scholarly journals Of mice, rats, and men: Small animal model of hepatitis C virus infection

Hepatology ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 374-376
Author(s):  
Arash Grakoui ◽  
Christopher M. Walker
Author(s):  
Muttiah Barathan ◽  
Rosmawati Mohamed ◽  
Yean K. Yong ◽  
Meganathan Kannan ◽  
Jamuna Vadivelu ◽  
...  

Hepatitis C virus (HCV) represents a challenging global health threat in ~200 million infected individuals. Clinical data suggests that only ~10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts a myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence that includes, but not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here, we discussed a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.


1999 ◽  
Vol 43 (2) ◽  
pp. 347-353 ◽  
Author(s):  
Hong Zhang ◽  
Ronnie Hanecak ◽  
Vickie Brown-Driver ◽  
Raana Azad ◽  
Boyd Conklin ◽  
...  

ABSTRACT Hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide. Current treatments are not curative for most infected individuals, and there is an urgent need for both novel therapeutic agents and small-animal models which can be used to evaluate candidate drugs. A small-animal model of HCV gene expression was developed with recombinant vaccinia virus vectors. VHCV-IRES (internal ribosome entry site) is a recombinant vaccinia viral vector containing the HCV 5′ nontranslated region (5′-NTR) and a portion of the HCV core coding region fused to the firefly luciferase gene. Intraperitoneal injection of VHCV-IRES produced high levels of luciferase activity in the livers of BALB/c mice. Antisense oligonucleotides complementary to the HCV 5′-NTR and translation initiation codon regions were then evaluated for their effects on the expression of these target HCV sequences in BALB/c mice infected with the vaccinia virus vector. Treatment of VHCV-IRES-infected mice with 20-base phosphorothioate oligonucleotides complementary to the sequence surrounding the HCV initiation codon (nucleotides 330 to 349) specifically reduced luciferase expression in the livers in a dose-dependent manner. Inhibition of HCV reporter gene expression in this small-animal model suggests that antisense oligonucleotides may provide a novel therapy for treatment of chronic HCV infection.


Uirusu ◽  
2015 ◽  
Vol 65 (2) ◽  
pp. 255-262
Author(s):  
Kyoko TSUKIYAMA-KOHARA ◽  
Michinori KOHARA

2013 ◽  
Vol 4 ◽  
Author(s):  
Laurent Mailly ◽  
Eric Robinet ◽  
Philip Meuleman ◽  
Thomas F. Baumert ◽  
Mirjam B. Zeisel

Hepatology ◽  
2002 ◽  
Vol 35 (3) ◽  
pp. 722-724 ◽  
Author(s):  
Volker Brass ◽  
Hubert E. Blum ◽  
Darius Moradpour

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 165 ◽  
Author(s):  
Muttiah Barathan ◽  
Rosmawati Mohamed ◽  
Yean Yong ◽  
Meganathan Kannan ◽  
Jamuna Vadivelu ◽  
...  

Hepatitis C virus (HCV) represents a challenging global health threat to ~200 million infected individuals. Clinical data suggest that only ~10–15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence, which includes, but is not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here we discuss a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.


1997 ◽  
Vol 96 (2) ◽  
pp. 427-428 ◽  
Author(s):  
FREDERICO SILVESTRI ◽  
GIOVANNI BARILLARI ◽  
RENATO FANIN ◽  
FLAVIA SALMASO ◽  
LAURA INFANTI ◽  
...  

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