scholarly journals Interferon-alpha or -beta facilitates SARS-CoV-2 pulmonary vascular infection by inducing ACE2

Angiogenesis ◽  
2021 ◽  
Author(s):  
Timothy Klouda ◽  
Yuan Hao ◽  
Hyunbum Kim ◽  
Jiwon Kim ◽  
Judith Olejnik ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Vascular Complications ◽  
Surface Expression ◽  
Interferon Γ ◽  
Endothelial Damage ◽  
Interferon Response ◽  
Cell Surface Expression ◽  
Minimal Cell ◽  
Pulmonary Endothelium ◽  
Endothelial Cell Cultures

AbstractSevere viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a hyperinflammatory state typified by elevated circulating pro-inflammatory cytokines, frequently leading to potentially lethal vascular complications including thromboembolism, disseminated intracellular coagulopathy and vasculitis. Though endothelial infection and subsequent endothelial damage have been described in patients with fatal COVID-19, the mechanism by which this occurs remains elusive, particularly given that, under naïve conditions, pulmonary endothelial cells demonstrate minimal cell surface expression of the SARS-CoV-2 binding receptor ACE2. Herein we describe SARS-CoV-2 infection of the pulmonary endothelium in postmortem lung samples from individuals who died of COVID-19, demonstrating both heterogeneous ACE2 expression and endothelial damage. In primary endothelial cell cultures, we show that SARS-CoV-2 infection is dependent on the induction of ACE2 protein expression and that this process is facilitated by type 1 interferon-alpha (IFNα) or -beta(β)—two of the main anti-viral cytokines induced in severe SARS-CoV-2 infection—but not significantly by other cytokines (including interleukin 6 and interferon γ/λ). Our findings suggest that the stereotypical anti-viral interferon response may paradoxically facilitate the propagation of COVID-19 from the respiratory epithelium to the vasculature, raising concerns regarding the use of exogenous IFNα/β in the treatment of patients with COVID-19.

Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1137-1144 ◽  
Author(s):  
Deepa Hariharan ◽  
Steven D. Douglas ◽  
Benhur Lee ◽  
Jian-Ping Lai ◽  
Donald E. Campbell ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hiv Infection ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Interferon Γ ◽  
Mononuclear Phagocytes ◽  
Cell Surface Expression ◽  
Ccr5 Expression ◽  
Hiv Entry ◽  
Ifn Γ

Abstract The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-γ (IFN-γ) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-γ showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1β, confirming the functional relevance of IFN-γ–induced CCR5 expression. However, IFN-γ suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-γ inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-γ on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-γ–induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1β) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.

From transcription to cell surface expression, the induction of MHC class II I-Aα by interferon-γ in macrophages is regulated at different levels

2001 ◽  
Vol 53 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Martin Cullell-Young ◽  
Marta Barrachina ◽  
Carlos López-López ◽  
Eduard Goñalons ◽  
Jorge Lloberas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class Ii ◽  
Surface Expression ◽  
Class Ii ◽  
Interferon Γ ◽  
Cell Surface Expression ◽  
Different Levels

scholarly journals Induction of Lectin-like Transcript 1 (LLT1) Protein Cell Surface Expression by Pathogens and Interferon-γ Contributes to Modulate Immune Responses

2011 ◽  
Vol 286 (44) ◽  
pp. 37964-37975 ◽  
Author(s):  
Claire Germain ◽  
Anders Meier ◽  
Teis Jensen ◽  
Perrine Knapnougel ◽  
Gwenola Poupon ◽  
...  
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Surface Expression ◽  
Interferon Γ ◽  
Cell Surface Expression ◽  
Protein Cell

Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1137-1144 ◽  
Author(s):  
Deepa Hariharan ◽  
Steven D. Douglas ◽  
Benhur Lee ◽  
Jian-Ping Lai ◽  
Donald E. Campbell ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hiv Infection ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Interferon Γ ◽  
Mononuclear Phagocytes ◽  
Cell Surface Expression ◽  
Ccr5 Expression ◽  
Hiv Entry ◽  
Ifn Γ

The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-γ (IFN-γ) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-γ showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1β, confirming the functional relevance of IFN-γ–induced CCR5 expression. However, IFN-γ suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-γ inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-γ on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-γ–induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1β) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.

Interferon-γ rescues HLA class Ia cell surface expression in term villous trophoblast cells by inducing synthesis of TAP proteins

1997 ◽  
Vol 27 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Anne-Marie Rodriguez ◽  
Valérie Mallet ◽  
Françoise Lenfant ◽  
Jacques Arnaud ◽  
Maryse Girr ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Interferon Γ ◽  
Cell Surface Expression ◽  
Trophoblast Cells ◽  
Villous Trophoblast

Genetically determined susceptibility to mycobacterial infection

2008 ◽  
Vol 61 (9) ◽  
pp. 1006-1012 ◽  
Author(s):  
S Y Patel ◽  
R Doffinger ◽  
G Barcenas-Morales ◽  
D S Kumararatne
Keyword(s):  
Mycobacterial Infection ◽  
Surface Expression ◽  
Interferon Γ ◽  
Cell Surface Expression ◽  
Interleukin 12 ◽  
Genetic Defects ◽  
Cell Mediated Immunity ◽  
Gene Encoding ◽  
Mycobacterial Infections ◽  
Recessive Mutations

Individuals with impaired cell mediated immunity exhibit increased susceptibility to infections caused by poorly pathogenic mycobacteria (non-tuberculous mycobacteria and BCG), as well as salmonella species. However, these infections may also occur in a disseminated, fatal form, sometimes with a familial distribution, in the absence of any recognised primary or secondary immunodeficiency. Genetic analysis of affected families has defined mutations in seven different genes participating in the interleukin 12 (IL12) dependent, high output interferon γ (IFNγ) pathway. The first category of defect is mutations in the IFNγR1 or R2 genes, resulting in defective expression or function of the IFNγ receptor. The second category of mutations abrogates the cell surface expression IL12Rβ1gene, resulting in the inability to respond to IL12. The third category of defect is the inability to produce IL12, due to deletion within the gene coding for the inducible chain of IL12 (IL12-p40). Patients with X-linked recessive mutations of the gene encoding the NFκB essential modulator may also develop mycobacterial infections, although they usually have a more complex phenotype and are susceptible to a broad spectrum of pathogens. Mutations of the gene encoding the signal transducing molecule STAT1, which impairs the ability to respond to IFNγ, and mutations of the gene encoding TYK2 (which is associated with a failure to respond to IL12), are both rare genetic defects predisposing to mycobacterial infections. This review summarises the clinical spectrum seen in this group of patients and indicates a strategy for the identification of putative genetic defects in the type-1 cytokine pathway.

scholarly journals HIV Vpu Interferes with NF-κB Activity but Not with Interferon Regulatory Factor 3

2015 ◽  
Vol 89 (19) ◽  
pp. 9781-9790 ◽  
Author(s):  
Lara Manganaro ◽  
Elisa de Castro ◽  
Ana M. Maestre ◽  
Kevin Olivieri ◽  
Adolfo García-Sastre ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Surface Expression ◽  
Interferon Regulatory Factor ◽  
Interferon Response ◽  
Cell Surface Expression ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Type 1 Interferon ◽  
Innate Immune Signaling

ABSTRACTThe accessory HIV protein Vpu inhibits a number of cellular pathways that trigger host innate restriction mechanisms. HIV Vpu-mediated degradation of tetherin allows efficient particle release and hampers the activation of the NF-κB pathway thereby limiting the expression of proinflammatory genes. In addition, Vpu reduces cell surface expression of several cellular molecules such as newly synthesized CD4. However, the role of HIV Vpu in regulating the type 1 interferon response to viral infection by degradation of the interferon regulatory factor 3 (IRF3) has been subject of conflicting reports. We therefore systematically investigated the expression of IRF3 in primary CD4+T cells and macrophages infected with HIV at different time points. In addition, we also tested the ability of Vpu to interfere with innate immune signaling pathways such as the NF-κB and the IRF3 pathways. We report here that HIV Vpu failed to degrade IRF3 in infected primary cells. Moreover, we observed that HIV NL4.3 Vpu had no effect on IRF3-dependent gene expression in reporter assays. On the other hand, HIV NL4.3 Vpu downmodulated NF-κB-dependent transcription. Mutation of two serines (positions 52 and 56) involved in the binding of NL4.3 Vpu to the βTrCP ubiquitin ligase abolishes its ability to inhibit NF-κB activity. Taken together, these results suggest that HIV Vpu regulates antiviral innate response in primary human cells by acting specifically on the NF-κB pathway.IMPORTANCEHIV Vpu plays a pivotal role in enhancing HIV infection by counteraction of Tetherin. However, Vpu also regulates host response to HIV infection by hampering the type 1 interferon response. The molecular mechanism by which Vpu inhibits the interferon response is still controversial. Here we report that Vpu affects interferon expression by inhibiting NF-κB activity without affecting IRF3 levels or activity. These data suggest that Vpu facilitates HIV infection by regulating NF-κB transcription to levels sufficient for viral transcription while limiting cellular responses to infection.

Interferon-γ Decreases Cell Surface Expression of Galactosyl Ceramide, the Receptor for HIV-1 GP120 on Human Colonic Epithelial Cells

Virology ◽  
1994 ◽  
Vol 204 (2) ◽  
pp. 550-557 ◽  
Author(s):  
Nouara Yahi ◽  
Steven L. Spitalnik ◽  
Kelly A. Stefano ◽  
Philippe De Micco ◽  
Francisco Gonzalez-Scarano ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Surface Expression ◽  
Interferon Γ ◽  
Cell Surface Expression ◽  
Colonic Epithelial Cells ◽  
Galactosyl Ceramide ◽  
Hiv 1
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