SARS-CoV-2 Isolates Show Impaired Replication in Human Immune Cells but Differential Ability to Replicate and Induce Innate Immunity in Lung Epithelial Cells

Jiang, Miao; Kolehmainen, Pekka; Kakkola, Laura; Maljanen, Sari; Melén, Krister; Smura, Teemu; Julkunen, Ilkka; Österlund, Pamela

doi:10.1128/spectrum.00774-21

Cited by 16 publications

(15 citation statements)

References 75 publications

(97 reference statements)

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“…-2 variants. SARS-CoV-2 isolates FIN25-20 (B.1, D614G variant, MW717675.1 and EPI_ISL_412971)25 , FIN37-21 (B.1.617.2, Delta variant, MZ945494 and EPI_ISL_2557176)26 and FIN55-21 (B.1.1.529, Omicron BA.1 variant, EPI_ISL_8768822.2) were isolated from SARS-CoV-2 PCR-positive nasopharyngeal samples by incubation with VeroE6 (for FIN25-20) or VeroE6-TMPRSS2-H10 cells27 (for FIN37-21 and FIN55-21) and further passaged in VeroE6-TMPRSS2-H10 cells in DMEM supplemented with 2% FBS, 2 mM Lglutamine, and penicillin-streptomycin. Titration of virus stocks was done using Median Tissue Culture Infectious Dose (TCID 50 ) assay.…”

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confidence: 99%

Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants

et al. 2022

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Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.

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confidence: 99%

Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants

et al. 2022

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“…In order to characterize the profile of host cell infectivity by SARS-CoV-2, HBMEC and Vero E6 cells were infected in the presence or not of serine endoprotease TPCK trypsin (1 μg/ml), which was shown to increase infectivity in Calu-3 cells, a permissive cell line for the efficient replication of SARS-CoV-2 (Jiang et al, 2021). Cultures were infected at different multiplicities of infection (MOIs) of 0.01, 0.1, 1 and 2 and supernatants were collected at 6-, 24-, 48- and 72-hours post-infection (hpi) and analyzed by RT-qPCR for quantification of viral E gene ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling

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et al. 2022

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Neurological effects of COVID-19 and long-COVID-19 as well as neuroinvasion by SARS-CoV-2 still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro infection by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the Blood-Brain Barrier. Despite the low to non- productive viral replication, SARS-CoV-2-infected cultures displayed increased apoptotic cell death and tight junction protein expression and immunolocalization. Transcriptomic profiling of infected cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression, and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.

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“…Previous data have shown inability of SARS-CoV-2 to replicate in various immune cells ( 36 ). Also, proteomic and genomic data clearly highlighted the absence of ACE2 receptor on the basophils ( 37 ).…”

Section: Discussionmentioning

confidence: 97%

SARS-CoV-2 Induces Cytokine Responses in Human Basophils

et al. 2022

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Basophils play a key role in the orientation of immune responses. Though the interaction of SARS-CoV-2 with various immune cells has been relatively well studied, the response of basophils to this pandemic virus is not characterized yet. In this study, we report that SARS-CoV-2 induces cytokine responses and in particular IL-13, in both resting and IL-3 primed basophils. The response was prominent under IL-3 primed condition. However, either SARS-CoV-2 or SARS-CoV-2-infected epithelial cells did not alter the expression of surface markers associated with the activation of basophils, such as CD69, CD13 and/or degranulation marker CD107a. We also validate that human basophils are not permissive to SARS-CoV-2 replication. Though increased expression of immune checkpoint molecule PD-L1 has been reported on the basophils from COVID-19 patients, we observed that SARS-CoV-2 does not induce PD-L1 on the basophils. Our data suggest that basophil cytokine responses to SARS-CoV-2 might help in reducing the inflammation and also to promote antibody responses to the virus.

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SARS-CoV-2 Isolates Show Impaired Replication in Human Immune Cells but Differential Ability to Replicate and Induce Innate Immunity in Lung Epithelial Cells

Cited by 16 publications

References 75 publications

Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants

Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants

SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling

SARS-CoV-2 Induces Cytokine Responses in Human Basophils

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