Abstract:
:ABT-378, a new human immunodeficiency virus type 1 (HIV-1) protease inhibitor which is significantly more active than ritonavir in cell culture, is currently under investigation for the treatment of AIDS. Development of viral resistance to ABT-378 in vitro was studied by serial passage of HIV-1 (pNL4-3) in MT-4 cells. Selection of viral variants with increasing concentrations of ABT-378 revealed a sequential appearance of mutations in the protease gene: I84V-L10F-M46I-T91S-V32I-I47V. Further selection at a 3.0 microM inhibitor concentration resulted in an additional change at residue 47 (V47A), as well as reversion at residue 32 back to the wild-type sequence. The 50% effective concentration of ABT-378 against passaged virus containing these additional changes was 338-fold higher than that against wild-type virus. In addition to changes in the protease gene, sequence analysis of passaged virus revealed mutations in the p1/p6 (P1' residue Leu to Phe) and p7/p1 (P2 residue Ala to Val) gag proteolytic processing sites. The p1/p6 mutation appeared in several clones derived from early passages and was present in all clones obtained from passage P11 (0.42 microM ABT-378) onward. The p7/p1 mutation appeared very late during the selection process and was strongly associated with the emergence of the additional change at residue 47 (V47A) and the reversion at residue 32 back to the wild-type sequence. Furthermore, this p7/p1 mutation was present in all clones obtained from passage P17 (3.0 microM ABT-378) onward and always occurred in conjunction with the p1/p6 mutation. Full-length molecular clones containing protease mutations observed very late during the selection process were constructed and found to be viable only in the presence of both the p7/p1 and p1/p6 cleavage-site mutations. This suggests that mutation of these gag proteolytic cleavage sites is required for the growth of highly resistant HIV-1 selected by ABT-378 and supports recent work demonstrating that mutations in the p7/p1/p6 region play an important role in conferring resistance to protease inhibitors (L. Doyon et al., J. Virol. 70:3763-3769, 1996; Y. M. Zhang et al., J. Virol. 71:6662-6670, 1997).
journal_name
J Viroljournal_title
Journal of virologyauthors
Carrillo A,Stewart KD,Sham HL,Norbeck DW,Kohlbrenner WE,Leonard JM,Kempf DJ,Molla Adoi
10.1128/JVI.72.9.7532-7541.1998subject
Has Abstractpub_date
1998-09-01 00:00:00pages
7532-41issue
9eissn
0022-538Xissn
1098-5514journal_volume
72pub_type
杂志文章abstract::Extracts from nodavirus-infected Drosophila cells contained detergent-labile 140S "young" particles much richer than mature virions in their content of protein alpha, a precursor of coat proteins beta and gamma. Incorporation studies in infected cells showed that most newly synthesized alpha protein was assembled into...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3399-3406.1988
更新日期:1988-09-01 00:00:00
abstract::H5N1 highly pathogenic avian influenza virus (HPAIV) has continued to spread and poses a significant threat to both animal and human health. Current influenza vaccine strategies have limitations that prevent their effective use for widespread inoculation of animals in the field. Vaccine strains of Newcastle disease vi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01514-06
更新日期:2007-01-01 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 HIV-1 Rev response element (RRE) is a 351-base element in unspliced and partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), one branched domain (domain II)...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00746-17
更新日期:2017-10-13 00:00:00
abstract::Stress signaling from mitochondria and the endoplasmic reticulum (ER) leads to the induction of the proapoptotic transcription factor CHOP/GADD153. Many viruses use the ER as a site of replication and/or envelopment, and this activity can lead to the activation of ER stress and apoptosis. African swine fever virus (AS...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.19.10825-10828.2004
更新日期:2004-10-01 00:00:00
abstract::Although the envelope gene of human immunodeficiency virus type 1 shows considerable strain variability, cysteine residues of the envelope protein are strongly conserved, suggesting that they are important to the envelope structure. We constructed and analyzed mutants of a biologically active molecular clone of human ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2250-2259.1990
更新日期:1990-05-01 00:00:00
abstract::The mutational alterations in polyoma virus mutants ts-a and ts-25E which cause their large T-antigens to be thermolabile have been identified. In ts-a, a G leads to A transition at nucleotide 2193 causes the replacement of Ala (GCT) by Thr (ACT). In ts-25E, a G leads to T transversion at nucleotide 2883 causes the re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.3.1094-1098.1981
更新日期:1981-03-01 00:00:00
abstract::Treatment of influenza virus and its purified hemagglutining with glycosidases from Diplococcus pneumoniae, which included beta-galactosidase, beta-N-acetylglucosminidase, and endoglycosidase D, released amino and neutral sugars from the virus and these as well as large oligosaccharides from the purified hemagglutinin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.27.1.164-171.1978
更新日期:1978-07-01 00:00:00
abstract::Engineered alphavirus vectors expressing reporters of infection have been used for a number of years due to their relatively low costs for analysis of virus replication and the capacity to utilize imaging systems for longitudinal measurements of growth within single animals. In general, these vectors have been derived...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02990-13
更新日期:2014-02-01 00:00:00
abstract::Examination of the interaction between human immunodeficiency virus (HIV) regulatory gene products and the host immune system is fundamental to understanding the pathogenesis of HIV and could reveal possible targets for therapeutic intervention in the treatment of AIDS. The HIV Tat gene is a potential candidate for th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.12.7622-7629.1995
更新日期:1995-12-01 00:00:00
abstract::Only a few archaeal viruses have been subjected to detailed structural analyses. Major obstacles have been the extreme conditions such as high salinity or temperature needed for the propagation of these viruses. In addition, unusual morphotypes of many archaeal viruses have made it difficult to obtain further informat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01347-09
更新日期:2010-01-01 00:00:00
abstract::Assembly and maturation of retroviral particles requires the aggregation and controlled proteolytic cleavage of polyprotein core precursors by a precursor-encoded protease (PR). Active, mature retroviral PR is a dimer, and the accumulation of precursors at sites of assembly may facilitate subunit interaction and subse...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.11.6165-6172.1991
更新日期:1991-11-01 00:00:00
abstract::Discovery of genetically distinct hantaviruses in multiple species of shrews (order Soricomorpha, family Soricidae) and moles (family Talpidae) contests the conventional view that rodents (order Rodentia, families Muridae and Cricetidae) are the principal reservoir hosts and suggests that the evolutionary history of h...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02450-10
更新日期:2011-08-01 00:00:00
abstract::Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers of preformed nucleocapsids, but their biological significance has been debated, and they have been suggested to be aggregates of viral proteins without any further biological function. However, recent data for o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01525-12
更新日期:2012-11-01 00:00:00
abstract::Interferons (IFNs) are a critical component of the first line of antiviral defense. The activation of Toll-like receptors (TLRs) expressed by dendritic cells triggers different signaling cascades that result in the production of large amounts of IFNs. However, the functional consequences of TLR activation and differen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01956-12
更新日期:2013-03-01 00:00:00
abstract::Cell surface receptors exploited by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) for infection are major determinants of tropism. HIV-1 usually requires two receptors to infect cells. Gp120 on HIV-1 virions binds CD4 on the cell surface, triggering conformational rearrangements that creat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.9.7795-7804.1999
更新日期:1999-09-01 00:00:00
abstract::Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus and one of the most common agents of viral encephalitis. The infectious entry process of JEV into host cells remains largely unknown. Here, we present a systemic study concerning the cellular entry mechanism of JEV to B104 rat neuroblastoma cells. It was...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00903-12
更新日期:2012-12-01 00:00:00
abstract::Human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription from the long terminal repeats (LTR). Mechanisms through which Tax activates LTR have been established, but coactivators of this process remain to be identified and characterized. Here we show that all three members of the TORC famil...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00103-06
更新日期:2006-07-01 00:00:00
abstract::Regulation of immediate-early gene expression in human cytomegalovirus is subject to complex controls. The major immediate-early (mIE) gene is regulated by both positive and negative regulatory signals, including autoregulation mediated by a cis-repressive sequence. A second immediate-early gene, the US3 gene, is tran...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5362-5367.1995
更新日期:1995-09-01 00:00:00
abstract::A region of the herpesvirus saimiri genome encoding an mRNA with two open reading frames (ORFs) has been identified to be essential for transformation of T cells. Deletion of either ORF resulted in the loss of transforming ability. ORF-1 has been shown to code for a collagen-like oncoprotein. This study shows for the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.7.4495-4499.1995
更新日期:1995-07-01 00:00:00
abstract::The human immunodeficiency virus (HIV) and the closely related simian immunodeficiency virus (SIV) induce profound immune dysfunction in primate species. The present studies show that cell populations infected in vitro with SIV exhibit increases in major histocompatibility complex (MHC) class II antigen expression. Ce...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.5.1421-1426.1987
更新日期:1987-05-01 00:00:00
abstract::The Epstein-Barr virus nuclear antigen 2 (EBNA-2) acidic domain is essential for B-lymphocyte growth transformation and can activate transcription when brought to a promoter by a sequence-specific DNA-binding domain. We now show that the EBNA-2 acidic domain has slightly less activity than the proteotypic acidic trans...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.1.585-588.1995
更新日期:1995-01-01 00:00:00
abstract::Infection of human dermal microvascular endothelial (HMVEC-d) cells and human foreskin fibroblast (HFF) cells in vitro by Kaposi's sarcoma-associated herpesvirus (KSHV) provides an excellent in vitro model system to study viral latency. KSHV infection is characterized by the induction of preexisting host signal cascad...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00231-06
更新日期:2006-07-01 00:00:00
abstract::When mouse L cells are infected for 22 hr with vesicular stomatitis virus (VSV), a ribonucleic acid-containing enveloped virus, greater than 70% of the major histocompatibility antigen (H-2), is no longer detectable by the method of inhibition of immune cytolysis. Infected cells prelabeled with (14)C-glucosamine also ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.10.4.578-585.1972
更新日期:1972-10-01 00:00:00
abstract::The existence of novel endogenous retrovirus elements in the chicken genome, designated EAV-HP, with close sequence identity to the env gene of avian leukosis virus (ALV) subgroup J has been reported (L. M. Smith, A. A. Toye, K. Howes, N. Bumstead, L. N. Payne, and K. Venugopal, J. Gen. Virol. 80:261-268, 1999). To re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.3.1296-1306.2000
更新日期:2000-02-01 00:00:00
abstract::The Cas-Br-E murine leukemia virus is a nondefective retrovirus that induces non-T-, non-B-cell lymphomas in susceptible NIH/Swiss mice. By using a DNA probe derived from Cas-Br-E provirus-flanking sequences, we identified a DNA region, originally called Sic-1, rearranged in 16 of 24 tumors analyzed (67%). All proviru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.1.7-15.1991
更新日期:1991-01-01 00:00:00
abstract::We constructed a matched set of plasmids to investigate the interactions of essential core sequences of the simian virus 40 replication origin with flanking regulatory sequences. Deletions of either T-antigen-binding region I or the 21-base-pair repeated promoter elements reduced replication to 50 to 70% of wild-type ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.1.138-144.1986
更新日期:1986-01-01 00:00:00
abstract:UNLABELLED:Human cytomegalovirus (HCMV) is a major cause of morbidity and mortality in transplant patients and is the leading viral cause of birth defects after congenital infection. HCMV infection relies on the recognition of cell-specific receptors by one of the viral envelope glycoprotein complexes. Either the gH/gL...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02517-15
更新日期:2016-04-29 00:00:00
abstract::Little is known about the mechanisms used by enveloped viruses to separate themselves from the cell surface at the final step of budding. However, small sequences in the Gag proteins of several retroviruses (L domains) have been implicated in this process. A sequence has been identified in the M proteins of rhabdoviru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.4.3359-3365.1999
更新日期:1999-04-01 00:00:00
abstract::To assess the heterogeneity of cytotoxic T lymphocytes (CTLs) directed against viral epitopes, we studied six class I major histocompatibility complex-restricted (H-2Db) CTL clones that recognize the same 9-amino-acid immunodominant epitope, amino acids 278 to 286 from envelope glycoprotein 2 (GP2) of lymphocytic chor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.1845-1851.1989
更新日期:1989-05-01 00:00:00