Abstract:
:Dengue virus (DENV) is a mosquito-borne flavivirus responsible for dengue disease, a major human health concern for which no specific therapies are available. Like other viruses, DENV relies heavily on the host cellular machinery for productive infection. In this study, we performed a genome-wide CRISPR-Cas9 screen using haploid HAP1 cells to identify host genes important for DENV infection. We identified DPM1 and -3, two subunits of the endoplasmic reticulum (ER) resident dolichol-phosphate mannose synthase (DPMS) complex, as host dependency factors for DENV and other related flaviviruses, such as Zika virus (ZIKV). The DPMS complex catalyzes the synthesis of dolichol-phosphate mannose (DPM), which serves as mannosyl donor in pathways leading to N-glycosylation, glycosylphosphatidylinositol (GPI) anchor biosynthesis, and C- or O-mannosylation of proteins in the ER lumen. Mutation in the DXD motif of DPM1, which is essential for its catalytic activity, abolished DPMS-mediated DENV infection. Similarly, genetic ablation of ALG3, a mannosyltransferase that transfers mannose to lipid-linked oligosaccharide (LLO), rendered cells poorly susceptible to DENV. We also established that in cells deficient for DPMS activity, viral RNA amplification is hampered and truncated oligosaccharides are transferred to the viral prM and E glycoproteins, affecting their proper folding. Overall, our study provides new insights into the host-dependent mechanisms of DENV infection and supports current therapeutic approaches using glycosylation inhibitors to treat DENV infection.IMPORTANCE Dengue disease, which is caused by dengue virus (DENV), has emerged as the most important mosquito-borne viral disease in humans and is a major global health concern. DENV encodes only few proteins and relies on the host cell machinery to accomplish its life cycle. The identification of the host factors important for DENV infection is needed to propose new targets for antiviral intervention. Using a genome-wide CRISPR-Cas9 screen, we identified DPM1 and -3, two subunits of the DPMS complex, as important host factors for the replication of DENV as well as other related viruses such as Zika virus. We established that DPMS complex plays dual roles during viral infection, both regulating viral RNA replication and promoting viral structural glycoprotein folding/stability. These results provide insights into the host molecules exploited by DENV and other flaviviruses to facilitate their life cycle.
journal_name
J Viroljournal_title
Journal of virologyauthors
Labeau A,Simon-Loriere E,Hafirassou ML,Bonnet-Madin L,Tessier S,Zamborlini A,Dupré T,Seta N,Schwartz O,Chaix ML,Delaugerre C,Amara A,Meertens Ldoi
10.1128/JVI.01751-19subject
Has Abstractpub_date
2020-03-17 00:00:00issue
7eissn
0022-538Xissn
1098-5514pii
JVI.01751-19journal_volume
94pub_type
杂志文章abstract::By marker rescue with cloned herpes simplex virus 2 DNA fragments, we have mapped the temperature-sensitive mutations of a series of herpes simplex virus 2 mutants to a region of the herpes simplex virus 2 genome that lies within or near the coding sequences for the major DNA-binding protein, ICP8. In cells infected w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.45.1.332-342.1983
更新日期:1983-01-01 00:00:00
abstract::Woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV) are closely similar with respect to genomic organization, host antiviral responses, and pathobiology of the infection. T-cell immunity against viral nucleocapsid (HBcAg or WHcAg) has been shown to play a critical role in viral clearance and protection against...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.19.9068-9076.2001
更新日期:2001-10-01 00:00:00
abstract::The unique region of the capsid protein VP1 (VP1u) of human parvovirus B19 (B19) elicits a dominant immune response and has a phospholipase A(2) (PLA(2)) activity, which is necessary for the infection. In contrast to the rest of the parvoviruses, the VP1u of B19 is thought to occupy an external position in the virion,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01435-06
更新日期:2006-12-01 00:00:00
abstract::After rabies virus glycoprotein was treated with CNBr, the peptide mixture was fractionated by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. CNBr-cleaved peptide fragments were resolved into seven peptide bands under reducing conditions and six peptide bands under nonreducing conditions. The i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.2.595-602.1982
更新日期:1982-11-01 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
pub_type: 杂志文章
doi:10.1128/JVI.02672-08
更新日期:2009-08-01 00:00:00
abstract::In addition to PTAP L domains, primate lentiviruses carry Alix-binding motifs that include the recently described type 3 SREKPYKEVTEDLLHLNSLF sequence. We examined the requirements for the type 3 sequence motif in simian immunodeficiency virus SIV(smE543) and identified the (499)LNSLF(503) sequence as a key functional...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05284-11
更新日期:2011-11-01 00:00:00
abstract::The N terminus of the capsid protein (CA) undergoes a considerable conformational change when the human immunodeficiency virus (HIV) protease cleaves it free from the Pr55(Gag) polyprotein. This rearrangement is thought to facilitate the establishment of specific CA-CA interactions that are required for the formation ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.14.8009-8018.2003
更新日期:2003-07-01 00:00:00
abstract::BALB/c mice sensitized to herpes simplex virus type 1 (HSV-1) develop a vigorous delayed-type hypersensitivity (DTH) response upon intradermal virus antigen challenge. Although CD4(+) T cells are a key mediator of this response, neutrophils are the most abundant cells at the antigen challenge site both initially and a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.16.8050-8057.2002
更新日期:2002-08-01 00:00:00
abstract::To study the variability of human immunodeficiency virus type 1 (HIV-1), we used immunotoxins to select for variants within a population of H9 cells persistently infected with a molecular clone of HIV-1 designated NL4-3. Chimeric immunotoxin CD4-PE40 (a chimeric fusion protein consisting of the amino-terminal two doma...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.1.75-81.1995
更新日期:1995-01-01 00:00:00
abstract::Functional defects in cytotoxic CD8(+) T cell responses arise in chronic human viral infections, but the mechanisms involved are not well understood. In mice, CD4 cell-mediated interleukin-21 (IL-21) production is necessary for the maintenance of CD8(+) T cell function and control of persistent viral infections. To in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02030-10
更新日期:2011-01-01 00:00:00
abstract::Human cytomegalovirus (HCMV) is a prototypic member of the betaherpesvirus family. The HCMV virion is composed of a large DNA genome encapsidated within a nucleocapsid, which is wrapped within an inner proteinaceous tegument and an outer lipid envelope containing viral glycoproteins. Although genome encapsidation clea...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.10.5147-5155.2002
更新日期:2002-05-01 00:00:00
abstract::The specificity of herpes simplex virus type 1-specific cytotoxic T cells was examined with target cells expressing either input viral structural antigens or antigens resulting from permissive infection or cells from an interrupted infection in which they expressed predominantly nonstructural immediate-early proteins....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.7.2265-2273.1988
更新日期:1988-07-01 00:00:00
abstract::A virus (M-7) isolated from baboon placental tissue demonstrates many similarities to endogenous feline virus RD-114. Immunodiffusion analysis shows a group-specific antigen (gs-1) line of identity between M-7 and RD-114. Anti-RD-114 DNA polymerase IgG inhibits M-7 polymerase by 57% compared to 97% for RD-114. M-7 vir...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.1.133-138.1974
更新日期:1974-07-01 00:00:00
abstract::The binding properties of seven CD4-blocking monoclonal antibodies raised against recombinant gp120 of human immunodeficiency virus type 1 strain MN (HIV-1MN) and two CD4-blocking monoclonal antibodies to recombinant envelope glycoproteins gp120 and gp160 of substrain IIIB of HIVLAI were analyzed. With a panel of reco...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.6179-6191.1993
更新日期:1993-10-01 00:00:00
abstract::Utilization of internal ribosome entry segment (IRES) structures in the 5' noncoding region (5'NCR) of picornavirus RNAs for initiation of translation requires a number of host cell factors whose distribution may vary in different cells and whose requirement may vary for different picornaviruses. We have examined the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.12.9668-9675.1998
更新日期:1998-12-01 00:00:00
abstract::Analysis of six monoclonal antibody-resistant (mar) mutants in herpes simplex virus type 1 glycoprotein B identified two type-common (II and III) and two type-specific (I and IV) antigenic sites on this molecule. To derive additional information on the location of these sites, mar mutations were mapped and nucleotide ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.2.730-738.1989
更新日期:1989-02-01 00:00:00
abstract::The first 86 residues of the Rous sarcoma virus (RSV) Gag protein form a membrane-binding (M) domain that directs Gag to the plasma membrane during budding. Unlike other retroviral Gag proteins, RSV Gag is not myristylated; however, the RSV M domain does contain 11 basic residues that could potentially interact with a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.23.11222-11229.2000
更新日期:2000-12-01 00:00:00
abstract:UNLABELLED:Numerous animal and plant viruses are transmitted by arthropod vectors in a persistent, circulative manner. Tomato yellow leaf curl virus (TYLCV) is transmitted by the sweet potato whitefly Bemisia tabaci. We report here that infection with Rickettsia spp., a facultative endosymbiont of whiteflies, altered T...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00071-14
更新日期:2014-05-01 00:00:00
abstract::The major structural glycoprotein E2 of classical swine fever virus (CSFV) is responsible for eliciting neutralizing antibodies and conferring protective immunity. The current structural model of this protein predicts its surface-exposed region at the N terminus with a short stretch of the C-terminal residues spanning...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.24.11619-11625.2000
更新日期:2000-12-01 00:00:00
abstract::The ascomycete Botrytis porri causes clove rot and leaf blight of garlic worldwide. We report here the biological and molecular features of a novel bipartite double-stranded RNA (dsRNA) mycovirus named Botrytis porri RNA virus 1 (BpRV1) from the hypovirulent strain GarlicBc-72 of B. porri. The BpRV1 genome comprises t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00292-12
更新日期:2012-06-01 00:00:00
abstract::Mucosal surfaces are the primary portals for human immunodeficiency virus (HIV) transmission. Because systemic immunization, in general, does not induce effective mucosal immune responses, a mucosal HIV vaccine is urgently needed. For this study, we developed papillomavirus pseudoviruses that express HIV-1 Gag. The ps...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.19.10249-10257.2004
更新日期:2004-10-01 00:00:00
abstract::Genomic replication of the negative-strand RNA viruses is dependent upon protein synthesis. To examine the requirement for protein synthesis in replication, we developed an in vitro system that supports the genome replication of defective interfering particles of the negative-strand rhabdovirus vesicular stomatitis vi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.2.303-309.1984
更新日期:1984-02-01 00:00:00
abstract::Extracts from poliovirus-infected HeLa cells are unable to translate vesicular stomatitis virus or cellular mRNAs in vitro, probably reflecting the poliovirus-induced inhibition of host cell protein synthesis which occurs in vivo. Crude initiation factors from uninfected HeLa cells are able to restore translation of v...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.42.1.200-207.1982
更新日期:1982-04-01 00:00:00
abstract::Venezuelan equine encephalitis (VEE) virus antigenic subtypes and varieties are considered either epidemic/epizootic or enzootic. In addition to epidemiological differences between the epidemic and enzootic viruses, several in vitro and in vivo laboratory markers distinguishing the viruses have been identified, includ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.9.4258-4263.2000
更新日期:2000-05-01 00:00:00
abstract::Transmission of arenaviruses from rodent hosts to humans is generally thought to occur through inhalation or ingestion of dust or droplets containing viral particles. Here we demonstrate that two identified arenavirus receptors, alpha-dystroglycan (alpha-DG) and transferrin receptor 1 (TfR1), are expressed in polarize...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00100-08
更新日期:2008-06-01 00:00:00
abstract::Hepatitis C virus (HCV) nonstructural protein 4B (NS4B) is an integral membrane protein, which plays an important role in the organization and function of the HCV replication complex (RC). Although much is understood about its amphipathic N-terminal and C-terminal domains, we know very little about the role of the tra...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02298-10
更新日期:2011-07-01 00:00:00
abstract::To combat emerging coronaviruses, developing safe and efficient platforms to evaluate viral protease activities and the efficacy of protease inhibitors is a high priority. Here, we exploit a biosafety level 2 (BSL-2) chimeric Sindbis virus system to evaluate protease activities and the efficacy of inhibitors directed ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01749-14
更新日期:2014-10-01 00:00:00
abstract::The reticuloendotheliosis viruses (REVs), originally isolated from avian species, constitute a group of retroviruses which are more closely related to mammalian retroviruses than to other avian retroviruses. The envelope glycoproteins of members of the REV group display a striking amino acid sequence identity with a g...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.6.3448-3454.1992
更新日期:1992-06-01 00:00:00
abstract::By means of both electron microscopy and plaque assay techniques, 10(-3)m Zn(2+) has been shown to reduce the adsorption rate of male-specific filamentous deoxyribonucleic acid bacteriophages to the tips of F pili. In contrast, 10(-3)m Zn(2+) did not affect the adsorption of male-specific ribonucleic acid phages to th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.10.4.869-871.1972
更新日期:1972-10-01 00:00:00
abstract::Recombinant vaccinia viruses containing the 22-kilodalton protein (matrixlike or 22K protein) or phosphoprotein gene from respiratory syncytial virus were constructed. These recombinant viruses expressed proteins which were immunoprecipitated by appropriate respiratory syncytial virus antibodies and comigrated with au...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.4.1683-1689.1990
更新日期:1990-04-01 00:00:00