Abstract:
:Multiple steps of the life cycle of hepatitis B virus (HBV) are known to be coupled to hepatic metabolism. However, the details of involvement of the hepatic metabolic milieu in HBV infection remain incompletely understood. Hepatic lipid metabolism is controlled by a complicated transcription factor network centered on retinoid X receptor alpha (RXRα). Here, we report that RXRα negatively regulates HBV infection at an early stage in cell cultures. The RXR-specific agonist bexarotene inhibits HBV in HepG2 cells expressing the sodium taurocholate cotransporting polypeptide (NTCP) (HepG2-NTCP), HepaRG cells, and primary Tupaia hepatocytes (PTHs); reducing RXRα expression significantly enhanced HBV infection in the cells. Transcriptome sequencing (RNA-seq) analysis of HepG2-NTCP cells with a disrupted RXRα gene revealed that reduced gene expression in arachidonic acid (AA)/eicosanoid biosynthesis pathways, including the AA synthases phospholipase A2 group IIA (PLA2G2A), is associated with increased HBV infection. Moreover, exogenous treatment of AA inhibits HBV infection in HepG2-NTCP cells. These data demonstrate that RXRα is an important cellular factor in modulating HBV infection and implicate the participation of AA/eicosanoid biosynthesis pathways in the regulation of HBV infection.IMPORTANCE Understanding how HBV infection is connected with hepatic lipid metabolism may provide new insights into virus infection and its pathogenesis. By a series of genetic studies in combination with transcriptome analysis and pharmacological assays, we here investigated the role of cellular retinoid X receptor alpha (RXRα), a crucial transcription factor for controlling hepatic lipid metabolism, in de novo HBV infection in cell cultures. We found that silencing of RXRα resulted in elevated HBV covalently closed circular DNA (cccDNA) formation and viral antigen production, while activation of RXRα reduced HBV infection efficiency. Our results also showed that silencing phospholipase A2 group IIA (PLA2G2A), a key enzyme of arachidonic acid (AA) synthases, enhanced HBV infection efficiency in HepG2-NTCP cells and that exogenous AA treatment reduced de novo HBV infection in the cells. These findings unveil RXRα as an important cellular factor in modulating HBV infection and may point to a new strategy for host-targeted therapies against HBV.
journal_name
J Viroljournal_title
Journal of virologyauthors
Song M,Sun Y,Tian J,He W,Xu G,Jing Z,Li Wdoi
10.1128/JVI.01771-17subject
Has Abstractpub_date
2018-03-28 00:00:00issue
8eissn
0022-538Xissn
1098-5514pii
JVI.01771-17journal_volume
92pub_type
杂志文章abstract::The complete DNA sequence of bovine adenovirus type 3 is reported here. The size of the genome is 34,446 bp in length with a G+C content of 54%. All the genes of the early and late regions are present in the expected locations of the genome. However, the late-region genes are organized into seven families, instead of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.2.1394-1402.1998
更新日期:1998-02-01 00:00:00
abstract::The retroviral restriction factor TRIMCyp, derived from the TRIM5 gene, blocks replication at a postentry step. TRIMCyp has so far been found in four species of Asian macaques, Macaca fascicularis, M. mulatta, M. nemestrina, and M. leonina. M. fascicularis is commonly used as a model for AIDS research, but TRIMCyp has...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00097-11
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.9.3579-3585.1989
更新日期:1989-09-01 00:00:00
abstract::An in vitro method which led to the transformation of hamster embryo fibroblasts after exposure to herpes simplex virus type 2 (HSV-2) inactivated with ultraviolet irradiation is described. The transformed cells (333-8-9) produced tumors when inoculated into newborn Syrian hamsters but not when injected into weanling ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.8.4.469-477.1971
更新日期:1971-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.1.2.362-367.1967
更新日期:1967-04-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.20.10437-10443.2002
更新日期:2002-10-01 00:00:00
abstract::The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.7.3979-3986.2005
更新日期:2005-04-01 00:00:00
abstract::Previous studies have suggested that the U(L)17 gene of herpes simplex virus type 1 (HSV-1) is essential for virus replication. In this study, viral mutants incorporating either a lacZ expression cassette in place of 1,490 bp of the 2,109-bp U(L)17 open reading frame [HSV-1(deltaU(L)17)] or a DNA oligomer containing a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.5.3779-3788.1998
更新日期:1998-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.23.1.117-125.1977
更新日期:1977-07-01 00:00:00
abstract::Subgroup J avian leukosis virus (ALV-J) isolate GDKP1202 was isolated from a 50-day-old local yellow commercial broiler in the Guangdong province of China in 2012. Here we report the complete genomic sequence of the GDKP1202 isolate, which caused high mortality, serious growth suppression, thymic atrophy, and liver en...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02009-12
更新日期:2012-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.4.2057-2061.2004
更新日期:2004-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03713-14
更新日期:2015-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.23.11137-11144.2000
更新日期:2000-12-01 00:00:00
abstract::Primate lentiviruses use chemokine coreceptors in addition to the CD4 receptor to initiate virus infection. Simian immunodeficiency virus (SIV) productively infects human cells expressing CD4 and the human allele of the chemokine coreceptor CCR-5 as efficiently as it infects macaque cells expressing human CD4, suggest...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.5.3932-3939.1997
更新日期:1997-05-01 00:00:00
abstract:UNLABELLED:MicroRNAs (miRNAs) are single-stranded small RNA molecules that regulate various cellular processes. miRNA 155 (miR-155) regulates various aspects of innate and adaptive immune responses and plays a key role in various viral infections and the resulting neuroinflammation. The present study evaluated the invo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02979-13
更新日期:2014-05-01 00:00:00
abstract::mRNA's homologous to the herpes simplex virus type 1 DNA restriction endonuclease fragment BamHI p, which contains the thymidine kinase gene, have been identified and mapped by hybrid-arrested translation and mRNA selection. Such mRNA's, when translated in vitro, directed the synthesis of polypeptides of apparent mole...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.2.593-605.1981
更新日期:1981-05-01 00:00:00
abstract:UNLABELLED:Identification and characterization of CD8(+) T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8(+) T cells have been only partially identified. In this study, we sought to identify CD8(+) T cells controlli...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00020-15
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03202-15
更新日期:2016-03-28 00:00:00
abstract:UNLABELLED:The role of NF-κB in influenza A virus (IAV) infection does not reveal a coherent picture, as pro- and also antiviral functions of this transcription factor have been described. To address this issue, we used clustered regularly interspaced short palindromic repeat with Cas9 (CRISPR-Cas9)-mediated genome eng...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00946-16
更新日期:2016-08-12 00:00:00
abstract::In polarized T cells, HIV-1 Gag localizes to a rear-end protrusion known as the uropod in a multimerization-dependent manner. Gag-laden uropods participate in formation of virological synapses, intercellular contact structures that play a key role in cell-to-cell HIV-1 transmission. Our previous observations suggest t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00040-13
更新日期:2013-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.2.241-249.1971
更新日期:1971-02-01 00:00:00
abstract::A gene encoding the large T antigen of polyomavirus was inserted into the baculovirus Autographa californica nuclear polyhedrosis virus so that gene expression was under the control of the strong, very late polyhedrin gene promoter. Significantly more large T antigen was produced in recombinant virus-infected insect c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.5.1712-1716.1987
更新日期:1987-05-01 00:00:00
abstract::Hepatitis B virus particles contain three related viral envelope proteins, the small, middle, and large S (surface) proteins. All three proteins contain the small S amino acid sequence at their carboxyl terminus. It is not clear which of these S proteins functions as the viral attachment protein, binding to a target c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.1981-1988.1989
更新日期:1989-05-01 00:00:00
abstract::Historically, the adenoviral E3 region was found to be nonessential for viral replication in vitro. In addition, adenoviruses whose genome was more than approximately 105% the size of the native genome were inefficiently packaged. These profound observations were used experimentally to insert transgenes into the adeno...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.9.5455-5465.2005
更新日期:2005-05-01 00:00:00
abstract::Ebola virus (EBOV) causes a lethal hemorrhagic fever for which there is no approved effective treatment or prevention strategy. EBOV VP35 is a virulence factor that blocks innate antiviral host responses, including the induction of and response to alpha/beta interferon. VP35 is also an RNA silencing suppressor (RSS). ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05741-11
更新日期:2012-03-01 00:00:00
abstract::A general theme that has emerged from studies of DNA tumor viruses is that otherwise unrelated oncoproteins encoded by these viruses often target the same important cellular factors. Major oncogenic determinants for human adenovirus type 9 (Ad9) and high-risk human papillomaviruses (HPV) are the E4-ORF1 and E6 oncopro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.20.9680-9693.2000
更新日期:2000-10-01 00:00:00
abstract::Interleukin-1 (IL-1) plays an important role in the inflammatory process. Some studies have demonstrated that IL-1 production was impaired in patients with chronic infections of hepatitis C virus (HCV), implying that IL-1 may play a role in viral clearance. Using an HCV subgenomic replicon cell line, we demonstrate th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.9.5493-5498.2003
更新日期:2003-05-01 00:00:00
abstract::HIV-1 Nef promotes virus spread and disease progression by altering host cell transport and signaling processes through interaction with multiple host cell proteins. The N-terminal region in HIV-1 Nef encompassing residues 12 to 39 has been implicated in many Nef activities, including disruption of CD4 T lymphocyte po...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01398-19
更新日期:2019-12-12 00:00:00
abstract::During infection, adenovirus-associated virus (AAV) undergoes microtubule-dependent retrograde transport as part of a program of vectorial transport of viral genome to the nucleus. A microtubule binding assay was used to evaluate the hypothesis that cytoplasmic dynein mediates AAV interaction with microtubules. Bindin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00481-06
更新日期:2006-08-01 00:00:00