Abstract:
:Integration of viral DNA into the host chromosome is an essential step in the life cycle of retroviruses and is facilitated by the viral integrase enzyme. The first generation of integrase inhibitors recently approved or currently in late-stage clinical trials shows great promise for the treatment of human immunodeficiency virus (HIV) infection, but virus is expected to develop resistance to these drugs. Therefore, we used a novel resistance selection protocol to follow the emergence of resistant HIV in the presence of the integrase inhibitor elvitegravir (GS-9137). We find the primary resistance-conferring mutations to be Q148R, E92Q, and T66I and demonstrate that they confer a reduction in susceptibility not only to elvitegravir but also to raltegravir (MK-0518) and other integrase inhibitors. The locations of the mutations are highlighted in the catalytic sites of integrase, and we correlate the mutations with expected drug-protein contacts. In addition, mutations that do not confer reduced susceptibility when present alone (H114Y, L74M, R20K, A128T, E138K, and S230R) are also discussed in relation to their position in the catalytic core domain and their proximity to known structural features of integrase. These data broaden the understanding of antiviral resistance against integrase inhibitors and may give insight facilitating the discovery of second-generation compounds.
journal_name
J Viroljournal_title
Journal of virologyauthors
Goethals O,Clayton R,Van Ginderen M,Vereycken I,Wagemans E,Geluykens P,Dockx K,Strijbos R,Smits V,Vos A,Meersseman G,Jochmans D,Vermeire K,Schols D,Hallenberger S,Hertogs Kdoi
10.1128/JVI.00470-08subject
Has Abstractpub_date
2008-11-01 00:00:00pages
10366-74issue
21eissn
0022-538Xissn
1098-5514pii
JVI.00470-08journal_volume
82pub_type
杂志文章abstract::Cell extracts from murine A9 or human HeLa cells containing wild-type copies the NS1 polypeptide of minute virus of mice (MVM), produced from a recombinant vaccinia virus, can support the resolution of viral 3' termini from palindromic junction fragments of dimeric, replicative-form MVM DNA. Resolution resulted in the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.3.1579-1589.1993
更新日期:1993-03-01 00:00:00
abstract::Virus-specific RNA synthesized in monkey cells after infection by both wild-type simian virus 40 (SV40) and the early SV40 temperature-sensitive mutant tsA58 has been analyzed. The fraction of SV40-specific RNA increased throughout infection with either wild-type SV40 or with tsA58 in direct proportion to the accumula...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.23.1.167-176.1977
更新日期:1977-07-01 00:00:00
abstract::Here, we report a novel porcine circovirus type 2a (PCV2a) strain with 11 nucleotides (nt) inserted in the origin of genome replication (Ori). This is the first report of a PCV2a strain with nucleotide insertion in Ori. Our study will help further epidemiological studies and extend our knowledge of evolutionary charac...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00760-12
更新日期:2012-06-01 00:00:00
abstract::Klebsiella pneumoniae MirM7 is a wild-type strain which grows as cocci at pH 7 and above and as rods at pH 6.5 and below. Cultures of this strain and an auxotrophic derivative, MirM7b, have been found to undergo spontaneous lysis after purification from possible contaminating viruses. Lysates always contained two phag...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.28.3.772-785.1978
更新日期:1978-12-01 00:00:00
abstract::We present data that retroviral gene expression in early hematopoietic cells is subjected to transcriptional controls similar to those previously described for embryonic stem cells. Transient transfection experiments revealed that both the viral enhancer region in the U3 region of the long terminal repeat as well as a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.12.7541-7547.1995
更新日期:1995-12-01 00:00:00
abstract::The recent increase in human cases of influenza A H3N2 variant virus [A(H3N2)v] highlights the need to assess whether seasonal influenza vaccination provides cross-protection against A(H3N2)v virus. Our data demonstrate that the 2011-2012 trivalent inactivated influenza vaccine (TIV) protected ferrets against homologo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02625-12
更新日期:2013-01-01 00:00:00
abstract::Nonenveloped viral capsids are metastable structures that undergo conformational changes during virus entry that lead to interactions of the capsid or capsid fragments with the cell membrane. For members of the Caliciviridae, neither the nature of these structural changes in the capsid nor the factor(s) responsible fo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02371-09
更新日期:2010-06-01 00:00:00
abstract::The origin and role of the endonuclease activity associated with purified virions of simian virus 40, previously described by this and other laboratories, have been further investigated. We found that the enzymatic activity from virions of temperature-sensitive (ts) mutants is not more heat labile than that from wild-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.17.2.352-362.1976
更新日期:1976-02-01 00:00:00
abstract::To reliably infect a primate model for human immunodeficiency virus (HIV), approximately 10,000-fold more virus must be delivered vaginally than intravenously. However, the vaginal mechanisms that help protect against HIV are poorly understood. Here, we report that human cervicovaginal mucus (CVM), obtained from donor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01899-08
更新日期:2009-11-01 00:00:00
abstract::The simian B-lymphotropic papovavirus (LPV) encodes a large tumor antigen (T antigen) which is 45% identical to both the simian virus 40 (SV40) and the polyomavirus (PyV) large T antigens. In transgenic mice, the transforming properties of the LPV T antigen are similar to those of the SV40 T antigen. However, little i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.10.5417-5424.1991
更新日期:1991-10-01 00:00:00
abstract::PM2 DNA was prepared with different superhelical densities (sigma) in order to examine the relationship betweenn supercoiling and the occurrence of a region(s) of unpaired bases in this DNA. A previous study showed that CH3HgOH reacts with native superhelical PM2 DNA more rapidly than the nicked form II. This evaluati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.1.195-204.1976
更新日期:1976-04-01 00:00:00
abstract::Influenza viruses often evade host immunity via antigenic drift and shift despite previous influenza virus infection and/or vaccination. Vaccines that match circulating virus strains are needed for optimal protection. Development of a universal influenza virus vaccine providing broadly cross-protective immunity will b...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00120-13
更新日期:2013-05-01 00:00:00
abstract::Breast cancer is the second leading cause of cancer-related deaths in women in the United States. Triple-negative breast cancer constitutes a subset of breast cancer that is associated with higher rates of relapse, decreased survival, and limited therapeutic options for patients afflicted with this type of breast canc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01411-19
更新日期:2019-11-13 00:00:00
abstract::Viral recombination has been postulated to play two roles in the development of human immunodeficiency virus (HIV) resistance to antiretroviral drugs. First, recombination has the capacity to associate resistance mutations expressed by distinct viruses, thereby contributing to the development of viruses with improved ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00083-07
更新日期:2007-07-01 00:00:00
abstract::Development of a vaccine for the common cold has been thwarted by the fact that there are more than 100 serotypes of human rhinovirus (HRV). We previously demonstrated that the HRV14 capsid is dynamic and transiently displays the buried N termini of viral protein 1 (VP1) and VP4. Here, further evidence for this "breat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00557-09
更新日期:2009-07-01 00:00:00
abstract::Alphavirus infection of fibroblastic cell types in vitro inhibits host cell translation and transcription, leading to suppression of interferon alpha/beta (IFN-α/β) production. However, the effect of infection upon myeloid cells, which are often the first cells encountered by alphaviruses in vivo, is unclear. Previous...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00872-19
更新日期:2019-11-26 00:00:00
abstract::Transcriptional stimulatory properties of virus-encoded transactivators appear to be critical for viral gene expression and may be linked to cellular transformation in certain cases. Recently, the simian virus 40 (SV40) 17-kDa small-t antigen was shown to stimulate transcription of polymerase II and III genes in trans...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.12.6553-6561.1991
更新日期:1991-12-01 00:00:00
abstract::The sequences of several hundred nucleotides around the junctions between the L and S components in concatemeric DNA and in mature virion DNA were ascertained. The two ends of the mature genome (which are joined in concatemeric DNA) show no sequence homology. Several directly repeated elements are present near both en...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.10.4968-4977.1990
更新日期:1990-10-01 00:00:00
abstract::Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) binds complement component C3b and protects virus from complement-mediated neutralization. Differences in complement interacting domains exist between gC of HSV-1 (gC1) and HSV-2 (gC2), since the amino terminus of gC1 blocks complement C5 fr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.8.4038-4046.2006
更新日期:2006-04-01 00:00:00
abstract::The secreted cytokine alpha/beta interferon (IFN-alpha/beta) binds its receptor to activate the Jak-STAT signal transduction pathway, leading to formation of the heterotrimeric IFN-stimulated gene factor 3 (ISGF3) transcription complex for induction of IFN-stimulated genes (ISGs) and establishment of an antiviral stat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01787-08
更新日期:2009-03-01 00:00:00
abstract:UNLABELLED:The HIV-1 virion infectivity factor (Vif) targets the cellular cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) for degradation via the host ubiquitin-proteasome pathway. Vif recruits a cellular E3 ubiquitin ligase to polyubiquitinate A3G/F. The activity of Vif critically depends on the cellular core bi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03824-13
更新日期:2014-03-01 00:00:00
abstract::Vaccinia virus genes are expressed in a sequential fashion, suggesting a role for negative as well as positive regulatory mechanisms. A potential down regulator of gene expression was mapped by transfection assays to vaccinia virus open reading frame D10, which encodes a protein with no previously known function. Inhi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.1.791-796.1999
更新日期:1999-01-01 00:00:00
abstract::The immediate-early gene ie2 of murine cytomegalovirus was characterized. The 1.75-kb ie2 transcript is spliced from three exons, of 78, 124, and 1,283 nucleotides, which are separated by introns of 1,245 and 364 nucleotides. An ATG codon located in the third exon leads into an open reading frame of 391 codons. Immedi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.3.1638-1643.1991
更新日期:1991-03-01 00:00:00
abstract::We have presented a new approach to studying bacteriophage T4 head maturation. Using a modified M-band technique, we have shown that progeny deoxyribonucleic acid (DNA) was synthesized on the host cell membrane throughout infection. This DNA was released from the membrane later in infection as the result of formation ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.11.3.359-367.1973
更新日期:1973-03-01 00:00:00
abstract::The influenza A virus (IAV) envelope protein hemagglutinin binds α2,6- or α2,3-linked sialic acid as a host cell receptor. Bat IAV subtypes H17N10 and H18N11 form an exception to this rule and do not bind sialic acid but enter cells via major histocompatibility complex (MHC) class II. Here, we review current knowledge...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.01357-19
更新日期:2020-01-31 00:00:00
abstract::Herpesvirus saimiri (HVS) is a T-cell-specific transforming and oncogenic virus. A protein encoded by HVS known as Tip-484 (for tyrosine kinase interacting protein from HVS strain 484) is required for this transformation. Tip-484 binds specifically to the nonreceptor protein tyrosine kinase p56lck. By transfecting Tip...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.1.378-382.1997
更新日期:1997-01-01 00:00:00
abstract:UNLABELLED:The HIV-1 glycoprotein 41 promotes fusion of the viral membrane with that of the target cell. Structural, biochemical, and biophysical studies suggest that its membrane-proximal external region (MPER) may interact with the HIV-1 membrane and induce its disruption and/or deformation during the process. Howeve...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02151-14
更新日期:2014-11-01 00:00:00
abstract::Storage of the dimeric (alphabeta) form of avian myeloblastosis virus (AMV) DNA polymerase in glycerol resulted in the release of the smaller alpha subunit, as detected by glycerol gradient sedimentation. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of enzyme stored in glycerol showed the conc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.3.904-910.1976
更新日期:1976-06-01 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::We have determined the complete nucleotide sequence of an infectious cloned genome of ground squirrel hepatitis virus (GSHV), a nonpathogenic member of the hepadnavirus group. The genome is 3,311 base pairs long and contains the major open reading frames described for the related human and woodchuck hepatitis B viruse...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.51.2.367-375.1984
更新日期:1984-08-01 00:00:00