Abstract:
:Mutations at amino acids 143, 148, and 155 in HIV-1 integrase (IN) define primary resistance pathways in subjects failing raltegravir (RAL)-containing treatments. Although each pathway appears to be genetically distinct, shifts in the predominant resistant virus population have been reported under continued drug pressure. To better understand this dynamic, we characterized the RAL susceptibility of 200 resistant viruses, and we performed sequential clonal analysis for selected cases. Patient viruses containing Y143R, Q148R, or Q148H mutations consistently exhibited larger reductions in RAL susceptibility than patient viruses containing N155H mutations. Sequential analyses of virus populations from three subjects revealed temporal shifts in subpopulations representing N155H, Y143R, or Q148H escape pathways. Evaluation of molecular clones isolated from different time points demonstrated that Y143R and Q148H variants exhibited larger reductions in RAL susceptibility and higher IN-mediated replication capacity (RC) than N155H variants within the same subject. Furthermore, shifts from the N155H pathway to either the Q148R or H pathway or the Y143R pathway were dependent on the amino acid substitution at position 148 and the secondary mutations in Y143R- or Q148R- or H-containing variants and correlated with reductions in RAL susceptibility and restorations in RC. Our observations in patient viruses were confirmed by analyzing site-directed mutations. In summary, viruses that acquire mutations defining the 143 or 148 escape pathways are less susceptible to RAL and exhibit greater RC than viruses containing 155 pathway mutations. These selective pressures result in the displacement of N155H variants by 143 or 148 variants under continued drug exposure.
journal_name
J Viroljournal_title
Journal of virologyauthors
Fransen S,Gupta S,Frantzell A,Petropoulos CJ,Huang Wdoi
10.1128/JVI.06618-11subject
Has Abstractpub_date
2012-07-01 00:00:00pages
7249-55issue
13eissn
0022-538Xissn
1098-5514pii
JVI.06618-11journal_volume
86pub_type
杂志文章abstract::Protective immunity to rotavirus (RV) is primarily mediated by antibodies produced by RV-specific memory B cells (RV-mBc). Of note, most of these cells express IgM, but the function of this subset is poorly understood. Here, using limiting dilution assays of highly sort-purified human IgM(+) mBc, we found that 62% and...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01466-12
更新日期:2012-10-01 00:00:00
abstract::The retinoblastoma tumor suppressor protein (pRb) can associate with the transforming proteins of several DNA tumor viruses, including the large T antigen encoded by polyomavirus (Py T Ag). Although pRb function is critical for regulating progression from G1 to S phase, a role for pRb in S phase has not been demonstra...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.4.3004-3013.1999
更新日期:1999-04-01 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
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01866-18
更新日期:2019-03-21 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.2.344-353.1987
更新日期:1987-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.26.2.243-248.1978
更新日期:1978-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.6.2585-2591.1989
更新日期:1989-06-01 00:00:00
abstract::MC159 is a viral FLIP (FLICE inhibitory protein) encoded by the molluscum contagiosum virus (MCV) enabling MCV to evade antiviral immunity and to establish persistent infections in humans. Here, we show that MC159 contains a functional SH3 binding motif, which mediates avid and selective binding to SH3BP4, a signaling...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01613-18
更新日期:2019-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.13.7138-7147.2004
更新日期:2004-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.4.2425-2432.1994
更新日期:1994-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.12.9567-9574.1998
更新日期:1998-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.9.5216-5225.1993
更新日期:1993-09-01 00:00:00
abstract::Inhibitors of hemagglutination by type A2 influenza virus and a recently isolated strain of type B influenza virus were separated by sucrose density gradient centrifugation and agarose gel filtration from horse serum. Using selected reagents, it was demonstrated that the active substituent on the horse serum inhibitor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.3.5.477-483.1969
更新日期:1969-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.12.10236-10244.1999
更新日期:1999-12-01 00:00:00
abstract::ZEBRA is an Epstein-Barr virus (EBV) transcriptional activator that mediates a genetic switch between the latent and lytic states of the virus by binding to the promoters of genes involved in lytic DNA replication and activating their transcription. A computer survey revealed that 9 of 23 potential or known ZEBRA-resp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.8.4803-4813.1992
更新日期:1992-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00813-12
更新日期:2012-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.31.3.621-629.1979
更新日期:1979-09-01 00:00:00
abstract::We have designed a ribozyme that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in U5 (at nucleotide +115). This ribozyme was tested in vitro and was found to give efficient and specific digestion of RNA containing the HIV-1 U5 sequence. When the U5 ribozyme was placed into the HIV-1 genome, virus replication...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.3.1432-1441.1992
更新日期:1992-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.1.182-194.1976
更新日期:1976-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2009-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02265-10
更新日期:2011-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00204-08
更新日期:2008-09-01 00:00:00
abstract::The chimpanzee monoclonal antibody (MAb) 5H2 is specific for dengue virus type 4 (DENV-4) and neutralizes the virus at a high titer in vitro. The epitope detected by the antibody was mapped by sequencing neutralization escape variants of the virus. One variant contained a Lys174-Glu substitution and another contained ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01420-07
更新日期:2007-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.40.1.65-77.1981
更新日期:1981-10-01 00:00:00
abstract:UNLABELLED:HIV-1-specific CD8 T cells can influence HIV-1 disease progression during untreated HIV-1 infection, but the functional and phenotypic properties of HIV-1-specific CD8 T cells in individuals treated with suppressive antiretroviral therapy remain less well understood. Here we show that a subgroup of HIV-1-spe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00789-15
更新日期:2015-08-01 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::A number of retrovirus-like sequences have been cloned from chimpanzee DNA which constitute the chimpanzee homologs of the endogenous colobus type C virus CPC-1. One of the clones contains a nearly complete viral genome, but others have sustained deletions of 1 to 2 kilobases in the polymerase gene. The pattern of rel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.43.3.914-924.1982
更新日期:1982-09-01 00:00:00
abstract::The Herpesviridae conserved infected-cell protein 27 (ICP27) is essential for cell culture-based replication of most herpesviruses studied. For members of the Alphaherpesvirinae, ICP27 regulates the expression of many viral genes, including expression of pUL44 (gC), pUL47 (VP13/14), and pUL48 (VP16). These three viral...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01903-18
更新日期:2019-02-05 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::The presence of porcine endogenous retroviruses presents a potential risk of transmission of infectious diseases (xenozoonosis) if tissues and organs from genetically modified pigs are to be used in xenotransplantation. Here, we report that intracellular expression of a llama single-domain antibody against p15, the ma...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.22.12132-12139.2003
更新日期:2003-11-01 00:00:00