Acute expression of hepatitis C core protein in adult mouse liver: Mitochondrial stress and apoptosis

Chang, Mau‐Song; Chen, Jeng-Chang; Chang, Ming‐Ling; Yeh, Chau‐Ting; Lin, Wei-Wen; Liang, Chun-Kai; Huang, Shiu-Feng; Dang, Kim; Chiu, Cheng‐Tang; Lin, Deng‐Yn

doi:10.1080/00365520701875987

Cited by 14 publications

(15 citation statements)

References 32 publications

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“…The apoptotic property of the genotype 1a core protein has yet to be studied using the JFH-1-based infectious clone system, although previous studies have attributed both prosurvival and proapoptotic properties to it (25,30,46,57). Similar observations also have been described in overexpression studies using the genotype 1b core protein and appear to be dependent on the death stimuli and types of cells used (3,9,10,36,49,53,56,60,76). Several studies have identified domains or regions within the core protein that interfere with specific apoptosis pathways.…”

supporting

confidence: 65%

The Hepatitis C Virus Core Protein Contains a BH3 Domain That Regulates Apoptosis through Specific Interaction with Human Mcl-1

Mohd-Ismail

Deng

Sukumaran

et al. 2009

J Virol

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The hepatitis C virus (HCV) core protein is known to modulate apoptosis and contribute to viral replication and pathogenesis. In this study, we have identified a Bcl-2 homology 3 (BH3) domain in the core protein that is essential for its proapoptotic property. Coimmunoprecipitation experiments showed that the core protein interacts specifically with the human myeloid cell factor 1 (Mcl-1), a prosurvival member of the Bcl-2 family, but not with other prosurvival members (Bcl-X L and Bcl-w). Moreover, the overexpression of Mcl-1 protects against core-induced apoptosis. By using peptide mimetics, core was found to release cytochrome c from isolated mitochondria when complemented with Bad. Thus, core is a bona fide BH3-only protein having properties similar to those of Noxa, a BH3-only member of the Bcl-2 family that binds preferentially to Mcl-1. There are three critical hydrophobic residues in the BH3 domain of the core protein, and they are essential for the proapoptotic property of the core protein. Furthermore, the genotype 1b core protein is more effective than the genotype 2a core protein in inducing apoptosis due to a single-amino-acid difference at one of these hydrophobic residues (residue 119). Replacing this residue in the J6/JFH-1 infectious clone (genotype 2a) with the corresponding amino acid in the genotype 1b core protein produced a mutant virus, J6/JFH-1(V119L), which induced significantly higher levels of apoptosis in the infected cells than the parental J6/JFH-1 virus. Furthermore, the core protein of J6/JFH-1(V119L), but not that of J6/JFH-1, interacted with Mcl-1 in virus-infected cells. Taken together, the core protein is a novel BH3-only viral homologue that contributes to the induction of apoptosis during HCV infection.

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supporting

confidence: 65%

The Hepatitis C Virus Core Protein Contains a BH3 Domain That Regulates Apoptosis through Specific Interaction with Human Mcl-1

Mohd-Ismail

Deng

Sukumaran

et al. 2009

J Virol

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“…During chronic inflammation, this balance is altered. Studies have shown that mitochondrial ROS production increases with viral infection [96], and NO and its derivatives (RNS) are produced in copious quantities in inflamed tissue [97]. In addition, the mechanisms for removing ROS and RNS are downregulated.…”

Section: Inflammation and Rosmentioning

confidence: 99%

HPV-DNA Integration and Carcinogenesis: Putative Roles For Inflammation And Oxidative Stress

et al. 2010

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HPV-DNA integration into cellular chromatin is usually a necessary event in the pathogenesis of HPV-related cancer; however, the mechanism of integration has not been clearly defined. Breaks must be created in both the host DNA and in the circular viral episome for integration to occur, and studies have shown that viral integration is indeed increased by the induction of DNA double strand breaks. Inflammation generates reactive oxygen species, which in turn have the potential to create such DNA strand breaks. It is plausible that these breaks enable a greater frequency of HPV-DNA integration, and in this way contribute to carcinogenesis. Consistent with this idea, coinfections with certain sexually transmitted diseases cause cervical inflammation, and have also been identified as cofactors in the progression to cervical cancer. This article examines the idea that inflammation facilitates HPV-DNA integration into cellular chromatin through the generation of reactive oxygen species, thereby contributing to carcinogenesis. Keywordsbacterial co-infection; cervical cancer; DNA damage; HPV; inflammation; integration; oropharyngeal cancer; oxidative stress; papillomavirus; viral Human papillomavirusesHuman papillomaviruses (HPVs) are a group of circular, dsDNA viruses that infect epithelial cells [1], and are divided into more than 100 different genotypes based on sequence differences within their L1 gene [2]. Of the 100 genotypes of HPV, at least 30 are sexually transmitted and infect the genital areas of both men and women. A subset of these genotypes causes anogenital warts, which can be either benign or cancerous. Consequently, HPV types are designated 'low risk' or 'high risk' (HR), based on whether they are known to cause benign or cancerous lesions [3]. Virtually all cases of cervical and anogenital cancer are caused by approximately 15 HR genotypes of HPV [4][5][6][7]. Of the HR genotypes, HPV16, HPV18, HPV31 and HPV33 are associated with 90% of all cases of cervical cancer, and HPV DNA is present in more than 90% of premalignant and malignant squamous lesions of the uterine cervix [8,9]. HPV type 16 is the most prevalent type and is associated with more than 50% of all cases of cervical cancers [10,11].Papillomavirus genomes consist of double-stranded circular DNA of approximately 8 kb in size, containing approximately eight open reading frames (ORFs), which are transcribed as polycistronic messages from a single DNA strand. The genome can be divided into three regions: an early region, a late region and a long control region. The early region encodes

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“…In addition, in HCV transgenic mice, HCV core protein localizes to the mitochondria and promotes ROS generation91,92.…”

Section: Triggering Apoptosismentioning

confidence: 99%

Apoptosis in animal models of virus-induced disease

2009

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Apoptosis is associated with virus-induced human diseases of the central nervous system, heart and liver, and causes substantial morbidity and mortality. Although virus-induced apoptosis is well characterized in individual cells in cell culture, virus-induced apoptosis in vivo and the role of apoptosis in virus-induced disease is not well established. This Review focuses on animal models of virus-induced diseases of the central nervous system, heart and liver that provide insights into the role of apoptosis in pathogenesis, the pathways involved and the potential therapeutic implications.Apoptosis plays an essential part in homeostasis, development and human disease by facilitating the removal of unwanted, damaged or infected cells. However, apoptosis may also have a pathogenic role by contributing to cell death and tissue injury. Apoptotic cell death occurs in a wide range of human viral infections, including infections of the central nervous system (CNS), heart and liver. For example, apoptosis can be detected in the brains of patients with virus-induced CNS disease, including patients with HIV-1-associated dementia 1 , herpes simplex virus (HSV) 2,3 and cytomegalovirus (CMV) 3 encephalitis. Furthermore, apoptotic cells can be observed in the diseased human heart during both active and chronic viral myocarditis 4 , and hepatocyte apoptosis is emerging as an important feature of liver injury in patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections [5][6][7][8][9][10] .The morphological and nuclear changes associated with apoptosis are typically caused by the sequential activation of a family of aspartate-specific cysteine proteases called caspases [11][12][13] (BOX 1). Caspase 3, the main executioner caspase, can be activated by the initiator caspase, caspase 8, following activation of cell-surface death receptors in the extrinsic apoptotic pathway (BOX 1 ; FIG. 1). Alternatively, the intrinsic apoptotic pathway can activate caspase 3 following release of pro-apoptotic factors from the mitochondria and activation of the initiator caspase, caspase 9 (BOX 1 ; FIG. 1). In some cell types (type I cells), activation of caspase 8 is sufficient for apoptosis. However, in other cell types (type II cells), apoptosis requires intrinsic apoptotic signalling, which can be activated directly or through extrinsic apoptotic signalling through the caspase 8-dependent cleavage of BCL-2 interacting domain death agonist (BID), a member of the BH3-only B-cell lymphoma protein 2 family (BOX 2 ; FIG. Correspondence to P.C. Penny.Clarke@uchsc.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 1). Caspase 3 can also be activated by granzyme B, a serine protease found in cytotoxic T lymphocytes (CTLs) (FIG. 1). Granzyme B can also cleave BID, forming the truncated protein gtBID and resulting in the activation of intrinsic apoptotic signalling 14 . Granzyme B and extrinsic apoptotic signalling constitute the two major components of CTL-induced cell death. B...

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Acute expression of hepatitis C core protein in adult mouse liver: Mitochondrial stress and apoptosis

Cited by 14 publications

References 32 publications

The Hepatitis C Virus Core Protein Contains a BH3 Domain That Regulates Apoptosis through Specific Interaction with Human Mcl-1

The Hepatitis C Virus Core Protein Contains a BH3 Domain That Regulates Apoptosis through Specific Interaction with Human Mcl-1

HPV-DNA Integration and Carcinogenesis: Putative Roles For Inflammation And Oxidative Stress

Apoptosis in animal models of virus-induced disease

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