Abstract:
:Lymphocyte antigen 6E (LY6E) is a GPI-anchored, interferon-inducible protein that has been shown to modulate viral infection in a cell type-dependent manner. Our recent work showed that LY6E promotes HIV-1 infection in some high-CD4-expressing cells, including human peripheral blood mononuclear cells (PBMCs) and the SupT1 cell line. In this work, we provide evidence that LY6E inhibits HIV-1 entry and spread in low-CD4-expressing Jurkat cells and human monocyte-derived macrophages (MDMs) through downregulation of the viral receptor CD4. We found that knockdown of LY6E in Jurkat cells and MDMs increases HIV-1 infection, yet overexpression of LY6E in Jurkat cells inhibits HIV-1 entry and replication. LY6E was found to be colocalized with CD4 on the plasma membrane of Jurkat cells and MDMs and enhances CD4 internalization. We artificially manipulated the CD4 level in Jurkat and SupT1 cells and found that overexpression of CD4 in Jurkat cells overcomes the inhibitory effect of LY6E; conversely, blocking the function of CD4 in SupT1 with a neutralizing antibody eliminates the enhancement of LY6E on HIV-1 entry. The CD4-dependent inhibitory phenotype of LY6E in low-CD4-expressing human MDMs can be recapitulated for a panel of transmitted founder viruses and laboratory-adapted HIV-1 strains. Given that HIV-1 can target low-CD4-expressing cells during acute infection yet replicates efficiently in high-CD4-expressing T cells at the late stage of disease, our observation that LY6E differentially modulates HIV-1 replication in a CD4-dependent manner has implications for understanding the complex roles of interferon (IFN)-induced proteins in AIDS pathogenesis.IMPORTANCE The role of IFN-induced genes (ISGs) in viral infection remains incompletely understood. While most ISGs are antiviral, some ISGs have been shown to promote viral infection, including HIV-1 infection. We previously showed that IFN-inducible LY6E protein promotes HIV-1 infection in human PMBCs and high-CD4-expressing SupT1 cells. Here we found that LY6E inhibits HIV-1 entry and replication in low-CD4-expressing MDMs and Jurkat cells. Mechanistically, we demonstrated that LY6E downregulates the cell surface receptor CD4, thus impairing the virus binding to target cells. This is in contrast to the situation of high-CD4-expressing cells, where LY6E predominantly promotes viral membrane fusion. The opposing role of IFN-inducible LY6E in modulating HIV-1 infection highlights the complex roles of ISGs in viral infection and viral pathogenesis.
journal_name
J Viroljournal_title
Journal of virologyauthors
Yu J,Liang C,Liu SLdoi
10.1128/JVI.01866-18subject
Has Abstractpub_date
2019-03-21 00:00:00issue
7eissn
0022-538Xissn
1098-5514pii
JVI.01866-18journal_volume
93pub_type
杂志文章abstract::Penetration of the nervous systems of suckling mice by prototype strains of the three mammalian reovirus serotypes was studied after footpad inoculation of a dose (10(7) PFU) representing 3.5 x 10(3) 50% lethal doses (LD50) for reovirus type 3 Dearing and less than 1 LD50 for reoviruses type 1 Lang and type 2 Jones. T...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.1.123-131.1991
更新日期:1991-01-01 00:00:00
abstract::Spleen necrosis virus productively infects avian and rat cells. The average number of molecules of unintegrated and integrated viral DNA in cells at different times after infection was determined by hybridization and transfection assays. Shortly after infection, there was a transient accumulation of an average of abou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.31.2.376-388.1979
更新日期:1979-08-01 00:00:00
abstract::Strains of Sindbis virus differ in their virulence for mice of different ages; this variation is related in large part to variations in the amino acid compositions of E1 and E2, the surface glycoproteins. The comparative pathogenesis of Sindbis virus strains which are virulent or avirulent for newborn mice has not bee...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2041-2046.1990
更新日期:1990-05-01 00:00:00
abstract::Using synthetic peptides, we characterized the B-lymphocyte (antibody) and T-lymphocyte (proliferation) responses to an immunodominant epitope of human immunodeficiency virus type 1 (HIV-1) located near the amino-terminal end of the transmembrane glycoprotein (env amino acids 598 to 609). Both immunoglobulin M (IgM) a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.8.2531-2536.1988
更新日期:1988-08-01 00:00:00
abstract::Rotavirus nonstructural protein 4 (NSP4) induces dramatic changes in cellular calcium homeostasis. These include increased endoplasmic reticulum (ER) permeability, resulting in decreased ER calcium stores and activation of plasma membrane (PM) calcium influx channels, ultimately causing a 2- to 4-fold elevation in cyt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02629-13
更新日期:2013-12-01 00:00:00
abstract::Human T-cell lymphotropic virus type 1 (HTLV-1) is transmitted through a viral synapse and enters target cells via interaction with the glucose transporter GLUT1. Here, we show that Neuropilin-1 (NRP1), the receptor for semaphorin-3A and VEGF-A165 and a member of the immune synapse, is also a physical and functional p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02719-05
更新日期:2006-07-01 00:00:00
abstract::Reassortant viruses which possessed the hemagglutinin and neuraminidase genes of wild-type human influenza A viruses and the remaining six RNA segments (internal genes) of the avian A/Pintail/Alberta/119/79 (H4N6) virus were previously found to be attenuated in humans. To study the genetic basis of this attenuation, w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.9.2857-2863.1987
更新日期:1987-09-01 00:00:00
abstract::Induction of apoptotic cell death generally requires the participation of cysteine proteases belonging to the caspase family. However, and similar to most cell types, mouse fibroblasts are normally resistant to tumor necrosis factor alpha (TNF-alpha)-induced apoptosis. Surprisingly, TNF-alpha treatment of vaccinia vir...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.16.7470-7477.2000
更新日期:2000-08-01 00:00:00
abstract::Human adenovirus type 12 was propagated on human embryonic kidney cells, and the specific infectivities of intra- and extracellular virus particles were compared between 48 and 104 h after infection. Released virions exhibited a specific infectivity of up to 10 times higher than that of intracellular particles. The in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.55.1.117-125.1985
更新日期:1985-07-01 00:00:00
abstract::The yield of G418-resistant Huh7 cell clones bearing subgenomic dicistronic GB virus B (GBV-B) is significantly affected by the insertion of a portion of the viral core gene between the GBV-B 5' untranslated region and the exogenous neomycin phosphotransferase selector gene (A. De Tomassi, M. Pizzuti, R. Graziani, A. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.13.7502-7509.2003
更新日期:2003-07-01 00:00:00
abstract::Polyacrylamide gel electrophoresis and tryptic peptide fingerprint analysis of the proteins made in a cell-free system derived from L-cells and immunoprecipitated with simian virus 40 (SV40) anti-T serum demonstrated that both SV40 large-T and small-T antigens are synthesized in vitro in response to mRNA isolated from...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.28.1.154-170.1978
更新日期:1978-10-01 00:00:00
abstract::Similar to other positive-sense, single-stranded RNA viruses, hepatitis C virus (HCV) replicates its genome in a remodeled intracellular membranous structure known as the membranous web (MW). To date, the process of MW formation remains unclear. It is generally acknowledged that HCV nonstructural protein 4B (NS4B) can...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01785-12
更新日期:2012-12-01 00:00:00
abstract::Although combination therapy allows the suppression of human immunodeficiency virus type 1 (HIV-1) viremia to undetectable levels, eradication has not been achieved because the virus persists in cellular reservoirs, particularly the latent reservoir in resting CD4(+) T lymphocytes. We previously established a simian i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01396-06
更新日期:2007-02-01 00:00:00
abstract::Spanins are bacteriophage lysis proteins responsible for disruption of the outer membrane, the final step of Gram-negative host lysis. The absence of spanins results in a terminal phenotype of fragile spherical cells. The phage T1 employs a unimolecular spanin gp11 that has an N-terminal lipoylation signal and a C-ter...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00380-18
更新日期:2018-10-29 00:00:00
abstract::Herpesviruses are members of a diverse family of viruses that colonize all vertebrates from fish to mammals. Although more than one hundred herpesviruses exist, all are nearly identical architecturally, with a genome consisting of a linear double-stranded DNA molecule (100 to 225 kbp) protected by an icosahedral capsi...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.01169-10
更新日期:2010-12-01 00:00:00
abstract::The intranuclear structure of parental adenovirus 2 DNA was studied using digestion with micrococcal nuclease as a probe. When cultures were infected with 32P-labeled virions, at a multiplicity of 3,000 particles per cell, 14 to 21% of parental DNA penetrated the cell and reached the nucleus. Of this parental DNA, 60%...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.3.888-898.1979
更新日期:1979-03-01 00:00:00
abstract::Primary telencephalic cultures derived from neonatal Wistar Furth rats were able to support the growth of coronavirus JHM if a viable neuronal population was maintained. This occurred under serum-free defined, but not serum-supplemented, growth conditions. The importance of neurons in establishing infections in mixed ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.9.5013-5028.1991
更新日期:1991-09-01 00:00:00
abstract::The Vpr accessory gene product of human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus is believed to play a role in permitting entry of the viral core into the nucleus of nondividing cells. A second role for Vpr was recently suggested by Rogel et al. (M. E. Rogel, L. I. Wu, and M. Emerman, J. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.6705-6711.1995
更新日期:1995-11-01 00:00:00
abstract::During the S phase of the eukaryotic cell cycle and in virus-infected cells, DNA replication takes place at discrete sites in the nucleus, although it is not clear how the proteins involved in the replicative process are directed to these sites. Nuclear factor I is a cellular, sequence-specific DNA-binding protein uti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.5.3140-3150.1992
更新日期:1992-05-01 00:00:00
abstract::Marburg virus, a filovirus, causes severe hemorrhagic fever with hitherto poorly understood molecular pathogenesis. We have investigated here the vectorial transport of the surface protein GP of Marburg virus in polarized epithelial cells. To this end, we established an MDCKII cell line that was able to express GP per...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.3.1274-1283.2001
更新日期:2001-02-01 00:00:00
abstract::Acute arenavirus disease in primates, like Lassa hemorrhagic fever in humans, begins with flu-like symptoms and leads to death approximately 2 weeks after infection. Our goal was to identify molecular changes in blood that are related to disease progression. Rhesus macaques (Macaca mulatta) infected intravenously with...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00536-07
更新日期:2007-08-01 00:00:00
abstract::Jurkat T-cell clones, stably expressing the human immunodeficiency virus type 1 (HIV-1) Vpr protein, exhibited an impaired susceptibility to HIV-1 infection. A marked down-modulation of surface CD4 receptors was detected in Vpr-expressing clones with respect to control cells. Likewise, a reduced CD4 expression was als...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.21.10207-10211.2000
更新日期:2000-11-01 00:00:00
abstract::A novel phage lambda mutation, called dc10, which interferes with proper lambda head assembly has been isolated and characterized. Phage lambda carrying this mutation is (i) unable to form plaques at 30 or 37 degrees C but does so at 42 degrees C and (ii) unable to form plaques at 42 degrees C on pN-constitutive hosts...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.2.782-788.1979
更新日期:1979-02-01 00:00:00
abstract::Resistance or susceptibility of various mouse strains to central nervous system disease caused by different strains of coronavirus is well known. Data from the present study draw attention to an additional, genetically determined mechanism controlling CV infections. The resistance to A59 and JHM virus (JHMV) associate...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3371-3377.1988
更新日期:1988-09-01 00:00:00
abstract::Infection of cells with herpes simplex virus type 1 (HSV-1) results in a rapid alteration of phosphorylation on the large subunit of cellular RNA polymerase II (RNAP II), most likely on its C-terminal domain (S. A. Rice, M. C. Long, V. Lam, C. A. Spencer, J. Virol. 68:988-1001, 1994). This phosphorylation modification...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5550-5559.1995
更新日期:1995-09-01 00:00:00
abstract::The matrix (M1) protein of influenza virus is a major structural component, involved in regulation of viral ribonucleoprotein transport into and out of the nucleus. Early in infection, M1 is distributed in the nucleus, whereas later, it is localized predominantly in the cytoplasm. Using immunofluorescence microscopy a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.1.439-445.1995
更新日期:1995-01-01 00:00:00
abstract::The human immunodeficiency virus Tat protein is essential for virus replication and is a candidate vaccine antigen. Macaques immunized with Tat or chemically modified Tat toxoid having the same clade B sequence developed strong antibody responses. We compared these antisera for their abilities to recognize diverse Tat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.5.3157-3166.2003
更新日期:2003-03-01 00:00:00
abstract::The African swine fever virus protein A238L inhibits activation of NFAT transcription factor by binding calcineurin and inhibiting its phosphatase activity. NFAT controls the expression of many immunomodulatory proteins. Here we describe a 14-amino-acid region of A238L that is needed and sufficient for binding to calc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.20.9412-9420.2000
更新日期:2000-10-01 00:00:00
abstract::Nucleotide sequencing and phylogenetic analysis of 10 recognized prototype strains of the porcine enterovirus (PEV) cytopathic effect (CPE) group I reveals a close relationship of the viral genomes to the previously sequenced strain F65, supporting the concept of a reclassification of this virus group into a new picor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.4.1620-1631.2001
更新日期:2001-02-01 00:00:00
abstract::Human papillomaviruses (HPVs) infect keratinocytes and induce proliferative lesions. In infected cells, viral gene products alter the activities of cellular proteins, such as Rb and p53, resulting in altered cell cycle response. It is likely that HPV gene products also alter expression of cellular genes. In this study...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.9.4174-4182.2000
更新日期:2000-05-01 00:00:00