Abstract:
BACKGROUND:Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful antiretroviral therapy (ART) in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV). Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Deltanef were treated with the reverse transcriptase (RT) inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. RESULTS:Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Deltanef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Deltanef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4+ T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Deltanef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8+ T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055. CONCLUSION:These results support the concept that anti-viral immunity acts synergistically with ART to augment drug efficacy by suppressing replication of viral variants with reduced drug sensitivity. Treatment strategies that seek to combine immunotherapeutic intervention as an adjunct to antiretroviral drugs may therefore confer added benefit by controlling replication of HIV-1, and reducing the likelihood of treatment failure due to the emergence of drug-resistant virus, thereby preserving treatment options.
journal_name
Retrovirologyjournal_title
Retrovirologyauthors
Metzner KJ,Binley JM,Gettie A,Marx P,Nixon DF,Connor RIdoi
10.1186/1742-4690-3-97subject
Has Abstractpub_date
2006-12-21 00:00:00pages
97issn
1742-4690pii
1742-4690-3-97journal_volume
3pub_type
杂志文章相关文献
Retrovirology文献大全abstract:BACKGROUND:HIV-1 capsid influences viral uncoating and nuclear import. Some capsid is detected in the nucleus but it is unclear if it has any function. We reported that the antibiotic Coumermycin-A1 (C-A1) inhibits HIV-1 integration and that a capsid mutation confers resistance to C-A1, suggesting that capsid might aff...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-016-0262-0
更新日期:2016-04-23 00:00:00
abstract:BACKGROUND:Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, there is an association between HTLV-1 tax subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. To investigate the role of HTLV-1 subgroups in viral pathogenesis, we studied the functional difference i...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-018-0454-x
更新日期:2018-11-06 00:00:00
abstract:BACKGROUND:Retroviruses have a diploid genome and recombine at high frequency. Recombinant proviruses can be generated when two genetically different RNA genomes are packaged into the same retroviral particle. It was shown in several studies that recombinant proviruses could be generated in each round of HIV-1 replicat...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-2-3
更新日期:2005-01-18 00:00:00
abstract:BACKGROUND:Combination anti-viral therapies have reduced treatment failure rates by requiring multiple specific mutations to be selected on the same viral genome to impart high-level drug resistance. To determine if the common protease inhibitor resistance mutation L90M is only selected once or repeatedly on different ...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-5-7
更新日期:2008-01-25 00:00:00
abstract:BACKGROUND:The 18 residue tail abutting the SH3 fold that comprises the heart of the C-terminal domain is the only part of HIV-1 integrase yet to be visualized by structural biology. To ascertain the role of the tail region in integrase function and HIV-1 replication, a set of deletion mutants that successively lacked ...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-6-94
更新日期:2009-10-19 00:00:00
abstract:BACKGROUND:The foamy viral genome encodes four central purine-rich elements localized in the integrase-coding region of pol. Previously, we have shown that the first two of these RNA elements (A and B) are required for protease dimerization and activation. The D element functions as internal polypurine tract during rev...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-017-0337-6
更新日期:2017-02-06 00:00:00
abstract::In the mid-1990's, researchers hypothesized, based on new viral load data, that HIV-1 causes CD4+ T-cell depletion by direct cytopathic effect. New data from non-human primate studies has raised doubts about this model of HIV-1 pathogenesis. Despite having high levels of viremia, most SIV infections are well tolerated...
journal_title:Retrovirology
pub_type: 社论
doi:10.1186/1742-4690-3-60
更新日期:2006-09-08 00:00:00
abstract:BACKGROUND:A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV chall...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-11-8
更新日期:2014-01-20 00:00:00
abstract::Friends and colleagues remember John N. Brady, Ph.D., Chief of the Virus Tumor Biology Section of the Laboratory of Cellular Oncology, who died much too young at the age of 57 on April 27, 2009 of colon cancer. John grew up in Illinois and received his Ph.D. with Dr. Richard Consigli at Kansas State University studyin...
journal_title:Retrovirology
pub_type: 传,社论,历史文章
doi:10.1186/1742-4690-6-48
更新日期:2009-05-19 00:00:00
abstract:BACKGROUND:Several factors determine the risk of HIV mother-to-child transmission (MTCT), such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Chagas' disease is one of the most endemic zoonoses in Latin America, caused by the protozoan Trypanosoma cruzi. The purpose of the study was to d...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-5-53
更新日期:2008-07-01 00:00:00
abstract:BACKGROUND:HIV-1 Nef is a multifunctional protein required for full pathogenicity of the virus. As Nef has no known enzymatic activity, it necessarily functions through protein-protein interaction interfaces. A critical Nef protein interaction interface is centered on its polyproline segment (P69VRPQVPLRP78) which cont...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-9-47
更新日期:2012-05-31 00:00:00
abstract::The development of safe and effective combination antiretroviral therapies for human immunodeficiency virus (HIV) infection over the past several decades has significantly reduced HIV-associated morbidity and mortality. Additionally, antiretroviral drugs have provided an effective means of protection against HIV trans...
journal_title:Retrovirology
pub_type: 杂志文章,评审
doi:10.1186/s12977-020-00515-3
更新日期:2020-04-10 00:00:00
abstract:BACKGROUND:Mutations in the substrate of HIV-1 protease, especially changes in the NC/p1 cleavage site, can directly contribute to protease inhibitor (PI) resistance and also compensate for defects in viral replicative capacity (RC) due to a drug resistant protease. These NC/p1 changes are known to enhance processing o...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-9-29
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosp...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-2-63
更新日期:2005-10-18 00:00:00
abstract:BACKGROUND:Chemokine receptors (CKRs), the primordial receptors for primate lentiviruses, are sufficient to mediate virus-cell fusion. Several different fusogenic CKRs and related receptors provide a broad potential host cell range, presumably advantageous for viral spread within a given infected individual, and across...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-9-61
更新日期:2012-07-25 00:00:00
abstract:BACKGROUND:We have previously reported that CD4 T cells from some exposed uninfected (EU) Vietnamese intravenous drug users are relatively resistant to HIV infection in vitro. Here, we further characterized the restriction of viral replication in CD4 T cells from five EUs and assessed its persistence in serial samples....
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-3-81
更新日期:2006-11-08 00:00:00
abstract:BACKGROUND:Mammalian cells harbour RNA quality control and degradative machineries such as nonsense-mediated mRNA decay that target cellular mRNAs for clearance from the cell to avoid aberrant gene expression. The role of the host mRNA decay pathways in macrophages in the context of human immunodeficiency virus type 1 ...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-019-0465-2
更新日期:2019-02-07 00:00:00
abstract:BACKGROUND:Extra-cellular roles of Tat might be the main cause of maintenance of HIV-1 infected CD4 T cells or reservoir cells. We developed a synthetic vaccine based on a Tat variant of 101 residues called Tat Oyi, which was identified in HIV infected patients in Africa who did not progress to AIDS. We compared, using...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-3-8
更新日期:2006-01-27 00:00:00
abstract::The glycan supersite centered on N332 in the V3 base of the HIV-1 envelope (Env) is a target for broadly neutralizing antibodies (bnAbs) such as PGT121 and PGT128. In this study, we examined the basis of resistance of HIV-1 clade C Envs obtained from broadly cross neutralizing (BCN) plasma of an Indian donor with N332...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-016-0297-2
更新日期:2016-08-30 00:00:00
abstract::Efforts to assess the prevalence of xenotropic murine leukemia virus-related virus (XMRV) in patients with prostate cancer and chronic fatigue syndrome have relied heavily on PCR-based testing of clinical samples and have yielded widely divergent findings. This week in Retrovirology, reports from four independent rese...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-7-112
更新日期:2010-12-20 00:00:00
abstract:BACKGROUND:We previously demonstrated that primary Th1Th17 cells are highly permissive to HIV-1, whereas Th1 cells are relatively resistant. Molecular mechanisms underlying these differences remain unknown. RESULTS:Exposure to replication competent and single-round VSV-G pseudotyped HIV strains provide evidence that s...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-10-160
更新日期:2013-12-21 00:00:00
abstract:BACKGROUND:LILRA3 is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells. LILRA3 has a deletion genotype which is associated with multiple immune disorders. In this study, we wanted to analyze the regulation of LILRA3 and its significance in the context of HIV infection. R...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-016-0248-y
更新日期:2016-03-12 00:00:00
abstract:BACKGROUND:Existing highly active antiretroviral therapy (HAART) effectively controls viral replication in human immunodeficiency virus type 1 (HIV-1) infected individuals but cannot completely eradicate the infection, at least in part due to the persistence of latently infected cells. One strategy that is being active...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-10-120
更新日期:2013-10-24 00:00:00
abstract:BACKGROUND:Accumulating data suggest that immune effector functions mediated through the Fc portion of HIV-1-specific immunoglobulin G (IgG) are a key component of HIV-1 protective immunity, affecting both disease progression and HIV-1 acquisition. Through studying Fc gamma receptor (FcγR) variants known to alter IgG F...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-016-0272-y
更新日期:2016-06-10 00:00:00
abstract::This editorial represents a plea to retrovirologists to attend the XVI International Conference on AIDS that will take place in Toronto, Canada between August 13-18, 2006. In short, it is vital that politicians and opinion leaders understand that basic scientists are no less committed to the worldwide battle against H...
journal_title:Retrovirology
pub_type: 社论
doi:10.1186/1742-4690-3-9
更新日期:2006-02-03 00:00:00
abstract::HIV viruses encode a set of accessory proteins, which are important determinants of virulence due to their ability to manipulate the host cell physiology for the benefit of the virus. Although these viral proteins are dispensable for viral growth in many in vitro cell culture systems, they influence the efficiency of ...
journal_title:Retrovirology
pub_type: 杂志文章,评审
doi:10.1186/1742-4690-7-35
更新日期:2010-04-09 00:00:00
abstract:BACKGROUND:The human T-cell leukemia virus type 1 (HTLV-1) Tax protein indirectly influences transcriptional activation, signal transduction, cell cycle control, and apoptosis. The function of Tax primarily relies on protein-protein interactions. We have previously shown that Tax upregulates the cell cycle checkpoint p...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-1-6
更新日期:2004-04-13 00:00:00
abstract::We have obtained the 1.7 A crystal structure of FIV protease (PR) in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild type FIV an...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-4-1
更新日期:2007-01-09 00:00:00
abstract:BACKGROUND:We previously showed that the gM of HSV-1 could restrict the release of infectious HIV-1 from cells. In this study, we analyzed if the four HSV-1 glycoproteins (gD, gB, and gH/gL), which are the minimum glycoproteins required for HSV-1 entry, restricted the release of infectious HIV-1. RESULTS:Of these four...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-019-0470-5
更新日期:2019-04-02 00:00:00
abstract::For many years, scientists and suppliers have refered to AMV-RT as the reverse transcriptase produced by the Avian Myelobalstosis Virus. This manuscript briefly reviews the molecular basis for biological dependence of AMV for the envelope and RT proteins that are produced by its natural helper the Myeloblastosis Assoc...
journal_title:Retrovirology
pub_type: 杂志文章,评审
doi:10.1186/1742-4690-5-49
更新日期:2008-06-16 00:00:00