Dynamic changes in innate immune responses during direct-acting antiviral therapy for HCV infection

2019 ◽  
Vol 26 (3) ◽  
pp. 362-372 ◽  
Author(s):  
Jacinta A. Holmes ◽  
Charles Carlton-Smith ◽  
Arthur Y. Kim ◽  
Emily O. Dumas ◽  
Joelle Brown ◽  
...  
2015 ◽  
Vol 53 (12) ◽  
Author(s):  
C Dembek ◽  
C Russo ◽  
A Grambihler ◽  
J Schattenberg ◽  
T Zimmermann ◽  
...  

2006 ◽  
Vol 80 (2) ◽  
pp. 866-874 ◽  
Author(s):  
Keigo Machida ◽  
Kevin T. H. Cheng ◽  
Vicky M.-H. Sung ◽  
Alexandra M. Levine ◽  
Steven Foung ◽  
...  

ABSTRACT Hepatitis C virus (HCV) induces inflammatory signals, leading to hepatitis, hepatocellular carcinomas, and lymphomas. The mechanism of HCV involvement in the host's innate immune responses has not been well characterized. In this study, we analyzed expression and regulation of the entire panel of toll-like receptors (TLRs) in human B cells following HCV infection in vitro. Among all of the TLRs (TLRs 1 to 10) examined, only TLR4 showed an altered expression (a three- to sevenfold up-regulation) after HCV infection. Peripheral blood mononuclear cells from HCV-infected individuals also showed a higher expression level of TLR4 compared with those of healthy individuals. HCV infection significantly increased beta interferon (IFN-β) and interleukin-6 (IL-6) secretion from B cells, particularly after lipopolysaccharide stimulation. The increased IFN-β and IL-6 production was mediated by TLR4 induction, since the introduction of the small interfering RNA against TLR4 specifically inhibited the HCV-induced cytokine production. Among all of the viral proteins, only NS5A caused TLR4 induction in hepatocytes and B cells. NS5A specifically activated the promoter of the TLR4 gene in both hepatocytes and B cells. In conclusion, HCV infection directly induces TLR4 expression and thereby activates B cells, which may contribute to the host's innate immune responses.


AIDS Care ◽  
2019 ◽  
Vol 32 (6) ◽  
pp. 762-769 ◽  
Author(s):  
A. Piekarska ◽  
E. Jabłonowska ◽  
A. Garlicki ◽  
M. Sitko ◽  
W. Mazur ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-1
Author(s):  
Armando Calogero ◽  
Evangelista Sagnelli ◽  
Massimiliano Creta ◽  
Silvia Angeletti ◽  
Gaia Peluso ◽  
...  

Author(s):  
Hiroshi Takahashi ◽  
Tatsuo Kanda ◽  
Naoki Matsumoto ◽  
Taku Mizutani ◽  
Tomohiro Kaneko ◽  
...  

In the present Japanese female patient with alanine aminotransferase (ALT) elevation greater than 500 IU/l during combination therapy with grazoprevir/elbasvir against HCV infection, this therapy was stopped at week 8. However, sustained virologic response was achieved. In the present report, we also focused on ALT elevation and sustained virologic response during and after antiviral therapies. The current case report demonstrates that careful monitoring of liver function tests may be required during direct-acting antiviral therapy against HCV infection because it is now possible to treat patients with polypharmacy, patients with chronic kidney disease, patients with cirrhosis or aged patients. Careful attention should be paid to liver damage as one of the adverse events in the use of HCV nonstructural protein 3/4A protease inhibitors. Of interest, many publications have addressed both ALT elevations during direct-acting antiviral therapy and viral clearance in relatively short treatment durations.


IDCases ◽  
2018 ◽  
Vol 14 ◽  
pp. e00450 ◽  
Author(s):  
Cátia Dias ◽  
Filipa Duarte-Ribeiro ◽  
Sara Pipa ◽  
Ana Rita Barbosa ◽  
Margarida Mota ◽  
...  

2015 ◽  
Author(s):  
Athma A. Pai ◽  
Golshid Baharian ◽  
Ariane Pagé Sabourin ◽  
Jessica F. Brinkworth ◽  
Yohann Nédélec ◽  
...  

ABSTRACTThe contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains poorly studied despite emerging examples of their role as regulators of immune defenses. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with two live bacteria. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, and found global shifts towards (i) the inclusion of cassette exons and (ii) shorter 3’ UTRs. Using complementary data collected in non-human primates, we show that these features are evolutionarily conserved among primates. Finally, our results suggest that the pervasive usage of shorter 3’ UTRs is a mechanism for particular genes to evade repression by immune-activated miRNAs. Collectively, our results show that dynamic changes in RNA processing play a key role in the regulation of innate immune responses.


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