Abstract:
:CTCF and the cohesin complex modify chromatin by binding to DNA and interacting with each other and with other cellular proteins. Both proteins regulate transcription by a variety of local effects on transcription and by long-range topological effects. CTCF and cohesin also bind to herpesvirus genomes at specific sites and regulate viral transcription during latent and lytic cycles of replication. Kaposi's sarcoma-associated herpesvirus (KSHV) transcription is regulated by CTCF and cohesin, with both proteins previously reported to act as restrictive factors for lytic cycle transcription and virion production. In this study, we examined the interdependence of CTCF and cohesin binding to the KSHV genome. Chromatin immunoprecipitation sequencing (ChIP-seq) analyses revealed that cohesin binding to the KSHV genome is highly CTCF dependent, whereas CTCF binding does not require cohesin. Furthermore, depletion of CTCF leads to the almost complete dissociation of cohesin from sites at which they colocalize. Thus, previous studies that examined the effects of CTCF depletion actually represent the concomitant depletion of both CTCF and cohesin components. Analysis of the effects of single and combined depletion indicates that CTCF primarily activates KSHV lytic transcription, whereas cohesin has primarily inhibitory effects. Furthermore, CTCF or cohesin depletion was found to have regulatory effects on cellular gene expression relevant for the control of viral infection, with both proteins potentially facilitating the expression of multiple genes important in the innate immune response to viruses. Thus, CTCF and cohesin have both positive and negative effects on KSHV lytic replication as well as effects on the host cell that enhance antiviral defenses.IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to Kaposi's sarcoma and several lymphoproliferative diseases. KSHV, like other herpesviruses, intermittently reactivates from latency and enters a lytic cycle in which numerous lytic mRNAs and proteins are produced, culminating in infectious virion production. These lytic proteins may also contribute to tumorigenesis. Reactivation from latency is controlled by processes that restrict or activate the transcription of KSHV lytic genes. KSHV gene expression is modulated by binding of the host cell proteins CTCF and cohesin complex to the KSHV genome. These proteins bind to and modulate the conformation of chromatin, thereby regulating transcription. We have analyzed the interdependence of binding of CTCF and cohesin and demonstrate that while CTCF is required for cohesin binding to KSHV, they have very distinct effects, with cohesin primarily restricting KSHV lytic transcription. Furthermore, we show that cohesin and CTCF also exert effects on the host cell that promote antiviral defenses.
journal_name
J Viroljournal_title
Journal of virologyauthors
Li D,Mosbruger T,Verma D,Swaminathan Sdoi
10.1128/JVI.01279-19subject
Has Abstractpub_date
2020-01-06 00:00:00issue
2eissn
0022-538Xissn
1098-5514pii
JVI.01279-19journal_volume
94pub_type
杂志文章abstract::Neonatal infection of most mouse strains with lymphocytic choriomeningitis virus (LCMV) leads to a life-long persistent infection characterized by high virus loads in the central nervous system (CNS) in the absence of inflammation and tissue destruction. These mice, however, exhibit impaired learning and memory. The o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00795-06
更新日期:2006-09-01 00:00:00
abstract::Epstein-Barr virus (EBV) in vivo is known to establish persistent infection in resting, circulating memory B cells and to productively replicate in plasma cells. Until now, the molecular mechanism of how EBV switches from latency to lytic replication in vivo was not known. Here, we report that the plasma cell differen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01055-07
更新日期:2007-12-01 00:00:00
abstract::Avian erythroblastosis virus (AEV) RNA rescued from nonproducer cells by superinfection with a helper virus is translated into three polypeptides in the messenger-dependent rabbit reticulocyte lysate. A 75,000 molecular weight polypeptide (P75AEV) is synthesized from 28S RNA and is encoded by the 5' section of the AEV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.34.1.280-284.1980
更新日期:1980-04-01 00:00:00
abstract::The replication of the single-stranded DNA (ssDNA) of parvovirus LuIII was studied in synchronized HeLa cells. After infection of the cells in early S phase, synthesis of a replicative form (RF) DNA became detectable as early as 9 h postinfection, i.e., after display of the cellular helper function(s) indispensable fo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.17.3.841-853.1976
更新日期:1976-03-01 00:00:00
abstract::Superinfection of Corynebacterium diphtheriae C7(beta) by heteroimmune phage gamma is productive, whereas superinfection by gamma-bin mutants is for the most part nonproductive. Exclusion of gamma-bin phage occurred after its DNA had penetrated and was partially expressed in the heteroimmune lysogen. All of the infect...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.2.526-532.1980
更新日期:1980-11-01 00:00:00
abstract::The ectopic overexpression of Bcl-2 restricts both influenza A virus-induced apoptosis and influenza A virus replication in MDCK cells, thus suggesting a role for Bcl-2 family members during infection. Here we report that influenza A virus cannot establish an apoptotic response without functional Bax, a downstream tar...
journal_title:Journal of virology
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doi:10.1128/JVI.02672-08
更新日期:2009-08-01 00:00:00
abstract::An E1-E3-deleted recombinant adenovirus vector expressing the hybrid protein TetR-KRAB has been produced. In this virus, AdTG9562, the E2 transcription is regulated by TetR-KRAB and tetO sequences inserted in cis. In the absence of tetracycline, a strong reduction in E2A gene expression, viral DNA replication, and lat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.4.3307-3311.1997
更新日期:1997-04-01 00:00:00
abstract:UNLABELLED:One of the first lines of host defense against many viruses in vertebrates is the innate immune system, which detects pathogen-associated molecular patterns (PAMPs) using pathogen recognition receptors (PRR). The dynamic interactions between pathogens and hosts create, in some cases, species-specific relatio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03576-14
更新日期:2015-03-01 00:00:00
abstract::Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01689-12
更新日期:2012-12-01 00:00:00
abstract::Adenovirus types 5 and 3 (Ad5 and Ad3), two human adenovirus serotypes of evolutionarily divergent subgroups, show very different levels of E1A gene expression early after infection of permissive cells. Since adenovirus E1A gene expression is known to be transcriptionally autoregulated, we have investigated the differ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.4.1833-1838.1989
更新日期:1989-04-01 00:00:00
abstract::Two major DNA variants have been isolated from serially propagated stocks of the WR strain of vaccinia virus. Restriction enzyme mapping of the two variants with HindIII, AvaI, XhoI, SstII, and SmaI revealed a 6.3-megadalton deletion in the smaller DNA variant. The deletion was mapped at ca. 6.8 megadaltons in from th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.3.1000-1010.1981
更新日期:1981-03-01 00:00:00
abstract::Analysis of large and small plaque mutants of simian virus 40 using antisera prepared against each has revealed quantitative and possibly qualitative antigenic differences for each plaque type. A sensitive micro radioisotope precipitation test permitted evaluation of immunochemical similarities and differences of caps...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.3.1.17-24.1969
更新日期:1969-01-01 00:00:00
abstract::The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates the HTLV-1 long terminal repeat and key regulatory proteins involved in inflammation, activation, and proliferation and may induce cell transformation. Tax is also the immunodominant target antigen for cytotoxic T cells in HTLV-1 infection. We found...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.22.11106-11115.2001
更新日期:2001-11-01 00:00:00
abstract::Rhesus monkey rhadinovirus (RRV) is a close relative of Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8). RRV serves as an in vitro and an in vivo model for KSHV, and the mapping of its transcription program during lytic replication is significant since it represents de novo infection in the absence...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.19.9819-9831.2002
更新日期:2002-10-01 00:00:00
abstract::Cellular inhibitor of apoptosis protein 2 (cIAP2) is a potent suppressor of apoptotic cell death. We have shown previously that cIAP2 is involved in the tumor necrosis factor alpha (TNF-α)-induced anti-hepatitis B virus (HBV) response; however, the mechanism for this antiviral effect remains unclear. In the present st...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00879-11
更新日期:2011-11-01 00:00:00
abstract::In vitro translation of the three single-stranded RNAs transcribed in vitro by bacteriophage phi 6 RNA polymerase revealed that the large RNA codes for phage proteins P1, P2, P4, and P7, the medium RNA codes for P3, P6, and P10, and the smaller RNA for P5, P8, and P9. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.35.1.249-251.1980
更新日期:1980-07-01 00:00:00
abstract::The influenza A virus nucleoprotein (NP) is a multifunctional polypeptide which plays a pivotal role in virus replication. To get information on the domains and specific residues involved in the different NP activities, we describe here the preparation and characterization of 20 influenza A virus mutant NPs. The mutat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.2.1186-1194.1999
更新日期:1999-02-01 00:00:00
abstract::Previous results have indicated that Rous sarcoma virus env gene expression is specifically inhibited by antisense RNA (L.-J. Chang and C. M. Stoltzfus, Mol. Cell. Biol. 5:2341-2348, 1985). In this study, we compare the extents of inhibition by antisense RNA derived from different parts of the Rous sarcoma virus genom...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.3.921-924.1987
更新日期:1987-03-01 00:00:00
abstract::Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infants and the elderly, but no safe and effective RSV vaccine is yet available. For reasons that are not well understood, RSV is only weakly immunogenic, and reinfection occurs throughout life. This has complicated the sea...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.3.1130-1139.2006
更新日期:2006-02-01 00:00:00
abstract::The herpes simplex virus type 1 (HSV-1) alkaline nuclease, encoded by the UL12 gene, plays an important role in HSV-1 replication, as a UL12 null mutant displays a severe growth defect. The HSV-1 alkaline exonuclease UL12 interacts with the viral single-stranded DNA binding protein ICP8 and promotes strand exchange in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01506-10
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abstract::Resistance to human immunodeficiency virus type 1 protease (HIV PR) inhibitors results primarily from the selection of multiple mutations in the protease region. Because many of these mutations are selected for the ability to decrease inhibitor binding in the active site, they also affect substrate binding and potenti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.3.1359-1368.2002
更新日期:2002-02-01 00:00:00
abstract::Murine gammaherpesvirus 68 (gammaHV68) provides an important experimental model for understanding mechanisms of immune control of the latent human gammaherpesviruses. Antiviral CD8 T cells play a key role throughout three separate phases of the infection: clearance of lytic virus, control of the latency amplification ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02229-09
更新日期:2010-03-01 00:00:00
abstract::Humoral immune responses to influenza virus vaccines in elderly individuals are poorly adapted toward new antigenically drifted influenza virus strains. Instead, older individuals respond in an original antigenic sin fashion and produce much more cross-reactive but less potent antibodies. Here, we investigated four in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01185-20
更新日期:2020-11-09 00:00:00
abstract::Marek's disease herpesvirus A antigen (MDHV-A) was identified as a 61,000- to 65,000-dalton glycoprotein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after immunoprecipitation from the culture medium of both [35S]methionine- and [14C]glucosamine-labeled infected cells by specific rabbit serum directed ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.45.3.1228-1234.1983
更新日期:1983-03-01 00:00:00
abstract::Coxsackievirus B3 (CVB3) is known to infect stem cells in the neonatal central nervous system. Here, we evaluated the effects of CVB3 infection on the major source and repository of stem cells, the bone marrow (BM). Viral genome was detectable in BM within 24 h of infection, and productive infection of BM cells was ev...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03004-12
更新日期:2013-03-01 00:00:00
abstract::Flaviviruses are enveloped viruses which accumulate in cellular vacuoles prior to release. The membrane of cell-associated virus contains the proteins pre-M and E. During release of virus the pre-M protein is cleaved, and only its carboxy-terminal segment remains associated with the virus as M protein. Studies of the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.6.2521-2526.1989
更新日期:1989-06-01 00:00:00
abstract::The Kaposi's sarcoma-associated herpesvirus nuclear egress complex is composed of two proteins, ORF67 and ORF69. In this study, we have recapitulated the KSHV complex by coexpression of these two proteins in insect cells using expression from recombinant baculoviruses. The proteins form a complex at the nuclear membra...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05988-11
更新日期:2012-01-01 00:00:00
abstract::Interleukin-1 receptor antagonist (IL-1ra) gene polymorphisms in 83 human immunodeficiency virus (HIV)-seropositive women were evaluated. Fourteen of the subjects (16.9%) were homozygous for IL-1ra allele 2 (IL-1RN*2). These women had a lower median level of HIV RNA than did women homozygous for allele 1 (IL-1RN*1) (P...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.13.6242-6244.2001
更新日期:2001-07-01 00:00:00
abstract::Lentiviruses have long been considered host-specific pathogens, but several recent observations demonstrated their capacity to conquer new hosts from different species, genera, and families. From these cross-species infections emerged new animal and human infectious diseases. The successful colonization and adaptation...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.11.6430-6437.2003
更新日期:2003-06-01 00:00:00
abstract::Small amounts of infectious simian virus 40 (SV40) were recovered from parental cultures of SV40-transformed human embryonic lung (WI38 Va13A) cells, from 12 primary clones, from 17 secondary clones, and from 18 tertiary clones. The cloning experiments demonstrated that the capacity for spontaneous virus production is...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.8.4.430-436.1971
更新日期:1971-10-01 00:00:00