Abstract:
:The human cytomegalovirus (HCMV) UL138 protein downregulates the cell surface expression of the multidrug resistance-associated protein 1 (MRP1) transporter. We examined the genetic requirements within UL138 for MRP1 downregulation. We determined that the acidic cluster dileucine motif is essential for UL138-mediated downregulation of MRP1 steady-state levels and inhibition of MRP1 efflux activity. We also discovered that the naturally occurring UL138 protein isoforms, the full-length long isoform of UL138 and a short isoform missing the N-terminal membrane-spanning domain, have different abilities to inhibit MRP1 function. Cells expressing the long isoform of UL138 show decreased MRP1 steady-state levels and fail to efflux an MRP1 substrate. Cells expressing the short isoform of UL138 also show decreased MRP1 levels, but the magnitude of the decrease is not the same, and they continue to efficiently efflux an MRP1 substrate. Thus, the membrane-spanning domain, while dispensable for a UL138-mediated decrease in MRP1 protein levels, is necessary for a functional inhibition of MRP1 activity. Our work defines the genetic requirements for UL138-mediated MRP1 downregulation and anticipates the possible evolution of viral escape mutants during the use of therapies targeting this function of UL138.IMPORTANCE HCMV UL138 curtails the activity of the MRP1 drug transporter by reducing its steady-state levels, leaving cells susceptible to killing by cytotoxic agents normally exported by MRP1. It has been suggested in the literature that capitalizing on this UL138-induced vulnerability could be a potential antiviral strategy against virally infected cells, particularly those harboring a latent infection during which UL138 is one of the few viral proteins expressed. Therefore, identifying the regions of UL138 required for MRP1 downregulation and predicting genetic variants that may be selected upon UL138-targeted chemotherapy are important ventures. Here we present the first structure-function examination of UL138 activity and determine that its transmembrane domain and acidic cluster dileucine Golgi sorting motif are required for functional MRP1 downregulation.
journal_name
J Viroljournal_title
Journal of virologyauthors
Gelbmann CB,Kalejta RFdoi
10.1128/JVI.00430-19subject
Has Abstractpub_date
2019-05-15 00:00:00issue
11eissn
0022-538Xissn
1098-5514pii
JVI.00430-19journal_volume
93pub_type
杂志文章abstract::Glycoprotein B (gB) of herpes simplex virus (HSV) is one of four glycoproteins essential for viral entry and cell fusion. Recently, paired immunoglobulin-like type 2 receptor (PILRalpha) was identified as a receptor for HSV type 1 (HSV-1) gB. Both PILRalpha and a gD receptor were shown to participate in HSV-1 entry in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00087-09
更新日期:2009-08-01 00:00:00
abstract::We previously reported that nucleolin, a representative nucleolar marker, interacts with nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) through two independent regions of NS5B, amino acids 208 to 214 and 500 to 506. We also showed that truncated nucleolin that harbors the NS5B-binding region inhibited the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.7.3332-3340.2006
更新日期:2006-04-01 00:00:00
abstract:UNLABELLED:Phenotypic diversity in prion diseases can be specified by prion strains in which biological traits are propagated through an epigenetic mechanism mediated by distinct PrP(Sc) conformations. We investigated the role of host-dependent factors on phenotypic diversity of chronic wasting disease (CWD) in differe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01586-15
更新日期:2015-10-01 00:00:00
abstract::Expression of the human ADA cDNA encoded by the Moloney murine leukemia virus spliced RNA form is enhanced by intron-contained sequences. The presence of sequences corresponding to the viral gag gene in a Moloney murine leukemia virus-based vector results in the generation of 10- to 40-fold higher titers of virus. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.5.1647-1650.1987
更新日期:1987-05-01 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
更新日期:2019-02-19 00:00:00
abstract::Theiler murine encephalomyelitis virus (TMEV) infection of a mouse's central nervous system is biphasic: first the virus infects motor neurons (acute phase), and this is followed by a chronic phase in which the virus infects glial cells (primarily microglia and macrophages [M]) of the spinal cord white matter, leading...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03395-12
更新日期:2013-04-01 00:00:00
abstract::The temperature-sensitive and attenuated phenotypes of the Sabin type 1 vaccine strain of poliovirus result from numerous point mutations which occurred in the virulent Mahoney virus parent. One of these mutations is located in a 3D polymerase (3Dpol) codon (U-6203-->C, Tyr-73-->His) and is involved in attenuation in ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5278-5286.1995
更新日期:1995-09-01 00:00:00
abstract::The complete genomic sequence of a new Muscovy duck-origin reovirus (N-MDRV), strain J18 from China, was determined. The virus has a tricistronic S1 genome segment that is distinct from the originally described MDRV, which possesses a bicistronic S4 genome segment. Pairwise comparisons and phylogenetic analyses sugges...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02230-12
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.18.3.1155-1159.1976
更新日期:1976-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01885-17
更新日期:2018-01-30 00:00:00
abstract::Grasshoppers, Melanoplus sanguinipes (F.), infected with the grasshopper inclusion body virus (GIBV) showed a general torpor, took longer to develop, and had abnormally high rates of mortality. Infection was found only in the fat body, and developing viruses and inclusion bodies were observed in the nuclei and cytopla...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.3.6.605-610.1969
更新日期:1969-06-01 00:00:00
abstract::Broadly neutralizing antibodies (bnAbs) can prevent lentiviral infection in nonhuman primates and may slow the spread of human immunodeficiency virus type 1 (HIV-1). Although protection by passive transfer of human bnAbs has been demonstrated in monkeys, durable expression is essential for its broader use in humans. G...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00908-15
更新日期:2015-08-01 00:00:00
abstract::Chronic HIV infection is characterized by chronic immune activation and dysfunctional T cells with elevated intracellular cyclic AMP (cAMP), which inhibits the T cell activation capability. cAMP may be induced by prostaglandin E(2) following lipopolysaccharide (LPS)-induced upregulation of cyclooxygenase type 2 (COX-2...
journal_title:Journal of virology
pub_type: 杂志文章,随机对照试验
doi:10.1128/JVI.00073-11
更新日期:2011-07-01 00:00:00
abstract::Treatment with sodium dodecyl sulfate (SDS) converted the vaccinia virus strain IHD-J into particles of two types: (i) ghosts which possessed a thin-membrane vesicle derived from basement part of the virus membrane with attached lateral bodies and a membranous structure derived from the core wall and (ii) aggregates o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.3.929-938.1984
更新日期:1984-06-01 00:00:00
abstract::The prevailing hypothesis is that the intracellular site of budding of coronaviruses is determined by the localization of its membrane protein M (previously called E1). We tested this by analyzing the site of budding of four different coronaviruses in relation to the intracellular localization of their M proteins. Mou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.10.6523-6534.1994
更新日期:1994-10-01 00:00:00
abstract::Retroviruses are believed to induce tumors by acting as insertional mutagens that activate expression of cellular protooncogenes. Indeed, almost 90% of mouse mammary tumor virus (MMTV)-induced mammary tumors in C3H/He mice show upregulation of Int protooncogenes. We have analyzed three different MMTV variants [MMTV(C3...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.19.8876-8883.2000
更新日期:2000-10-01 00:00:00
abstract::Hepatitis B virus (HBV) DNA clones were propagated from 57 carriers with antibody to hepatitis B e antigen (HBeAg) and sequenced within nucleotides (nt) 1685 to 1926 including the core promoter (nt 1742 to 1849) and the pre-C region (nt 1814 to 1900). Mutations in the core promoter or those in the pre-C region, or bot...
journal_title:Journal of virology
pub_type: 临床试验,杂志文章
doi:10.1128/JVI.68.12.8102-8110.1994
更新日期:1994-12-01 00:00:00
abstract::The single-stranded DNA containing the Moloney murine leukemia virus origin for plus-strand synthesis was cloned in M13mp2 and used as a template for avian myeloblastosis virus reverse transcriptase in the presence of Moloney RNA which had been treated with pancreatic RNase A. The RNA pieces containing the polypurine ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.3.686-691.1984
更新日期:1984-03-01 00:00:00
abstract::The DNAs of the five nondefective adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid viruses contain overlapping segments of the early region of wild-type SV40 DNA. The complementary DNA strands of these five viruses have been separated with synthetic polyribonucleotides in isopycnic cesium chloride gradients. The relat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.3.677-689.1974
更新日期:1974-03-01 00:00:00
abstract::Envelope glycoprotein (Env) reactivity (ER) describes the propensity of human immunodeficiency virus type 1 (HIV-1) Env to change conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that fav...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01558-13
更新日期:2014-01-01 00:00:00
abstract::Herpes simplex virus 1 (HSV-1) envelope glycoprotein D (gD) plays an essential role in viral entry. The functional regions of gD responsible for viral entry have been mapped to its extracellular domain, whereas the gD cytoplasmic domain plays no obvious role in viral entry. Thus far, the role(s) of the gD cytoplasmic ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01396-16
更新日期:2016-10-28 00:00:00
abstract::The hepatitis C virus (HCV) causes chronic hepatitis in most infected individuals by evading host immune defenses. In this investigation, we show that HCV-infected cells may go undetected in the immune system by suppressing major histocompatibility complex (MHC) class I antigen presentation to cytotoxic T lymphocytes....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.21.11644-11650.2003
更新日期:2003-11-01 00:00:00
abstract::We investigated the features of the Moloney murine sarcoma virus leader sequence necessary for RNA packaging function by using a deletion analysis approach. We found that sequences that extend beyond those characterized genetically in previous reports are important for optimal packaging efficiency. A fragment covering...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.9.4643-4648.2002
更新日期:2002-05-01 00:00:00
abstract::Our previous observations indicated that upon infection with minute virus of mice (MVM), Ehrlich ascites cells lose a transcription elongation activity which is essential for the readthrough of the MVM attenuator. This was monitored by the ability of extracts from uninfected but not from infected cells to support read...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.4.2741-2745.1994
更新日期:1994-04-01 00:00:00
abstract::African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs that has significant economic consequences for the swine industry. The control of African swine fever (ASF) has been hampered by the unavailability of vaccines. Successful experimental vaccines hav...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01760-16
更新日期:2016-12-16 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::The human immunodeficiency virus (HIV) and the closely related simian immunodeficiency virus (SIV) induce profound immune dysfunction in primate species. The present studies show that cell populations infected in vitro with SIV exhibit increases in major histocompatibility complex (MHC) class II antigen expression. Ce...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.5.1421-1426.1987
更新日期:1987-05-01 00:00:00
abstract::Leukocyte access into the central nervous system (CNS) parenchyma is tightly regulated by the blood-brain barrier (BBB). Leukocyte migration through the endothelial cell wall into the perivascular space is well characterized; however, mechanisms regulating their penetration through the glia limitans into the parenchym...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00051-10
更新日期:2010-05-01 00:00:00
abstract::Hepatitis delta virus (HDV) replicates by RNA-dependent RNA synthesis according to a double rolling circle model. Also synthesized during replication is a 0.8-kb, polyadenylated mRNA encoding the hepatitis delta antigen (HDAg). It has been proposed that this mRNA species represents the initial product of HDV RNA repli...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.7.5449-5456.1998
更新日期:1998-07-01 00:00:00
abstract:UNLABELLED:Since the 1960s, simian hemorrhagic fever virus (SHFV; Nidovirales, Arteriviridae) has caused highly fatal outbreaks of viral hemorrhagic fever in captive Asian macaque colonies. However, the source(s) of these outbreaks and the natural reservoir(s) of this virus remain obscure. Here we report the identifica...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02203-14
更新日期:2014-11-01 00:00:00