Abstract:
:Lysine-specific demethylase 1 (LSD1) targets cellular proteins, including histone H3, p53, E2F, and Dnmt1, and is involved in the regulation of gene expression, DNA replication, the cell cycle, and the DNA damage response. LSD1 catalyzes demethylation of histone H3K9 associated with herpes simplex virus 1 (HSV-1) immediate early (IE) promoters and is necessary for IE gene expression, viral DNA replication, and reactivation from latency. We previously found that LSD1 associates with HSV-1 replication forks and replicating viral DNA, suggesting that it may play a direct role in viral replication or coupled processes. We investigated the effects of the LSD1 inhibitor SP-2509 on the HSV-1 life cycle. Unlike previously investigated LSD1 inhibitors tranylcypromine (TCP) and OG-L002, which covalently attach to the LSD1 cofactor flavin adenine dinucleotide (FAD) to inhibit demethylase activity, SP-2509 has previously been shown to inhibit LSD1 protein-protein interactions. We found that SP-2509 does not inhibit HSV-1 IE gene expression or transcription factor and RNA polymerase II (Pol II) association with viral DNA prior to the onset of replication. However, SP-2509 does inhibit viral DNA replication, late gene expression, and virus production. We used EdC labeling of nascent viral DNA to image aberrant viral replication compartments that form in the presence of SP-2509. Treatment resulted in the formation of small replication foci that colocalize with replication proteins but are defective for Pol II recruitment. Taken together, these data highlight a potential new role for LSD1 in the regulation of HSV-1 DNA replication and gene expression after the onset of DNA replication.IMPORTANCE Treatment of HSV-1-infected cells with SP-2509 blocked viral DNA replication, gene expression after the onset of DNA replication, and virus production. These data support a potential new role for LSD1 in the regulation of viral DNA replication and successive steps in the virus life cycle, and further highlight the promising potential to utilize LSD1 inhibition as an antiviral approach.
journal_name
J Viroljournal_title
Journal of virologyauthors
Harancher MR,Packard JE,Cowan SP,DeLuca NA,Dembowski JAdoi
10.1128/JVI.00974-20subject
Has Abstractpub_date
2020-09-15 00:00:00issue
19eissn
0022-538Xissn
1098-5514pii
JVI.00974-20journal_volume
94pub_type
杂志文章abstract::Although several virologic and immunologic factors associated with an increased risk of perinatal human immunodeficiency virus type 1 (HIV-1) transmission have been described, the mechanism of mother-to-child transmission is still unclear. More specifically, the question of whether selective pressures influence the tr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.5.3050-3057.2003
更新日期:2003-03-01 00:00:00
abstract::Acute measles in children can be prevented by immunization with the live attenuated measles vaccine virus. Although immunization is able to induce CD4 and CD8 T cells as well as neutralizing antibodies, only the latter have been correlated with protective immunity. CD8 T cells, however, have been documented to be impo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00160-07
更新日期:2007-08-01 00:00:00
abstract::A deletion mutant of severe acute respiratory syndrome coronavirus (SARS-CoV) has been engineered by deleting the structural E gene in an infectious cDNA clone that was constructed as a bacterial artificial chromosome (BAC). The recombinant virus lacking the E gene (rSARS-CoV-DeltaE) was rescued in Vero E6 cells. The ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01467-06
更新日期:2007-02-01 00:00:00
abstract::Vaccinia virus assembles two distinct lipoprotein membranes. The primary membrane contains nonglycosylated proteins, appears as crescents in the cytoplasm, and delimits immature and mature intracellular virions. The secondary or wrapping membrane contains glycoproteins, is derived from virus-modified trans-Golgi or en...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.21.11754-11766.2003
更新日期:2003-11-01 00:00:00
abstract::In this work we show evidence of mother-to-offspring transmission in a transgenic mouse line expressing bovine PrP (boTg) experimentally infected by intracerebral administration of bovine spongiform encephalopathy (BSE) prions. PrP(res) was detected in brains of newborns from infected mothers only when mating was allo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.13.8665-8668.2005
更新日期:2005-07-01 00:00:00
abstract::Human T-cell leukemia virus type 1 (HTLV-1) establishes a persistent infection in the host despite a vigorous virus-specific immune response. Here we demonstrate that an HTLV-1-encoded protein, p12(I), resides in the endoplasmic reticulum (ER) and Golgi and physically binds to the free human major histocompatibility c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.13.6086-6094.2001
更新日期:2001-07-01 00:00:00
abstract::The family Anelloviridae includes human and animal torque teno viruses (TTVs) with extensive genetic diversity. The antigenic diversity among anelloviruses has never been assessed. Using torque teno sus virus (TTSuV) as a model, we describe here the first investigation of the antigenic relationships among different an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00176-12
更新日期:2012-10-01 00:00:00
abstract::The nonstructural 4B (NS4B) protein of hepatitis C virus (HCV) plays a central role in the formation of the HCV replication complex. To gain insight into the role of charged residues for NS4B function in HCV RNA replication, alanine substitutions were engineered in place of 28 charged residues residing in the N- and C...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00858-11
更新日期:2011-08-01 00:00:00
abstract::Passage of native classical swine fever virus (CSFV) in cultured swine kidney cells (SK6 cells) selects virus variants that attach to the surface of cells by interaction with membrane-associated heparan sulfate (HS). A Ser-to-Arg change in the C terminus of envelope glycoprotein E(rns) (amino acid 476 in the open read...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.20.9585-9595.2001
更新日期:2001-10-01 00:00:00
abstract::At least four members of the integrin family of receptors, alphaVbeta1, alphaVbeta3, alphaVbeta6, and alphaVbeta8, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. Our investigators have recently shown that the efficiency of receptor usage appears to be related to the viral serotype ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.18.9773-9781.2004
更新日期:2004-09-01 00:00:00
abstract::Influenza viruses unable to express NS1 protein (delNS1) replicate poorly and induce large amounts of interferon (IFN). They are therefore considered candidate viruses for live-attenuated influenza vaccines. Their attenuated replication is generally assumed to result from the inability to counter the antiviral host re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01725-12
更新日期:2012-11-01 00:00:00
abstract::Recent reports suggest that human genogroup II genotype 17 (GII.17) noroviruses are increasing in prevalence. We analyzed the evolutionary changes of three GII.17 capsid protruding (P) domains. We found that the GII.17 P domains had little cross-reactivity with antisera raised against the dominant GII.4 strains. X-ray...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03119-15
更新日期:2015-12-23 00:00:00
abstract::Early sensing of viral components or infection-induced tissue damage is a prerequisite for the successful control of pathogenic viruses by the host innate immune system. Recent results from our laboratory show how immune cells use the DNA-sensing machinery to detect intracellular damage generated early during infectio...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.01081-16
更新日期:2017-06-26 00:00:00
abstract::The adaptive immune system generates CD8 cytotoxic T lymphocytes (CTLs) as a major component of the protective response against viruses. Knowledge regarding the nature of the peptide sequences presented by HLA class I molecules and recognized by CTLs is thus important for understanding host-pathogen interactions. In t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.24.13399-13408.2004
更新日期:2004-12-01 00:00:00
abstract::Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective im...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.13.6669-6677.2002
更新日期:2002-07-01 00:00:00
abstract::Betanodaviruses, the causal agents of viral nervous necrosis in marine fish, have bipartite positive-sense RNAs as genomes. The larger genomic segment, RNA1 (3.1 kb), encodes an RNA-dependent RNA polymerase, and the smaller genomic segment, RNA2 (1.4 kb), codes for the coat protein. Betanodaviruses have marked host sp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.3.1256-1262.2004
更新日期:2004-02-01 00:00:00
abstract:UNLABELLED:Virus-like particles (VLPs) built on the Newcastle disease virus (NDV) core proteins, NP and M, and containing two chimeric proteins, F/F and H/G, composed of respiratory syncytial virus (RSV) fusion protein (F) and glycoprotein (G) ectodomains fused to the transmembrane and cytoplasmic domains of the NDV F ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00384-15
更新日期:2015-07-01 00:00:00
abstract::Bacteriophage PRD1 contains DNA, 17 proteins, and lipid. The assembly pathway involves the formation of empty particles that contain lipid and all of the proteins of mature virions, with the possible exception of one. The major and minor capsid proteins, P3 and P5, occur as soluble multimers before they appear in the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.3.1021-1030.1982
更新日期:1982-12-01 00:00:00
abstract::Heating oncornavirus RNAs at temperatures insufficient for complete denaturation results in forms migrating between the native form (vRNA) and the completely denatured form (vRNA) after gel electrophoresis. Intermediate forms from Rous sarcoma virus or murine leukemia virus were isolated after heating of vRNA's at 58 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.19.3.810-819.1976
更新日期:1976-09-01 00:00:00
abstract:UNLABELLED:Inhibitor-of-apoptosis (IAP) proteins are key regulators of the innate antiviral response by virtue of their capacity to respond to signals affecting cell survival. In insects, wherein the host IAP provides a primary restriction to apoptosis, diverse viruses trigger rapid IAP depletion that initiates caspase...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03659-14
更新日期:2015-04-01 00:00:00
abstract::To assess the RNA helicase activity of hepatitis C virus (HCV) nonstructural protein 3 (NS3), a polypeptide encompassing amino acids 1175 to 1657, which cover only the putative helicase domain, was expressed in Escherichia coli by a pET expression vector. The protein was purified to near homogeneity and assayed for RN...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.12.8477-8484.1996
更新日期:1996-12-01 00:00:00
abstract::The yeast retrotransposon Ty1 resembles retroviruses in a number of important respects but also shows several fundamental differences from them. We now report that, as in retroviruses, the genomic RNA in Ty1 virus-like particles is dimeric. The Ty1 dimers also resemble retroviral dimers in that they are stabilized dur...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.22.10819-10821.2000
更新日期:2000-11-01 00:00:00
abstract::A number of cDNA clones complementary to measles virus mRNA and 50S genome RNA have been generated. These clones have been mapped by restriction enzyme analysis and were subsequently sequenced by the method of Maxam and Gilbert (A. M. Maxam and W. Gilbert, Methods Enzymol. 65:499-560, 1980). Computer analysis of these...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.54.1.186-193.1985
更新日期:1985-04-01 00:00:00
abstract::Recombinant adeno-associated virus (rAAV) vectors have been shown to be useful for efficient gene delivery to a variety of dividing and nondividing cells. Mechanisms responsible for the long-term, persistent expression of the rAAV transgene are not well understood. In this study we investigated the kinetics of rAAV-me...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.8.3555-3565.2000
更新日期:2000-04-01 00:00:00
abstract::During Epstein-Barr virus (EBV) latent infection of B lymphocytes in vitro, six viral nuclear antigens (EBNAs) are expressed from one of two promoters, Cp or Wp, whose activities have previously been shown to be mutually exclusive in established lymphoblastoid cell lines. Initially after infection, the EBNA genes are ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.12.9134-9142.1997
更新日期:1997-12-01 00:00:00
abstract::Crucial steps in high-risk human papillomavirus (HR-HPV)-related carcinogenesis are the integration of HR-HPV into the host genome and loss of viral episomes. The mechanisms that promote cervical neoplastic progression are, however, not clearly understood. During HR-HPV infection, the HPV E5 protein is expressed in pr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02114-10
更新日期:2011-05-01 00:00:00
abstract::The retroviral Gag protein plays the central role in the assembly process and can form membrane-enclosed, virus-like particles in the absence of any other viral products. These particles are similar to authentic virions in density and size. Three small domains of the human immunodeficiency virus type 1 (HIV-1) Gag pro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.6.4667-4677.1998
更新日期:1998-06-01 00:00:00
abstract::In polarized epithelial cells, the vesicular stomatitis virus glycoprotein is segregated to the basolateral plasma membrane, where budding of the virus takes place. We have generated recombinant viruses expressing mutant glycoproteins without the basolateral-membrane-targeting signal in the cytoplasmic domain. Though ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.8.4103-4107.2002
更新日期:2002-04-01 00:00:00
abstract::The phenomenon of prion strains with distinct biological characteristics has been hypothesized to be involved in the structural diversity of abnormal prion protein (PrP(Sc)). However, the molecular basis of the transmission of strain properties remains poorly understood. Real-time quaking-induced conversion (RT-QUIC) ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00585-14
更新日期:2014-10-01 00:00:00
abstract::We have studied the functions of the intracellular RNAs of mouse mammary tumor virus (MMTV) by purification and translation in vitro. Two major size classes of MMTV RNA, 35S and 24S RNA, were isolated from MMTV-infected rat (XC) cells and cultured mammary tumor cells by preparative hybridization of whole cell or polya...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.1.207-218.1981
更新日期:1981-07-01 00:00:00