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SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients.

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that appears as both signature and prognosis of disease severity outcome. Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication. We found that monocytes, as well as both B and T lymphocytes, were susceptible to SARS-CoV-2 infection in vitro, accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis. In addition, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019 (COVID-19) patients. The rates of SARS-CoV-2-infected monocytes in peripheral blood mononuclear cells from COVID-19 patients increased over time from symptom onset, with SARS-CoV-2-positive monocytes, B cells, and CD4+ T lymphocytes also detected in postmortem lung tissue. These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in COVID-19 patients might have important implications for disease pathogenesis and progression, immune dysfunction, and virus spread within the host.

SUBMITTER: Pontelli MC

PROVIDER: S-EPMC9384834 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients.

Pontelli Marjorie C MC Castro Ítalo A ÍA Martins Ronaldo B RB La Serra Leonardo L Veras Flávio P FP Nascimento Daniele C DC Silva Camila M CM Cardoso Ricardo S RS Rosales Roberta R Gomes Rogério R Lima Thais M TM Souza Juliano P JP Vitti Brenda C BC Caetité Diego B DB de Lima Mikhael H F MHF Stumpf Spencer D SD Thompson Cassandra E CE Bloyet Louis-Marie LM Toller-Kawahisa Juliana E JE Giannini Marcela C MC Bonjorno Letícia P LP Lopes Maria I F MIF Batah Sabrina S SS Siyuan Li L Luppino-Assad Rodrigo R Almeida Sergio C L SCL Oliveira Fabiola R FR Benatti Maíra N MN Pontes Lorena L F LLF Santana Rodrigo C RC Vilar Fernando C FC Auxiliadora-Martins Maria M Shi Pei-Yong PY Cunha Thiago M TM Calado Rodrigo T RT Alves-Filho José C JC Zamboni Dario S DS Fabro Alexandre T AT Louzada-Junior Paulo P Oliveira Rene D R RDR Whelan Sean P J SPJ Cunha Fernando Q FQ Arruda Eurico E

Journal of molecular cell biology 20220801 4

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that appears as both signature and prognosis of disease severity outcome. Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication. We found that monoc ...[more]

PMID: 35451490

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Project description:Accumulated evidence indicates that immune cells can support the replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to which individual immune cell types support HCV propagation and on characteristics of virus assembly. We investigated the ability of authentic, patient-derived HCV to infect in vitro two closely related but functionally distinct immune cell types, CD4+ and CD8+ T lymphocytes, and assessed the properties of the virus produced by these cells. The HCV replication system in intermittently mitogen-stimulated T cells was adapted to infect primary human CD4+ or CD8+ T lymphocytes. HCV replicated in both cell types although at significantly higher levels in CD4+ than in CD8+ T cells. Thus, the HCV RNA replicative (negative) strand was detected in CD4+ and CD8+ cells at estimated mean levels ± standard errors of the means of 6.7 × 102 ± 3.8 × 102 and 1.2 × 102 ± 0.8 × 102 copies/μg RNA, respectively (P < 0.0001). Intracellular HCV NS5a and/or core proteins were identified in 0.9% of CD4+ and in 1.2% of CD8+ T cells. Double staining for NS5a and T cell type-specific markers confirmed that transcriptionally competent virus replicated in both cell types. Furthermore, an HCV-specific protease inhibitor, telaprevir, inhibited infection in both CD4+ and CD8+ cells. The emergence of unique HCV variants and the release of HCV RNA-reactive particles with biophysical properties different from those of virions in plasma inocula suggested that distinct viral particles were assembled, and therefore, they may contribute to the pool of circulating virus in infected patients.IMPORTANCE Although the liver is the main site of HCV replication, infection of the immune system is an intrinsic characteristic of this virus independent of whether infection is symptomatic or clinically silent. Many fundamental aspects of HCV lymphotropism remain uncertain, including the degree to which different immune cells support infection and contribute to virus diversity. We show that authentic, patient-derived HCV productively replicates in vitro in two closely related but functionally distinct types of T lymphocytes, CD4+ and CD8+ cells. The display of viral proteins and unique variants, the production of virions with biophysical properties distinct from those in plasma serving as inocula, and inhibition of replication by an antiviral agent led us to ascertain that both T cell subtypes supported virus propagation. Infection of CD4+ and CD8+ T cells, which are central to adaptive antiviral immune responses, can directly affect HCV clearance, favor virus persistence, and decisively influence the development and progression of hepatitis C.

Dataset Information

SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients.

Publications

SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients.

Similar Datasets

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