TITLE

Hepatitis C Virus Infection of T Cells Inhibits Proliferation and Enhances Fas-Mediated Apoptosis by Down-Regulating the Expression of CD44 Splicing Variant 6

AUTHOR(S)
Kondo, Yasuteru; Machida, Keigo; Helene Minyi Liu; Ueno, Yoshiyuki; Kobayashi, Koju; Wakita, Takaji; Shimosegawa, Tooru; Lai, Michael M. C.
PUB. DATE
March 2009
SOURCE
Journal of Infectious Diseases;3/1/2009, Vol. 199 Issue 5, p726
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background. A lymphotropic hepatitis C virus strain (HCV, SB strain, hereafter "SB-HCV") has been shown to infect established T cell lines (Molt-4 and Jurkat) and primary human naive CD4+ T cells. During T cell development and activation, transient expression of CD44 splicing variant 6 (CD44v6) plays a significant role. Methods. SB-HCV was used to infect Molt-4 cells, and their cellular proliferation and CD44 expression was examined. Results. SB-HCV-infected Molt-4 cells expressed a significantly lower level of the CD44v6 isoform. The infected cells could be divided into 2 carboxyfluorescein succinimidyl ester (CFSE) groups, CFSE-high (indicating low proliferation activity; 34.2% of the cells) and CFSE-low (indicating high proliferation activity; 62.5% of the cells), whereas uninfected cells consisted of only a CFSE-low population. Of the CFSE-high cells, 82.4% were positive for the HCV protein NS5A , whereas only 1.2% of the CFSE-low cells were positive for this protein. Among the HCV proteins, NS5A alone caused the down-regulation of CD44v6 expression. After cells were stimulated with phorbol myristate acetate, the amount of phosphorylated mitogen-activated protein (MAP) kinase was significantly reduced in CFSE-high, SB-HCV-infected Molt-4 cells. After Fas ligand stimulation, SB-HCV-infected Molt-4 cells had increased cleavage of caspase 8 and 3 and enhanced apoptosis, compared with the rates of cleavage and apoptosis in control groups, indicating that SB-HCV infection increased Fas-mediated apoptosis. Conclusion. HCV replication in T cells suppresses cellular proliferation and enhances susceptibility to Fas signaling by inhibiting CD44v6 signaling and expression.
ACCESSION #
36666025

 

Related Articles

  • Analysis of Functional Differences between Hepatitis C Virus NS5A of Genotypes 1-7 in Infectious Cell Culture Systems. Scheel, Troels K. H.; Prentoe, Jannick; Carlsen, Thomas H. R.; Mikkelsen, Lotte S.; Gottwein, Judith M.; Bukh, Jens // PLoS Pathogens;May2012, Vol. 8 Issue 5, Special section p1 

    Hepatitis C virus (HCV) is an important cause of chronic liver disease. Several highly diverse HCV genotypes exist with potential key functional differences. The HCV NS5A protein was associated with response to interferon (IFN)-a based therapy, and is a primary target of currently developed...

  • Hepatitis C Virus Induced a Novel Apoptosis-Like Death of Pancreatic Beta Cells through a Caspase 3-Dependent Pathway. Qian Wang; Jizheng Chen; Yun Wang; Xiao Han; Xinwen Chen // PLoS ONE;Jun2012, Vol. 7 Issue 6, p1 

    Epidemiological and experimental studies have suggested that Hepatitis C virus (HCV) infection is associated with the development of type 2 diabetes. Pancreatic beta cell failure is central to the progression of type 2 diabetes. Using virus infection system, we investigate the influence of HCV...

  • Physical and functional interaction between HCV core protein and the different p73 isoforms. Alisi, Anna; Giambartolomei, Stefania; Cupelli, Felicia; Merlo, Paola; Fontemaggi, Giulia; Spaziani, Alessandra; Balsano, Clara // Oncogene;5/1/2003, Vol. 22 Issue 17, p2573 

    Hepatitis C virus (HCV) core protein is a structural viral protein that packages the viral genomic RNA. In addition to this function, HCV core also modulates a number of cellular regulatory functions. In fact, HCV core protein has been found to modulate the expression of the cyclin-dependent...

  • Hepatitis C virus and its roles in cell proliferation. Shimotohno, Kunitada; Watashi, Koichi; Tsuchihara, Katsuya; Fukuda, Katsuhiko; Marusawa, Hiroyuki; Hijikata, Makoto // Journal of Gastroenterology;2002 Supplement 13, Vol. 37, p50 

    Hepatitis C virus (HCV) causes chronic hepatitis and is linked to the development of hepatocellular carcinoma (HCC). The role of HCV infection in the development of HCC remains to be clarified. We analyzed the effect of HCV core protein on modulation of cell proliferation. HCV core protein was...

  • Selective inhibitor of histone deacetylase 6 (tubastatin A) suppresses proliferation of hepatitis C virus replicon in culture of human hepatocytes. Kozlov, M.; Kleymenova, A.; Konduktorov, K.; Malikova, A.; Kochetkov, S. // Biochemistry (00062979);Jul2014, Vol. 79 Issue 7, p637 

    Acetylation of α-tubulin was studied in cultures of human hepatocytes under the influence of selective inhibitors of histone deacetylases HDAC6 and SIRT-2 - tubastatin A and 2-(3-phenethoxyphenylamino)benzamide, respectively. It was found that in hepatocyte cell line HepG2 acetylated...

  • Coinfection with Hepatitis C Virus Increases Lymphocyte Apoptosis in HIV-Infected Patients. Núñez, Marina; Soriano, Vincent; López, Mariola; Ballesteros, Celia; Cascajero, Almudena; Gonzélez-Lahoz, Juan; Benito, Jose Miguel // Clinical Infectious Diseases;11/1/2006, Vol. 43 Issue 9, p1209 

    To test the role of hepatitis C virus (HCV) in CD4 cell depletion in human immunodeficiency virus (HIV)—coinfected patients, T cell apoptosis was measured by annexin V labeling in 31 HIV-infected and 30 HIV-HCV—coinfected patients who were not receiving antiretroviral therapy....

  • Hepatitis C virus core proteins derived from different quasispecies of genotype 1b inhibit the growth of Chang liver cells. Xue-Bing Yan; Xia Feng; Mei-Rong Wan; Zhi Chen; Pavio, Nicole; Brechot, Christian; Lei Mei; Thomas, Baumert F. // World Journal of Gastroenterology;5/14/2008, Vol. 14 Issue 18, p2877 

    AIM: To investigate the influence of different quasispecies of hepatitis C virus (HCV) genotype 1b core protein on growth of Chang liver cells. METHODS: Three eukaryotic expression plasmids (pEGFP-N1/core) that contained different quasispecies truncated core proteins of HCV genotype 1b were...

  • Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma). Soe, Kyaw; Hishikawa, Yoshitaka; Fukuzawa, Yoshitaka; Win, Ne; Yin, Khine San; Win, Khin Maung; Myint, Aye Aye; Koji, Takehiko // Journal of Gastroenterology;Mar2007, Vol. 42 Issue 3, p225 

    The aim of this study was to survey the effect of deposited iron on the cell kinetics of hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) in Myanmar (Burmese) patients. Formalin-fixed and paraffin-embedded liver tissues from 34 Myanmar patients with HCC were used. To detect iron...

  • CD81 is a candidate tumor suppressor gene in human gastric cancer. Yoo, Tae-Hyoung; Ryu, Byung-Kyu; Lee, Min-Goo; Chi, Sung-Gil // Cellular Oncology (2211-3428);Apr2013, Vol. 36 Issue 2, p141 

    Background: CD81 is a transmembrane protein that serves as a putative receptor for hepatitis C virus. In addition, CD81 has been suggested to be involved in a broad range of other cellular functions. Its putative implication in tumorigenesis has so far, however, remained largely unexplored. To...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics