Abstract:
:Transduction of the liver with single-stranded adeno-associated virus serotype 2 (AAV2) vectors is inefficient; less than 10% of hepatocytes are permissive for stable transduction, and transgene expression is characterized by a lag phase of up to 6 weeks. AAV2-based vector genomes packaged inside AAV6 or AAV8 capsids can transduce the liver with higher efficiency, but the molecular mechanisms underlying this phenomenon have not been determined. We now show that the primary barrier to transduction of the liver with vectors based on AAV2 capsids is uncoating of vector genomes in the nucleus. The majority of AAV2 genomes persist as encapsidated single-stranded molecules within the nucleus for as long as 6 weeks after vector administration. Double-stranded vector genomes packaged inside AAV2 capsids are at least 50-fold more active than single-stranded counterparts, but these vectors also exhibit a lag phase before maximal gene expression. Vector genomes packaged inside AAV6 or AAV8 capsids do not persist as encapsidated molecules and are more biologically active than vector genomes packaged inside AAV2 capsids. Our data suggest that the rate of uncoating of vector genomes determines the ability of complementary plus and minus single-stranded genomes to anneal together and convert to stable, biologically active double-stranded molecular forms.
journal_name
J Viroljournal_title
Journal of virologyauthors
Thomas CE,Storm TA,Huang Z,Kay MAdoi
10.1128/jvi.78.6.3110-3122.2004subject
Has Abstractpub_date
2004-03-01 00:00:00pages
3110-22issue
6eissn
0022-538Xissn
1098-5514journal_volume
78pub_type
杂志文章abstract::Poliovirus proteinase 2A (2Apro) is autocatalytically released from the viral polyprotein by cleavage in cis of a Tyr-Gly dipeptide at its own amino terminus, resulting in separation of the P1 structural and P2-P3 nonstructural protein precursors. A second Ty-Gly dipeptide within 3D polymerase is cleaved by 2Apro in t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.6.3330-3338.1992
更新日期:1992-06-01 00:00:00
abstract::Incubation of highly purified adeno-associated virus (AAV) capsids in vitro at pH 5.5 induced significant autocleavage of capsid proteins at several amino acid positions. No autocleavage was seen at pH 7.5. Examination of other AAV serotypes showed at least two different pH-induced cleavage patterns, suggesting that d...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01717-12
更新日期:2012-11-01 00:00:00
abstract::In some type C retroviruses, translation of the pol gene appears to require translational suppression of the proximal gag amber codon. To identify the region of the viral nucleic acid responsible for synthesis of the pol gene products, a 300-base-pair DNA fragment containing the stop codon from a type C murine virus (...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.10.3574-3580.1988
更新日期:1988-10-01 00:00:00
abstract::The envelope glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) is posttranslationally cleaved into two subunits. We show here that this endoproteolytic processing is not required for transport to the cell surface but is essential for LCMV GP to mediate infectivity of pseudotyped retroviral vectors. By sys...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.5.2866-2872.2003
更新日期:2003-03-01 00:00:00
abstract::Mengovirus 14S subviral protein particles generated in infected L cells and in a cell-free translation system primed with mengovirus RNA were purified by sucrose gradient centrifugation and immunoaffinity chromatography. The preparations from both sources contained essentially pure proteins epsilon, alpha, and gamma, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.1.275-284.1986
更新日期:1986-01-01 00:00:00
abstract::Apoptosis of infected cells is critically involved in antiviral defense. Apoptosis, however, may also support the release and spread of viruses. Although the elimination of infected hepatocytes is required to combat hepatitis B virus (HBV) infection, it is still unknown which consequences hepatocyte apoptosis has for ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00653-10
更新日期:2010-11-01 00:00:00
abstract::In view of the concern over potential infection hazards in the use of porcine tissues and organs for xenotransplantation to humans, we investigated the diversity of porcine endogenous retrovirus (PERV) genomes in the DNA of domestic pigs and related species. In addition to the three known envelope subgroups of infecti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.6.2771-2775.2001
更新日期:2001-03-01 00:00:00
abstract::Foxp3(+) CD4(+) regulatory T cells (Tregs) represent a highly suppressive T cell subset with well-characterized immunosuppressive effects during immune homeostasis and chronic infections, although the role of these cells in acute viral infections is poorly understood. The present study sought to examine the induction ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05685-11
更新日期:2012-03-01 00:00:00
abstract::The human T-cell leukemia virus type 1 (HTLV-1) transmembrane glycoprotein has a 24-amino-acid cytoplasmic domain whose function in the viral life cycle is poorly understood. We introduced premature-stop mutations and 18 single-amino-acid substitutions into this domain and studied their effects on cell-to-cell transmi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.9659-9663.1999
更新日期:1999-11-01 00:00:00
abstract::Mumps is a highly contagious human disease, characterized by lateral or bilateral nonsuppurative swelling of the parotid glands and neurological complications that can result in aseptic meningitis or encephalitis. A mumps vaccination program implemented since the 1960s reduced mumps incidence by more than 99% and kept...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02778-13
更新日期:2014-03-01 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::Defined segments of the transmembrane envelope glycoprotein (gp45) of equine infectious anemia virus were expressed as TrpLE fusion proteins and examined for their reactivity in Western immunoblots against a diverse panel of equine immune sera. The most immunogenic region of gp45 was localized to its amino terminus, p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.2.1013-1018.1991
更新日期:1991-02-01 00:00:00
abstract::We have previously shown that the herpes simplex virus immediate-early regulatory protein ICP27 acts posttranscriptionally to affect mRNA processing (R. M. Sandri-Goldin and G. E. Mendoza, Genes Dev. 6:848-863, 1992). Specifically, in the presence of ICP27, spliced target mRNAs were decreased 5- to 10-fold in transfec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.8.4797-4810.1994
更新日期:1994-08-01 00:00:00
abstract::Interferon (IFN) is an important immune system molecule capable of inducing an antiviral state within cells. Herpes simplex virus type 1 (HSV-1) replication is somewhat reduced in tissue culture in the presence of IFN, presumably due to decreased viral transcription. Here, we show mutations that inactivate immediate-e...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.4.2052-2056.2000
更新日期:2000-02-01 00:00:00
abstract:UNLABELLED:The accessory gene vpr, common to all primate lentiviruses, induces potent G2/M arrest in cycling cells. A recent study showed that human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) mediates this through activation of the SLX4/MUS81/EME1 exonuclease complex that forms part of the Fanconi anem...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02307-14
更新日期:2015-01-01 00:00:00
abstract::A mutant of herpes simplex virus type 1 (HSV-1) in which glycoprotein H (gH) coding sequences were deleted and replaced by the Escherichia coli lacZ gene under the control of the human cytomegalovirus IE-1 gene promoter was constructed. The mutant was propagated in Vero cells which contained multiple copies of the HSV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.1.341-348.1992
更新日期:1992-01-01 00:00:00
abstract:UNLABELLED:In vitro, infection of polarized human intestinal epithelial cells by coxsackievirus B3 (CVB3) depends on virus interaction with decay-accelerating factor (DAF), a receptor expressed on the apical cell surface. Although mice are highly susceptible to CVB3 infection when virus is delivered by intraperitoneal ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03468-14
更新日期:2015-04-01 00:00:00
abstract::Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the matern...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01905-16
更新日期:2017-01-31 00:00:00
abstract::We analyzed capsomeres of human papillomavirus type 16 (HPV16) consisting of the L1 major structural protein for their ability to trigger a cytotoxic T-cell (CTL) response. To this end, we immunized C57BL/6 mice and used the L1(165-173) peptide for ex vivo restimulation of splenocytes prior to analysis ((51)Cr release...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.8.4635-4645.2003
更新日期:2003-04-01 00:00:00
abstract:UNLABELLED:Retargeting of gammaretroviral envelope proteins has shown promising results in the isolation of novel isolates with therapeutic potential. However, the optimal conditions required to obtain high-affinity retargeted envelope proteins with narrow tropism are not understood. This study highlights the advantage...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02544-15
更新日期:2015-12-30 00:00:00
abstract::Normal replication of Moloney murine leukemia virus (MoMLV) requires the integration of a DNA copy of the viral RNA genome into a chromosome of the host. In this work, we characterize the DNA sequences at the ends of the linear proviral precursor that are required for integration in the presence of MoMLV integration p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.11.5645-5648.1990
更新日期:1990-11-01 00:00:00
abstract::Synthetic peptides containing portions of a highly conserved region of retroviral transmembrane proteins of human and animal retroviruses were tested for their ability to inhibit lymphoproliferation to determine the minimum amino acid sequence required. The previously reported immunosuppression mediated by the peptide...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.8.3250-3256.1989
更新日期:1989-08-01 00:00:00
abstract::Interspecies transmission of the transmissible spongiform encephalopathies (TSEs), or prion diseases, can result in the adaptation and selection of TSE strains with an expanded host range and increased virulence such as in the case of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease. To investiga...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.12.5542-5547.2000
更新日期:2000-06-01 00:00:00
abstract::Nearly 50 years ago, the discovery of interferon prompted the notion that host cells innately respond to viral invasion. Since that time, technological advances have allowed this response to be extensively characterized and dissected in vitro. However, these advances have only recently been applied to highly complex, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01936-06
更新日期:2007-02-01 00:00:00
abstract::The antigenic binding sites of two monoclonal antibodies are located in the COOH-terminal region (clone 412) and probably in an internal region (clone 7) of simian virus 40 large T antigen. A third monoclonal antibody (clone 122), which has been shown to bind nonviral T antigen, does not react with HeLa cells infected...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.1.478-482.1981
更新日期:1981-01-01 00:00:00
abstract::Physiological microenvironments such as blood, seminal plasma, mucosal secretions, or lymphatic fluids may influence the biology of the virus-host cell and immune interactions for human immunodeficiency virus type 1 (HIV-1). Relative to media, physiological levels of human plasma were found to enhance the infectivity ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.10.6054-6062.1995
更新日期:1995-10-01 00:00:00
abstract::Three late transcripts have been mapped to the vaccinia virus 7.1-kilobase (kb) EcoRI F fragment, which is located approximately 85 kb from the left end of the viral genome. Hybrid selection and translation of RNA have demonstrated that these mRNAs encode three polypeptides with apparent molecular weights of 32,000 (3...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.2.510-520.1984
更新日期:1984-02-01 00:00:00
abstract::Monoclonal antibodies (MAbs) directed against the E2 glycoprotein of mouse hepatitis virus (MHV) have been classified according to their ability to bind to either of the two purified 90,000-molecular-weight subunits (90K subunits) of the 180K peplomeric glycoprotein E2. Correlation with previously reported information...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.6.3051-3055.1990
更新日期:1990-06-01 00:00:00
abstract::All plus-strand RNA viruses encode an RNA-dependent RNA polymerase (RdRp) that functions as the catalytic subunit of the viral replication/transcription complex, directing viral RNA synthesis in concert with other viral proteins and, sometimes, host proteins. RNA synthesis essentially can be initiated by two different...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00564-07
更新日期:2007-08-01 00:00:00
abstract::The subgroup A to E avian sarcoma and leukosis viruses (ASLVs) are highly related and are thought to have evolved from a common ancestor. These viruses use distinct cell surface proteins as receptors to gain entry into avian cells. Chickens have evolved resistance to infection by the ASLVs. We have identified the muta...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.24.13489-13500.2004
更新日期:2004-12-01 00:00:00