scholarly journals Complement Potentiates Immune Sensing of HIV-1 and Early Type I Interferon Responses

mBio ◽  
2021 ◽  
Author(s):  
Wilfried Posch ◽  
Marta Bermejo-Jambrina ◽  
Marion Steger ◽  
Christina Witting ◽  
Gabriel Diem ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Therapeutic Interventions ◽  
Complement Receptor ◽  
Type I ◽  
Early Type ◽  
Antiviral Immune Response ◽  
Immune Sensing ◽  
Interferon Responses ◽  
Hiv 1 ◽  
Subsequent Opening

Importantly, our study highlights an unusual target on DCs—the α chain of complement receptor 4 (CR4) (CD11c)—for therapeutic interventions in HIV-1 treatment. Targeting CD11c on DCs mediated a potent antiviral immune response via clustering of CR4 and CCR5 and subsequent opening of an antiviral recognition pathway in DCs via MAVS.

scholarly journals Early type I Interferon response induces upregulation of human β-defensin 1 during acute HIV-1 infection

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0173161 ◽  
Author(s):  
Björn Corleis ◽  
Antonella C. Lisanti ◽  
Christian Körner ◽  
Abigail E. Schiff ◽  
Eric S. Rosenberg ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Early Type ◽  
Acute Hiv ◽  
Hiv 1

scholarly journals Hantavirus Regulation of Type I Interferon Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Valery Matthys ◽  
Erich R. Mackow
Keyword(s):  
Type I Interferon ◽  
Viral Proteins ◽  
Therapeutic Interventions ◽  
Type I ◽  
Human Endothelial Cells ◽  
Protein Targets ◽  
Interferon Stimulated Genes ◽  
Interferon Induction ◽  
Interferon Responses ◽  
Irf3 Activation

Hantaviruses primarily infect human endothelial cells (ECs) and cause two highly lethal human diseases. Early addition of Type I interferon (IFN) to ECs blocks hantavirus replication and thus for hantaviruses to be pathogenic they need to prevent early interferon induction. PHV replication is blocked in human ECs, but not inhibited in IFN deficient VeroE6 cells and consistent with this, infecting ECs with PHV results in the early induction of IFNβand an array of interferon stimulated genes (ISGs). In contrast, ANDV, HTNV, NY-1V and TULV hantaviruses, inhibit early ISG induction and successfully replicate within human ECs. Hantavirus inhibition of IFN responses has been attributed to several viral proteins including regulation by the Gn proteins cytoplasmic tail (Gn-T). The Gn-T interferes with the formation of STING-TBK1-TRAF3 complexes required for IRF3 activation and IFN induction, while the PHV Gn-T fails to alter this complex or regulate IFN induction. These findings indicate that interfering with early IFN induction is necessary for hantaviruses to replicate in human ECs, and suggest that additional determinants are required for hantaviruses to be pathogenic. The mechanism by which Gn-Ts disrupt IFN signaling is likely to reveal potential therapeutic interventions and suggest protein targets for attenuating hantaviruses.

scholarly journals Type I Interferon Responses by HIV-1 Infection: Association with Disease Progression and Control

2018 ◽  
Vol 8 ◽  
Author(s):  
Andrew Soper ◽  
Izumi Kimura ◽  
Shumpei Nagaoka ◽  
Yoriyuki Konno ◽  
Keisuke Yamamoto ◽  
...  
Keyword(s):  
Disease Progression ◽  
Type I Interferon ◽  
Type I ◽  
And Control ◽  
Interferon Responses ◽  
Hiv 1

scholarly journals Investigation of type I interferon responses in ANCA-associated vasculitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Isabella Batten ◽  
Mark W. Robinson ◽  
Arthur White ◽  
Cathal Walsh ◽  
Barbara Fazekas ◽  
...  
Keyword(s):  
Protein Expression ◽  
Type I Interferon ◽  
Contributory Factor ◽  
Type I ◽  
Healthy Controls ◽  
Type I Ifn ◽  
Serum Samples ◽  
Anca Associated Vasculitis ◽  
Clinical Measurements ◽  
Interferon Responses

AbstractType I interferon (IFN) dysregulation is a major contributory factor in the development of several autoimmune diseases, termed type I interferonopathies, and is thought to be the pathogenic link with chronic inflammation in these conditions. Anti-neutrophil cytoplasmic antibody (ANCA)-Associated Vasculitis (AAV) is an autoimmune disease characterised by necrotising inflammation of small blood vessels. The underlying biology of AAV is not well understood, however several studies have noted abnormalities in type I IFN responses. We hypothesised that type I IFN responses are systemically dysregulated in AAV, consistent with features of a type I interferonopathy. To investigate this, we measured the expression of seven interferon regulated genes (IRGs) (ISG15, SIGLEC1, STAT1, RSAD2, IFI27, IFI44L and IFIT1) in peripheral blood samples, as well as three type I IFN regulated proteins (CXCL10, MCP-1 and CCL19) in serum samples from AAV patients, healthy controls and disease controls. We found no difference in type I IFN regulated gene or protein expression between AAV patients and healthy controls. Furthermore, IRG and IFN regulated protein expression did not correlate with clinical measurements of disease activity in AAV patients. Thus, we conclude that systemic type I IFN responses are not key drivers of AAV pathogenesis and AAV should not be considered a type I interferonopathy.

scholarly journals Alteration of type I interferon response is associated with subclinical atherosclerosis in virologically suppressed HIV‐1‐infected male patients

2021 ◽  
Author(s):  
Letizia Santinelli ◽  
Gabriella De Girolamo ◽  
Cristian Borrazzo ◽  
Paolo Vassalini ◽  
Claudia Pinacchio ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Subclinical Atherosclerosis ◽  
Interferon Response ◽  
Type I ◽  
Infected Male ◽  
Male Patients ◽  
Hiv 1

scholarly journals 435 Autocrine IFN-k maintains baseline type I interferon responses in keratinocytes in a Tyk2 dependent manner

2016 ◽  
Vol 136 (9) ◽  
pp. S234
Author(s):  
M. Sarkar ◽  
L.C. Tsoi ◽  
X. Xing ◽  
L. Yun ◽  
P. Harms ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Dependent Manner ◽  
Interferon Responses

scholarly journals Type I interferon responses to ischemic injury begin in the bone marrow of mice and humans and depend on Tet2, Nrf2, and Irf3

2019 ◽  
Author(s):  
David M. Calcagno ◽  
Richard P. Ng ◽  
Avinash Toomu ◽  
Claire Zhang ◽  
Kenneth Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Type I Interferon ◽  
Tissue Injury ◽  
Type I ◽  
Blood Neutrophils ◽  
Clinical Biomarker ◽  
Acute Mi ◽  
Molecular Patterns ◽  
Interferon Responses ◽  
Myeloid Progenitors

AbstractSterile tissue injury locally activates innate immune responses via interactions with damage associated molecular patterns (DAMPs). Here, by analyzing ∼120K single cell transcriptomes after myocardial infarction (MI) in mice and humans, we show neutrophil and monocyte subsets induce type I interferon (IFN) stimulated genes (ISGs) in myeloid progenitors of the bone marrow, far from the site of injury. In patients with acute MI, peripheral blood neutrophils and monocytes express ISGs at levels far beyond healthy individuals and comparable to patients with lupus. In the bone marrow of Tet2-/- mice, ISGs are spontaneously induced in myeloid progenitors and their progeny. In the heart, IFN responses are negatively regulated by Ccr2- resident macrophages in a Nrf2-dependent fashion. Our results show post-MI IFN signaling begins in the bone marrow, implicate multiple transcription factors in its regulation (Tet2, Irf3, Nrf2), and provide a clinical biomarker (ISG score) for studying post-MI IFN signaling in patients.

Sign in / Sign up

Export Citation Format

Share Document