Abstract:
:Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is a 1,162-amino-acid protein that mediates episome persistence of viral genomes. LANA binds the KSHV terminal-repeat (TR) sequence through its carboxy-terminal domain to mediate DNA replication. LANA simultaneously binds mitotic chromosomes and TR DNA to segregate virus genomes to daughter cell nuclei. Amino-terminal LANA attaches to chromosomes by binding histones H2A/H2B, and carboxy-terminal LANA contributes to mitotic-chromosome binding. Although amino- and carboxy-terminal LANA are essential for episome persistence, they are not sufficient, since deletion of all internal LANA sequence renders LANA highly deficient for episome maintenance. Internal LANA sequence upstream of the internal repeat elements contributes to episome segregation and persistence. Here, we investigate this region with a panel of LANA deletion mutants. Mutants retained the ability to associate with mitotic chromosomes and bind TR DNA. In contrast to prior results, deletion of most of this sequence did not reduce LANA's ability to mediate DNA replication. Deletions of upstream sequence within the region compromised segregation of TR DNA to daughter cells, as assessed by retention of green fluorescent protein (GFP) expression from a replication-deficient TR plasmid. However, deletion of this upstream sequence did not reduce episome maintenance. In contrast, deletions that included an 80-amino-acid sequence immediately downstream resulted in highly deficient episome persistence. LANA with this downstream sequence deleted maintained the ability to replicate and segregate TR DNA, suggesting a unique role for the residues. Therefore, this work identifies adjacent LANA regions with distinct roles in episome segregation and persistence.IMPORTANCE KSHV LANA mediates episomal persistence of viral genomes. LANA binds the KSHV terminal-repeat (TR) sequence to mediate DNA replication and tethers KSHV DNA to mitotic chromosomes to segregate genomes to daughter cell nuclei. Here, we investigate LANA sequence upstream of the internal repeat elements that contributes to episome segregation and persistence. Mutants with deletions within this sequence maintained the ability to bind mitotic chromosomes or bind and replicate TR DNA. Deletion of upstream sequence within the region reduced segregation of TR DNA to daughter cells, but not episome maintenance. In contrast, mutants with deletions of 80 amino acids immediately downstream were highly deficient for episome persistence yet maintained the ability to replicate and segregate TR DNA, the two principal components of episome persistence, suggesting another role for the residues. In summary, this work identifies adjacent LANA sequence with distinct roles in episome segregation and persistence.
journal_name
J Viroljournal_title
Journal of virologyauthors
Juillard F,De León Vázquez E,Tan M,Li S,Kaye KMdoi
10.1128/JVI.02158-18subject
Has Abstractpub_date
2019-03-05 00:00:00issue
6eissn
0022-538Xissn
1098-5514pii
JVI.02158-18journal_volume
93pub_type
杂志文章abstract::Vesicular stomatitis virus (VSV) vectors that express heterologous antigens have shown promise as vaccines in preclinical studies. The efficacy of VSV-based vaccines can be improved by engineering vectors that enhance innate immune responses. We previously generated a VSV vaccine vector that incorporates two enhancing...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02898-13
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abstract::In an earlier study on minus-strand DNA synthesis catalyzed by murine leukemia virus reverse transcriptase, we described a prominent pause site near the polypurine tract (J. Guo, W. Wu, Z. Y. Yuan, K. Post, R. J. Crouch, and J. G . Levin, Biochemistry 34:5018-5029, 1995). We now report that pausing at this site is due...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.10.7132-7142.1996
更新日期:1996-10-01 00:00:00
abstract::Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01548-18
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abstract::Sections of normal and diseased brain and kidney tissues were screened for the presence of JC virus (JCV) DNA by using the polymerase chain reaction. As expected, all samples obtained from patients with progressive multifocal leukoencephalopathy (PML) tested positive when multiple JCV-specific primer and probe combina...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.10.5726-5734.1992
更新日期:1992-10-01 00:00:00
abstract::The E3 complex transcription unit of adenovirus encodes four major mRNAs (a, c, f, and h) and two minor (d and e) mRNAs with overlapping exons, alternative splice sites, and two polyadenylation sites, termed E3A (upstream) and E3B (downstream). mRNAs a and d use the E3A polyadenylation site, and mRNAs c, e, f, and h u...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.10.5914-5923.1992
更新日期:1992-10-01 00:00:00
abstract::Simian varicella virus (SVV) and varicella-zoster virus (VZV) are closely related alphaherpesviruses that cause varicella (chickenpox) in nonhuman primates and humans, respectively. After resolution of the primary disease, SVV and VZV establish latent infection of neural ganglia and may later reactivate to cause a sec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00407-07
更新日期:2007-08-01 00:00:00
abstract::Using real-time fluorescence PCR, we quantitated the numbers of copies of latent varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) genomes in 15 human trigeminal ganglia. Eight (53%) and 1 (7%) of 15 ganglia were PCR positive for HSV-1 or -2 glycoprotein G genes, with means of 2,9...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.12.10514-10518.1999
更新日期:1999-12-01 00:00:00
abstract::The DA strain of Theiler's murine encephalomyelitis virus persists in the white matter of the spinal cords of susceptible mice. Previous results showed that the difference in susceptibility to viral persistence between the susceptible SJL/J strain and the resistant B10.S strain was due to multiple non-H-2 loci. The re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.11.5807-5812.2002
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abstract::Interaction of the C-terminal domains of Sendai virus (SeV) P and N proteins is crucial for RNA synthesis by correctly positioning the polymerase complex (L+P) onto the nucleocapsid (N/RNA). To better understand this mechanism within the paramyxovirus family, we have studied the complex formed by the SeV C-terminal do...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00338-07
更新日期:2007-07-01 00:00:00
abstract::Group I host range (hr) mutants of adenovirus type 5 are unable to transform rat embryo or rat embryo brain cells but induce an abnormal transformation of baby rat kidney cells. We established several transformed rat kidney cell lines and characterized them with respect to the transformed phenotype and the structure o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.41.2.674-685.1982
更新日期:1982-02-01 00:00:00
abstract::Retroviral Gag proteins direct the assembly and release of virus particles from the plasma membrane. The budding machinery consists of three small domains, the M (membrane-binding), I (interaction), and L (late or "pinching-off") domains. In addition, Gag proteins contain sequences that control particle size. For Rous...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.14.6527-6536.2001
更新日期:2001-07-01 00:00:00
abstract::The herpes simplex virus type 1 latency-associated transcript (LAT) inhibits apoptosis. We demonstrate here that LAT influences the accumulation of the Bcl-x(L) transcript versus the Bcl-x(S) transcript in Neuro-2A cells. Bcl-x(L) encodes an antiapoptotic protein, whereas Bcl-x(S) encodes a proapoptotic protein. Promo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.19.10714-10718.2003
更新日期:2003-10-01 00:00:00
abstract::Hepatitis C virus (HCV) replication in infected patients produces large and diverse viral populations, which give rise to drug-resistant and immune escape variants. Here, we analyzed HCV populations during transmission and diversification in longitudinal and cross-sectional samples using 454/Roche pyrosequencing, in t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02271-09
更新日期:2010-06-01 00:00:00
abstract::The internal structural proteins of retroviruses are proteolytically processed from the Gag polyprotein, which alone is able to assemble into virus-like particles when expressed in cells. All Gag proteins contain domains corresponding to the three structural proteins MA, CA, and NC. We have expressed the CA and NC dom...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.10.6487-6497.1995
更新日期:1995-10-01 00:00:00
abstract::Whether a genetic informational nucleic acid is required for the infectivity of transmissible spongiform encephalopathies is central to the debate about the infectious agent. Here we report that an infectious prion formed with bacterially expressed recombinant prion protein plus synthetic polyriboadenylic acid and syn...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06216-11
更新日期:2012-02-01 00:00:00
abstract::Normal levels of the hypermodified pyrimidine, alpha-putrescinylthymine, which is formed from hydhydroxymethyluracil at the polynucleotide level (Maltman et al., J. Virol. 34:354-359, 1984), are not required in bacteriophage luminal diameterW-14 DNA for the DNA to serve as a replicative template in luminal diameterW-1...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.52.3.1036-1038.1984
更新日期:1984-12-01 00:00:00
abstract::Mutations at amino acids 143, 148, and 155 in HIV-1 integrase (IN) define primary resistance pathways in subjects failing raltegravir (RAL)-containing treatments. Although each pathway appears to be genetically distinct, shifts in the predominant resistant virus population have been reported under continued drug press...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06618-11
更新日期:2012-07-01 00:00:00
abstract::In infected cells, hepatitis C virus (HCV) induces the formation of membrane alterations referred to as membranous webs, which are sites of RNA replication. In addition, HCV RNA replication also occurs in smaller membrane structures that are associated with the endoplasmic reticulum. However, cellular mechanisms invol...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01190-09
更新日期:2010-01-01 00:00:00
abstract::To gain insight into the cellular regulation of bovine leukemia virus (BLV) trans activation, a lambda-gt11 cDNA library was constructed with mRNA isolated from a BLV-induced tumor and the recombinant proteins were screened with an oligonucleotide corresponding to the tax activation-responsive element (TAR). Two clone...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.2.766-772.1992
更新日期:1992-02-01 00:00:00
abstract::The nucleotide sequences of several sites of recombination between adenovirus DNA and hamster, mouse, or human cell DNAs were determined. These sites of recombination had been cloned from adenovirus type 2 (Ad2)- or type 12 (Ad12)-transformed cells, from Ad12-induced tumor cells, or from a symmetric recombinant betwee...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.2.344-353.1987
更新日期:1987-02-01 00:00:00
abstract::During the late phase of simian virus 40 infections of CV1 cells, the relative ratios of the spliced to the unspliced RNA molecules of the 19S family were measured. In the cytoplasm, unspliced 19S RNA represented between 1 and 2% of spliced 19S RNA. This ratio could be altered by the use of different methods of RNA ex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.2.595-600.1980
更新日期:1980-11-01 00:00:00
abstract::It has been reported that gene expression directed by the long terminal repeat of Rous sarcoma virus (RSV) is trans activated by a protein encoded in an alternate reading frame within the RSV gag gene (S. Broome and W. Gilbert, Cell 40:537-546, 1985). We have made specific mutations to test the role of the putative tr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.11.4003-4008.1988
更新日期:1988-11-01 00:00:00
abstract::African swine fever virus (ASFV) multigene family 360 and 530 (MGF360/530) genes affect viral growth in macrophage cell cultures and virulence in pigs (L. Zsak, Z. Lu, T. G. Burrage, J. G. Neilan, G. F. Kutish, D. M. Moore, and D. L. Rock, J. Virol. 75:3066-3076, 2001). The mechanism by which these novel genes affect ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.4.1858-1864.2004
更新日期:2004-02-01 00:00:00
abstract::We have analyzed the structure of rubella virus proteins labeled metabolically with [35S]methionine, [3H]mannose, and [3H]glucosamine or externally with [3H]borohydride after galactose oxidase treatment. Four structural proteins, with MrS of about 58,000 (E1), 47,000 (E2a), 42,000 (E2b), and 33,000 (C), were resolved ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.46.3.964-973.1983
更新日期:1983-06-01 00:00:00
abstract::Human MxA protein accumulates in the cytoplasm of interferon-treated cells and inhibits the multiplication of several RNA viruses, including Thogoto virus (THOV), a tick-borne orthomyxovirus that transcribes and replicates its genome in the cell nucleus. The antiviral mechanism of MxA was investigated by using two alt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.1.560-563.2000
更新日期:2000-01-01 00:00:00
abstract::Prior studies have demonstrated that a small proportion of blood lymphocytes from patients with human cytomegalovirus (HCMV) infection express only the viral immediate-early (IE) genes (L. Einhorn and A. Ost, J. Infect. Dis. 149:207-214, 1984; G. P. A. Rice, R. D. Schrier, and M. B. A. Oldstone, Proc. Natl. Acad. Sci....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.7.3026-3033.1989
更新日期:1989-07-01 00:00:00
abstract::Antigens detected by the complement-fixation (CF) test were prepared from BHK-21 cells infected with Pichinde virus. The preparations contained two antigens demonstrable by immunodiffusion. The antigen present in abundance was heat stable, Pronase resistant, and had a molecular weight of 20,000 to 30,000 as estimated ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.22.1.175-186.1977
更新日期:1977-04-01 00:00:00
abstract::Replication of the genomic RNA of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by replicase polyproteins that are processed by two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro). Previously, we showed that SARS-CoV PLpro processes the replicase polyprotein at three ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.24.15189-15198.2005
更新日期:2005-12-01 00:00:00
abstract::The synthesis of viral RNA by wild-type vesicular stomatitis virus (L(1)VSV) and a small, plaque-size mutant (S(2)VSV) was studied in vitro and in chicken embryo (CE) and mouse L-cell cultures. Virus-specific RNA synthesized in CE or L cells infected with either L(1) or S(2)VSV at low multiplicity was of the same size...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.2.253-264.1973
更新日期:1973-08-01 00:00:00
abstract::A series of plasmids containing hepatitis A virus (HAV) cDNA was constructed such that positive-strand HAV RNA could be transcribed with T7 RNA polymerase. The plasmids differed in the number of 5'-terminal nucleotides representing the junctions between vectors and HAV sequences that were present in the transcripts. W...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.5.2757-2760.1991
更新日期:1991-05-01 00:00:00