The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Apr. 30, 2019

Filed:

Jan. 07, 2015
Applicant:

Frontier Bio-drug Development Limited, Tortola, VG;

Inventor:

Chen-Lung Lin, Kaohsiung, TW;

Attorney:
Primary Examiner:
Int. Cl.
CPC ...
C12N 7/00 (2006.01); G01N 33/576 (2006.01); C12N 5/0775 (2010.01); C12Q 1/70 (2006.01); G01N 33/50 (2006.01);
U.S. Cl.
CPC ...
C12N 7/00 (2013.01); C12N 5/0667 (2013.01); C12Q 1/707 (2013.01); G01N 33/5073 (2013.01); G01N 33/5767 (2013.01); C12N 2502/70 (2013.01); C12N 2770/24251 (2013.01); C12Q 2600/136 (2013.01); G01N 2333/186 (2013.01);
Abstract

Hepatitis C virus replication at extrahepatic sites has been suggested; however, complete viral replication has only been confirmed in hepatocytes. Here we show that human adipogenic DLK-1stem cells (hADSC) freshly isolated from HCV-infected individuals contained viral transcripts, replication intermediates and viral antigens in vivo, and viral transcripts increased in supernatants upon prolonged ex vivo culture. Furthermore, naive hADSC isolated from HCV (−) individuals support complete replication of clinical isolates in vitro, and the infection is donor-nonspecific for cells and cross-genotypic for viruses. Viral infection/replication is mediated through CD81, LDL-R, SR-B1, EGFR, Apolipoprotein E, occludin, claudin-1, NPC1L1 and diacylglycerol acetyltransferase-1, and can be inhibited by anti-viral drugs. In addition, the physical properties of hADSC-propagated viral particles resemble clinical isolates more than JFH1/HCVcc, and viruses propagated by in vitro infected hADSC are infectious to primary human hepatocytes. Therefore, hADSC are an in vivo HCV reservoir and represent a novel venue of clinical virus-host interaction. hADSC can also be exploited as a physiologically relevant primary cell culture system to propagate clinical isolates.


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