Abstract:
:Endogenous retroviruses (ERV) are found throughout vertebrate genomes, and failure to silence their activation can have deleterious consequences on the host. Mutation and subsequent disruption of ERV loci is therefore an indispensable component of the cell-intrinsic defenses that maintain the integrity of the host genome. Abundant in vitro and in silico evidence have revealed that APOBEC3 cytidine-deaminases, including human APOBEC3G (hA3G), can potently restrict retrotransposition; yet, in vivo data demonstrating such activity is lacking, since no replication-competent human ERV have been identified. In mice deficient for Toll-like receptor 7 (TLR7), transcribed ERV loci can recombine and generate infectious ERV. In this study, we show that ectopic expression of hA3G can prevent the emergence of replication-competent, infectious ERV in Tlr7-/- mice. Mice encode one copy of Apobec3 in their genome. ERV reactivation in Tlr7-/- mice was comparable in the presence or absence of Apobec3 In contrast, expression of a human APOBEC3G transgene abrogated emergence of infectious ERV in the Tlr7-/- background. No ERV RNA was detected in the plasma of hA3G+Apobec3-/-Tlr7-/- mice, and infectious ERV virions could not be amplified through coculture with permissive cells. These data reveal that hA3G can potently restrict active ERV in vivo and suggest that expansion of the APOBEC3 locus in primates may have helped to provide for the continued restraint of ERV in the human genome.IMPORTANCE Although APOBEC3 proteins are known to be important antiviral restriction factors in both mice and humans, their roles in the restriction of endogenous retroviruses (ERV) have been limited to in vitro studies. Here, we report that human APOBEC3G expressed as a transgene in mice prevents the emergence of infectious ERV from endogenous loci. This study reveals that APOBEC3G can powerfully restrict active retrotransposons in vivo and demonstrates how transgenic mice can be used to investigate host mechanisms that inhibit retrotransposons and reinforce genomic integrity.
journal_name
J Viroljournal_title
Journal of virologyauthors
Treger RS,Tokuyama M,Dong H,Salas-Briceno K,Ross SR,Kong Y,Iwasaki Adoi
10.1128/JVI.00728-19subject
Has Abstractpub_date
2019-09-30 00:00:00issue
20eissn
0022-538Xissn
1098-5514pii
JVI.00728-19journal_volume
93pub_type
杂志文章abstract::Human T-cell leukemia virus (HTLV) Tax protein has been implicated in the HTLV oncogenic process, primarily due to its pleiotropic effects on cellular genes involved in growth regulation and cell cycle control. To date, several approaches attempting to correlate Tax activation of the CREB/activating transcription fact...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.6.2655-2662.2000
更新日期:2000-03-01 00:00:00
abstract::We have previously described several helper independent vector constructions (S. Hughes and E. Kosik, Virology 136:89-99, 1984; J. Sorge and S. H. Hughes, J. Mol. Appl. Genet. 1:547-599, 1982; J. Sorge, B. Ricci, and S. Hughes, J. Virol. 48:667-675, 1983), all of which derive from Rous sarcoma virus. In this report we...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.10.3004-3012.1987
更新日期:1987-10-01 00:00:00
abstract::Treatment of Friend erythroleukemia cells (FLC) with gamma interferon (IFN-gamma) in the presence of anti-IFN-beta antibodies reduces the effectiveness of the antiviral state and the induction of 2'-5'-oligoadenylate synthetase activity, indicating that the antiviral activity of IFN-gamma in FLC is in part mediated by...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.8.4130-4136.1991
更新日期:1991-08-01 00:00:00
abstract::We have previously described a nonconditional mutant of avian sarcoma virus (SE21Q1b) which fails to package viral RNA (Gallis et al., Virology 94:146-161, 1979; Linial et al., Cell 15:1371-1381, 1978). Quail cells transformed by SE21Q1b contain normal amounts of intracellular viral mRNA's for src, env, and gag-pol an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.2.450-456.1980
更新日期:1980-11-01 00:00:00
abstract::Human cytomegalovirus (HCMV) has emerged as a clinically opportunistic pathogen that targets multiple types of ocular cells and tissues, including the iris region of the uveal tract during anterior uveitis. In this report, we used primary cultures of human iris stroma (HIS) cells derived from human eye donors to inves...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00109-15
更新日期:2015-05-01 00:00:00
abstract::The isolation and characterization of an adenovirus mutant, Ad5dl802r1, containing two independent deletions in the 72-kilodalton (kDa) DNA-binding protein (DBP) gene is described. The two deletions remove amino acids 23 through 105 of DBP, resulting in the production of a 50-kDa product. Expression of this truncated ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.2289-2299.1989
更新日期:1989-05-01 00:00:00
abstract::Human cytomegalovirus (HCMV) glycoprotein B (gB), encoded by the UL55 open reading frame, is an essential envelope glycoprotein involved in cell attachment and entry. Previously, we identified residue serine 900 (Ser900) as a unique site of reversible casein kinase 2 phosphorylation in the cytoplasmic domain of HCMV g...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.1.285-293.2004
更新日期:2004-01-01 00:00:00
abstract::We have investigated the effect of Xenopus laevis p53 (Xp53) on transcription from a variety of promoters which are regulated by mouse p53 using a chloramphenicol acetyltransferase reporter system. Although Xp53 transactivated promoters that are up-regulated by mouse p53, it was unable to cause repression. This abilit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.11.7178-7187.1994
更新日期:1994-11-01 00:00:00
abstract::Two essential gene products of herpes simplex virus type 1, the viral DNA polymerase (pol) and UL42, its accessory protein, physically and functionally interact to form the core of the viral DNA replication complex. Understanding this essential interaction would provide a basis from which to develop novel anti-herpesv...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.5922-5931.1993
更新日期:1993-10-01 00:00:00
abstract:UNLABELLED:Despite encoding multiple viral proteins that modulate the retinoblastoma (Rb) protein in a manner classically defined as inactivation, human cytomegalovirus (HCMV) requires the presence of the Rb protein to replicate efficiently. In uninfected cells, Rb controls numerous pathways that the virus also command...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01718-15
更新日期:2015-12-01 00:00:00
abstract::The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00045-17
更新日期:2017-04-28 00:00:00
abstract::Cells nonproductively transformed by a variant of the Snyder-Theilen strain of feline sarcoma virus (FeSV) expressed an 85,000-dalton polyprotein (P85) with associated tyrosine-specific protein kinase activity. We identified within this polyprotein a single tyrosine acceptor site for its enzyme activity. This acceptor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.3.886-894.1981
更新日期:1981-06-01 00:00:00
abstract::Viral myocarditis is an important human disease, and reovirus-induced murine myocarditis provides an excellent model system for study. Cardiac myocytes, like neurons in the central nervous system, are not replenished, yet there is no cardiac protective equivalent to the blood-brain barrier. Thus, cardiac myocytes may ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01172-07
更新日期:2007-12-01 00:00:00
abstract::We have previously identified 11 epitopes located in two topologically nonoverlapping antigenic sites (A and B) and a third bridging site (C) on the human type 3 parainfluenza virus (PIV3) hemagglutinin-neuraminidase (HN) glycoprotein by using monoclonal antibodies (MAbs) which inhibit hemagglutination and virus infec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.1.90-96.1986
更新日期:1986-10-01 00:00:00
abstract::Neurotropic coronavirus induces acute encephalomyelitis and demyelination in mice. Infection of BALB/c (H-2(d)) mice expressing a dominant negative gamma interferon (IFN-gamma) receptor specifically in oligodendrocytes was examined to determine the influence of IFN-gamma signaling on pathogenesis. Inhibition of IFN-ga...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02373-09
更新日期:2010-03-01 00:00:00
abstract::Bacterial lipopolysaccharide (LPS) induces interferon (IFN) secretion and an antiviral state in murine peritoneal macrophages (PM). These cells secrete predominantly IFN-beta, as shown by neutralization assays with monoclonal antibodies. Secretion of IFN-beta is also induced in PM by IFN-gamma. LPS and IFN-gamma syner...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.6.2785-2789.1989
更新日期:1989-06-01 00:00:00
abstract::Herpesviruses utilize different origins of replication during lytic versus latent infection. Latent DNA replication depends on host cellular DNA replication machinery, whereas lytic cycle DNA replication requires virally encoded replication proteins. In lytic DNA replication, the lytic origin (ori-Lyt) is bound by a v...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.10.5578-5588.2003
更新日期:2003-05-01 00:00:00
abstract:UNLABELLED:Neutralizing antibodies that target the hemagglutinin of influenza virus either inhibit binding of hemagglutinin to cellular receptors or prevent the low-pH-induced conformational change in hemagglutinin required for membrane fusion. In general, the former type of antibody binds to the globular head formed b...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00420-14
更新日期:2014-07-01 00:00:00
abstract::Cell lines were generated by cotransfection of Vero cells with pSV2neo and a plasmid containing the herpes simplex virus type 1 (HSV-1) EcoRI D fragment (coordinates 0.086 to 0.194). One such cell line (S22) contained the genes for alkaline exonuclease and several uncharacterized functions. Three mutant isolates of HS...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.1.91-99.1988
更新日期:1988-01-01 00:00:00
abstract::Three molecules have been identified as the main cellular factors required for binding and entry of human T-cell leukemia virus type 1 (HTLV-1): glucose transporter 1 (GLUT1), heparan sulfate (HS), and neuropilin 1 (NRP-1). However, the precise mechanism of HTLV-1 cell tropism has yet to be elucidated. Here, we examin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05783-11
更新日期:2012-03-01 00:00:00
abstract::Type 1 human immunodeficiency viruses encoding mutated nef reading frames are 10- to 30-fold less infectious than are isogenic viruses in which the nef gene is intact. This defect in infectivity causes nef-negative viruses to grow at an attenuated rate in vitro. To investigate the mechanism of Nef-mediated enhancement...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.7.4283-4290.1996
更新日期:1996-07-01 00:00:00
abstract::The DNA region encoding the complete herpes simplex virus type 1 (HSV-1) glycoprotein K (gK) was inserted into a baculovirus transfer vector, and recombinant viruses expressing gK were isolated. Four gK-related recombinant baculovirus-expressed peptides of 29, 35, 38, and 40 kDa were detected with polyclonal antibody ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.4.2347-2354.1994
更新日期:1994-04-01 00:00:00
abstract::Interferon regulatory factor 7 (IRF-7) is implicated in the regulation of Epstein-Barr virus (EBV) latency. EBV transforms primary B cells, and the major EBV oncoprotein, latent membrane protein 1 (LMP-1), is required for the process. LMP-1 both induces the expression of IRF-7 and activates the IRF-7 protein by phosph...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.23.12987-12995.2004
更新日期:2004-12-01 00:00:00
abstract::Adenovirus genomes consist of linear DNA molecules containing inverted terminal repeat sequences (ITRs) of 100 to 200 base pairs. The importance of identical termini for viability of adenoviruses was investigated. The viral strains used in this study were wild-type adenovirus type 5 (Ad5) and a variant Ad2 strain with...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.12.5133-5141.1989
更新日期:1989-12-01 00:00:00
abstract::Human cytomegalovirus (HCMV) glycoprotein US2 increases the proteasome-mediated degradation of major histocompatibility complex (MHC) class I heavy chain (HC), class II DR-alpha and DM-alpha proteins, and HFE, a nonclassical MHC protein. US2-initiated degradation of MHC proteins apparently involves the recruitment of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.8.4731-4738.2003
更新日期:2003-04-01 00:00:00
abstract::An immunodominant envelope glycoprotein is encoded by the human herpesvirus 8 (HHV-8) (also termed Kaposi's sarcoma-associated herpesvirus) K8.1 gene. The functional role of glycoprotein K8.1 is unknown, and recognizable sequence homology to K8.1 is not detectable in the genomes of most other closely related gammaherp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.23.11583-11593.2001
更新日期:2001-12-01 00:00:00
abstract::The transforming proteins of the small DNA tumor viruses, simian virus 40 (SV40), adenovirus, and human papillomavirus (HPV) target a number of identical cellular regulators whose functional abrogation is required for transformation. However, while both adenovirus E1A and SV40 large T transforming properties also depe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.8.6209-6219.1999
更新日期:1999-08-01 00:00:00
abstract:UNLABELLED:The live attenuated measles virus vaccine is highly immunostimulatory. Identification and characterization of its components that activate the innate immune response might provide new strategies and agents for the rational design and development of chemically defined adjuvants. In this study, we report on th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02161-15
更新日期:2015-11-25 00:00:00
abstract::HVEM (for herpesvirus entry mediator) is a member of the tumor necrosis factor receptor superfamily and mediates entry of many strains of herpes simplex virus (HSV) into normally nonpermissive Chinese hamster ovary (CHO) cells. We used sucrose density centrifugation to demonstrate that purified HSV-1 KOS virions bind ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.5.3595-3601.1998
更新日期:1998-05-01 00:00:00
abstract::Recently, significant numbers of individuals with primary human immunodeficiency virus (HIV) infection have been found to harbor viral strains with reduced susceptibility to antiretroviral drugs. In one study, HIV from 16% of such antiretroviral-naive individuals was shown to have a susceptibility to nonnucleoside rev...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.22.10269-10273.2000
更新日期:2000-11-01 00:00:00