Abstract:
:Human cytomegalovirus (HCMV) protein pUL38 has been shown to prevent premature cell death by antagonizing cellular stress responses; however, the underlying mechanism remains unknown. In this study, we identified the host protein ubiquitin-specific protease 24 (USP24) as an interaction partner of pUL38. Mutagenesis analysis of pUL38 revealed that amino acids TFV at positions 227 to 230 were critical for its interaction with USP24. Mutant pUL38 TFV/AAA protein did not bind to USP24 and failed to prevent cell death induced by pUL38-deficient HCMV infection. Knockdown of USP24 suppressed the cell death during pUL38-deficient HCMV infection, suggesting that pUL38 achieved its function by antagonizing the function of USP24. We investigated the cellular pathways regulated by USP24 that might be involved in the cell death phenotype by testing several small-molecule compounds known to have a protective effect during stress-induced cell death. The iron chelators ciclopirox olamine and Tiron specifically protected cells from pUL38-deficient HCMV infection-induced cell death, thus identifying deregulated iron homeostasis as a potential mechanism. Protein levels of nuclear receptor coactivator 4 (NCOA4) and lysosomal ferritin degradation, a process called ferritinophagy, were also regulated by pUL38 and USP24 during HCMV infection. Knockdown of USP24 decreased NCOA4 protein stability and ferritin heavy chain degradation in lysosomes. Blockage of ferritinophagy by genetic inhibition of NCOA4 or Atg5/Atg7 prevented pUL38-deficient HCMV infection-induced cell death. Overall, these results support the hypothesis that pUL38 binds to USP24 to reduce ferritinophagy, which may then protect cells from lysosome dysfunction-induced cell death.IMPORTANCE Premature cell death is considered a first line of defense against various pathogens. Human cytomegalovirus (HCMV) is a slow-replicating virus that encodes several cell death inhibitors, such as pUL36 and pUL37x1, which allow it to overcome both extrinsic and intrinsic mitochondrion-mediated apoptosis. We previously identified HCMV protein pUL38 as another virus-encoded cell death inhibitor. In this study, we demonstrated that pUL38 achieved its activity by interacting with and antagonizing the function of the host protein ubiquitin-specific protease 24 (USP24). pUL38 blocked USP24-mediated ferritin degradation in lysosomes, which could otherwise be detrimental to the lysosome and initiate cell death. These novel findings suggest that iron metabolism is finely tuned during HCMV infection to avoid cellular toxicity. The results also provide a solid basis for further investigations of the role of USP24 in regulating iron metabolism during infection and other diseases.
journal_name
J Viroljournal_title
Journal of virologyauthors
Sun Y,Bao Q,Xuan B,Xu W,Pan D,Li Q,Qian Zdoi
10.1128/JVI.00191-18subject
Has Abstractpub_date
2018-06-13 00:00:00issue
13eissn
0022-538Xissn
1098-5514pii
JVI.00191-18journal_volume
92pub_type
杂志文章abstract::The mechanism of action of hepatitis B virus (HBV) X protein in transcriptional transactivation and in tumorigenesis remains obscure. We have used the yeast two-hybrid system to identify a cellular protein that can interact with HBV X protein. This protein, designated X-associated protein 1 (XAP-1), is a human homolog...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.2.1107-1114.1995
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abstract::Hepatitis C virus (HCV) is a global challenge to public health. Several factors have been proven to be critical for HCV entry, including the newly identified claudin-1 (CLDN1). However, the mechanism of HCV entry is still obscure. Presently, among the 20 members of the claudin family identified in humans so far, CLDN1...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01457-07
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pub_type: 杂志文章
doi:10.1128/JVI.00396-09
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abstract::Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes simplex virus (HSV) infect...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01167-07
更新日期:2007-12-01 00:00:00
abstract::We sequenced the leftmost 2,640 base pairs of bacteriophage P4 DNA, thus completing the sequence of the 11,627-base-pair P4 genome. The newly sequenced region encodes three nonessential genes, which are called gop, beta, and cII (in order, from left to right). The gop gene product kills Escherichia coli when the beta ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.1.24-36.1990
更新日期:1990-01-01 00:00:00
abstract::The Epstein-Barr virus (EBV)-determined nuclear antigens EBNA 1, 2, 3, 4, and 6, regularly expressed in EBV-transformed lymphoblastoid cell lines, vary in size among viral strains. We have used this characteristic to trace the spread of the virus within seven families by using an approach called Ebnotyping. Among 33 e...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.10.4703-4708.1990
更新日期:1990-10-01 00:00:00
abstract::Efforts to induce broadly reactive immunity against human immunodeficiency virus type 1 (HIV-1) have been impaired by the extent of sequence variation exhibited by this lentivirus. Cytotoxic T lymphocytes (CTL) specific for other viruses such as influenza virus have been shown to mediate immunity against divergent vir...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.5.3145-3153.1994
更新日期:1994-05-01 00:00:00
abstract::Picornavirus genomes encode unique 5' noncoding regions (5' NCRs) which are approximately 600 to 1,300 nucleotides in length, contain multiple upstream AUG codons, and display the ability to form extensive secondary structures. A number of recent reports have shown that picornavirus 5' NCRs are able to facilitate cap-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.7.4364-4376.1992
更新日期:1992-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.6.3014-3023.2004
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pub_type: 杂志文章
doi:10.1128/JVI.00841-20
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abstract::Hemagglutinin (HA) of influenza virus must be activated by proteolysis before the virus can become infectious. Previous studies indicated that HA cleavage is driven by membrane-bound or extracellular serine proteases in the respiratory tract. However, there is still uncertainty as to which proteases are critical for a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00421-17
更新日期:2017-07-27 00:00:00
abstract::Arenaviruses are negative-strand RNA viruses that cause human diseases such as lymphocytic choriomeningitis, Bolivian hemorrhagic fever, and Lassa hemorrhagic fever. No licensed vaccines exist, and current treatment is limited to ribavirin. The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a mod...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02081-10
更新日期:2011-04-01 00:00:00
abstract::Nucleocytoplasmic shuttling and interaction with the cellular mRNA export factor UAP56 are prerequisites for the mRNA export activity of human cytomegalovirus (HCMV) pUL69. Although the murine cytomegalovirus homolog pM69 shuttles, it fails to export mRNAs due to its inability to recruit UAP56. However, chimeric prote...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00730-12
更新日期:2012-07-01 00:00:00
abstract::Skin fibroblast cultures were established from eight individuals. These cell cultures, together with WI-38 cells, were examined for susceptibility to transformation by SV40 virus. Four transformation-susceptible cell lines (TS), established from patients with Down's syndrome, were found to be three to four times more ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.5.3.293-298.1970
更新日期:1970-03-01 00:00:00
abstract::The temporal sequence of coronavirus plus-strand and minus-strand RNA synthesis was determined in 17CL1 cells infected with the A59 strain of mouse hepatitis virus (MHV). MHV-induced fusion was prevented by keeping the pH of the medium below pH 6.8. This had no effect on the MHV replication cycle, but gave 5- to 10-fo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.1.328-334.1986
更新日期:1986-01-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) gp41 plays a critical role in the viral fusion process, and its N- and C-terminal heptad repeat domains serve as important targets for developing anti-HIV-1 drugs, like T-20 (generic name, enfuvirtide; brand name, Fuzeon). Here, we conducted a yeast two-hybrid screening on a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00644-10
更新日期:2010-09-01 00:00:00
abstract::The adenovirus major late promoter (MLP) is active during both the early and late phases of infection. During the early phase the activity of the MLP is similar to those of the other early viral promoters, but during the late phase the rate of transcription from the MLP becomes much greater by comparison. We report he...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.1.51-60.1990
更新日期:1990-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.3.3.290-296.1969
更新日期:1969-03-01 00:00:00
abstract::The various strains of BK virus (BKV) exhibit a remarkable degree of heterogeneity in the transcriptional control region, which may affect the biological characteristics of a BKV strain. We describe the detection and sequencing of BKV control regions directly from urine samples and after propagation in cell culture. A...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.8.3864-3871.1990
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2006-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.11.3528-3535.1987
更新日期:1987-11-01 00:00:00
abstract::Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) transactivates EBV genes in latently infected B cells. We have shown that mitotic hyperphosphorylation of EBNA2 suppresses its ability to transactivate the latent membrane protein 1 (LMP1) promoter. In this follow-up study, we identify EBNA2 Ser243 as a phosphorylatio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.4.2045-2050.2006
更新日期:2006-02-01 00:00:00
abstract::Understanding the microbiome of ticks in Australia is of considerable interest given the ongoing debate over whether Lyme disease and its causative agent, the bacterium Borrelia burgdorferisensu lato, are present in Australia. The diversity of bacteria infecting Australian ticks has been studied using both culture- an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01358-18
更新日期:2019-01-17 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.30.1.76-83.1979
更新日期:1979-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.8.3935-3946.2006
更新日期:2006-04-01 00:00:00
abstract::Infection of neonatal mice with lymphocytic choriomeningitis virus (LCMV) strain Armstrong (ARM) results in a lifelong persistent infection. Viral variants (cytotoxic T lymphocyte [CTL] negative, persistence positive [CTL- P+]) can be isolated from the lymphoid tissues of such mice. Adult mice inoculated with these CT...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.11.7367-7373.1994
更新日期:1994-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.10.4499-4505.2001
更新日期:2001-05-01 00:00:00
abstract::The basis for the switch from CCR5 to CXCR4 coreceptor usage seen in approximately 50% of human immunodeficiency virus type 1 (HIV-1) subtype B-infected individuals as disease advances is not well understood. Among the reasons proposed are target cell limitation and better immune recognition of the CXCR4 (X4)-tropic c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00759-07
更新日期:2007-08-01 00:00:00
abstract:UNLABELLED:Following retrovirus entry, the viral capsid (CA) disassembles into its component capsid proteins. The rate of this uncoating process, which is regulated by CA-CA interactions and by the association of the capsid with host cell factors like cyclophilin A (CypA), can influence the efficiency of reverse transc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01388-14
更新日期:2014-09-01 00:00:00