clinical follow-up of patients with cutaneous leishmaniasis. The results also suggest a possible exhaustion process of CD8+ T cells associated with the evolution of Leishmania infection.

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HTNV infection of CD8⁺ T cells is associated with disease progression in HFRS patients.

Publications

HTNV infection of CD8<sup>+</sup> T cells is associated with disease progression in HFRS patients.

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