Abstract:
:Previous studies have demonstrated that nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) act as chemical enhancers of human immunodeficiency virus type 1 (HIV-1) RT dimerization. In the current study, we sought to define the role of key residues (101, 103, 108, 181, 188, 190, 225 and 318) in the NNRTI-binding pocket on HIV-1 RT heterodimer stability. Thirteen mutant RTs were constructed and evaluated for p66/p51 RT heterodimer formation using the well-established yeast two-hybrid assay. We found that the mutations K101A, P225H, Y318F and Y318W decreased RT heterodimer stability whereas K103N, V108I, V108W, Y181C, Y188L, G190A, G190E, G190W and P225W increased RT heterodimer stability. While these results demonstrate that residues that comprise the NNRTI-binding pocket contribute to the stability of p66/p51 HIV-1 RT, they did not suggest any obvious correlation between RT dimer stability and the extent of NNRTI resistance. Remarkably, mutations at residue G190 (A, E, W) in the p66 RT subunit were found to dramatically increase heterodimer stability. Notably, the G190W mutation increased RT dimer stability almost to the same extent as did 5 microM efavirenz. In light of these findings, we characterized the in vitro activity of recombinant RT expressing mutations at G190 in the p66 subunit only and compared them with a wild-type enzyme complexed with efavirenz. We found that while mutations at G190 had a significant effect on both the DNA polymerase and ribonuclease H activity of the enzyme, their phenotypic effects did not mirror those induced by efavirenz-binding to RT.
journal_name
Curr HIV Resjournal_title
Current HIV researchauthors
Figueiredo A,Zelina S,Sluis-Cremer N,Tachedjian Gdoi
10.2174/157016208783885065subject
Has Abstractpub_date
2008-03-01 00:00:00pages
130-7issue
2eissn
1570-162Xissn
1873-4251journal_volume
6pub_type
杂志文章abstract::Antiretroviral therapy (ART), for those who have access, has revolutionised the morbidity and mortality consequences of HIV infection. By the end of 2010, 6.6 million people living with HIV in low- and middle-income countries were receiving ART, a dramatic 20-fold increase since 2001, saving millions of lives. In addi...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016211798038579
更新日期:2011-09-01 00:00:00
abstract::Although hepatitis B serology screening has been recommended for HIV care, it has not been routinely performed. We aimed to assess compliance and timing of hepatitis B serology screening among HIV-infected patients in a resource-limited setting. A cross-sectional study was conducted in Thailand. Compliance, timing of ...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016211794582669
更新日期:2011-01-01 00:00:00
abstract::A major hurdle in the development of a global HIV-1 vaccine is viral diversity. For close to three decades, HIV vaccine development has focused on either the induction of T cell immune responses or antibody responses, and only rarely on both components. After the failure of the STEP trial, the scientific community con...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016210794088290
更新日期:2010-12-01 00:00:00
abstract::Objective was to assess dietary intake and physical activity in a Canadian population sample of male patients with HIV and metabolic abnormalities and to compare the data to Canadian recommendations. Sixty-five HIV-infected men with at least one feature associated with the metabolic syndrome (insulin resistance, dysli...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016208783571973
更新日期:2008-01-01 00:00:00
abstract::Human immunodeficiency virus has evolved several redundant mechanisms to remove its receptor, the CD4 molecule, from the cell surface. Indeed, HIV-1 encodes three proteins, Nef, Vpu and Env, that have a profound effect on CD4 trafficking and catabolism. Given this functional convergence, it is believed that cell surfa...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162043485086
更新日期:2004-01-01 00:00:00
abstract::Antiretroviral drug therapy has significantly improved the prognosis and life expectancy of people living with HIV over the years. But this progress comes with an important caveat that antiretroviral regimens generally require adherence to life-long, daily dosing, to keep viral multiplication under check. Non-adherenc...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666200824104140
更新日期:2020-08-23 00:00:00
abstract:BACKGROUND:HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade's polymorphisms in its functionally critical regions protease and reverse transcriptase. OBJECTIVE:To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its pare...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666200415140652
更新日期:2020-01-01 00:00:00
abstract::The development of pre-exposure prophylactics or microbicide products for the reduction or elimination of the sexual transmission of HIV has numerous challenges or barriers to success. Historically traditional dosage forms such as gels have been developed in the field but more recently controlled release dosage forms ...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016212799304599
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:The change in the prevalence of hypogonadism with age in men with human immunodeficiency virus (HIV) infection is subject to debate. OBJECTIVE:To address this issue, we diagnosed hypogonadism based on serum levels of free testosterone (fTST) rather than total testosterone which is thought to be an inaccurat...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666200720000344
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVE:HIV lipodystrophy is characterised by abnormal adipose tissue distribution and metabolism, as a result of altered adipocyte function and gene expression. The protease inhibitor ritonavir is associated with the development of lipodystrophy. Quantifying changes in adipogenic gene expression in the presence of r...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x13666150806110238
更新日期:2016-01-01 00:00:00
abstract::An estimated 800,000 children acquired HIV-infection in 2002, most as a result of mother-to-child transmission (MTCT), and vertically-acquired HIV infection continues to be of major public health importance. Prevention of MTCT is possible with a combination of interventions including antiretroviral therapy (ART) (usua...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162033485140
更新日期:2003-10-01 00:00:00
abstract::Mutation of the human immunodeficiency virus by host cells inhibits viral dissemination by creating non-functional variants. However, viral mutation does not always eliminate the ability of the virus to disseminate and, in fact, is thought to promote persistence by generating functional mutants that evade immunity or ...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016208783571919
更新日期:2008-01-01 00:00:00
abstract::Immunization is an important measure to protect HIV-infected children and adults against certain vaccine preventable diseases. However, the antibody response, which is associated with the level of CD4+ T cell count, is frequently impaired in this group of patients. Certain vaccines enhance virus replication and transi...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162043351084
更新日期:2004-10-01 00:00:00
abstract::AIDS has claimed the lives of 25 million people worldwide, an additional 40 million people are HIV-infected and new cases are being diagnosed every year. Despite the fact that HAART has moved AIDS from the category of terminal diseases to that of treatable chronic illnesses, its long-term therapeutic success may be co...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016207781023965
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:Genetic variations in Human leukocyte antigen C (HLA-C), Zinc ribbon domain containing 1 (ZNRD1) and its antisense RNA (ZNRD1-AS1) genes are known to influence the HIV-1 replication and disease progression. OBJECTIVE AND METHOD:We evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X15666170511141741
更新日期:2017-01-01 00:00:00
abstract::VGV-1, a clinical-grade formulation of bovine thymus nuclear protein (TNP) has been demonstrated to possess anti-viral activity in HIV-1 patients in five clinical trials, one of which was placebo controlled double-blinded. However, to date molecular mechanisms remain to be identified. Using surface plasmon resonance w...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016208785132545
更新日期:2008-06-01 00:00:00
abstract::A major focus of HIV-1 vaccine development has been directed towards a limited number of broadly conserved epitopes in the Envelope (Env) proteins that are sensitive neutralization targets in many primary isolates. However, evidence suggests that these epitopes are poorly immunogenic; similar antibodies are rarely pro...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016207782418470
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:The primary objective of this study was to estimate etravirine activity in a cohort of patients infected with non-B subtype HIV-1 and failing nevirapine-based therapy. MATERIALS AND METHODS:Genotypic resistance testing was performed if viral load was >OR= 1,000 copies/ml after receiving at least six months o...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016210791111098
更新日期:2010-04-01 00:00:00
abstract:BACKGROUND:The emergence of drug-resistant viral strains has created the need for the development of novel anti-HIV agents with a diverse structure that targets key enzymes in the HIV lifecycle. OBJECTIVE:Considering the pharmacophore of integrase inhibitors, one of the validated targets for anti-HIV therapy, we desig...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X17666191210105809
更新日期:2020-01-01 00:00:00
abstract::Enteroaggregative Escherichia coli (EAEC) have been isolated from both HIV-positive and non-HIV diarrheal samples. In this study a collection of 18 isolates from these two groups were compared for biofilm formation and antibiotic resistance and for the presence of 14 virulence-related genes. All the HIV-positive and o...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x12666140207161000
更新日期:2013-12-01 00:00:00
abstract::While significant progress has been made since 2003 when a comprehensive treatment, prevention and control program was implemented to combat the HIV/AIDS epidemic in China, new challenges are emerging. There have been limited direct case reports on profiles of HIV/AIDS patients under care at unique clinical settings i...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016210793499169
更新日期:2010-10-01 00:00:00
abstract::Over the past 10 years substantial progress has been made in the implementation of prevention of mother-to-child transmission of HIV (PMTCT) interventions in Sub-Saharan Africa (SSA). In spite of this, new pediatric infections remain unacceptably high, contributing the majority (>90%) of the estimated 390,000 infectio...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162x11311020007
更新日期:2013-03-01 00:00:00
abstract::The aim of the study was to report the epidemiological profile of HIV-1 positive patients from, Istanbul, Turkey, which has one of the lowest HIV-1/AIDS prevalences in Europe. The patients were followed by ACTHIV-IST group which was established by the Infectious Diseases Departments of five teaching hospitals (three u...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x12666140411111803
更新日期:2014-01-01 00:00:00
abstract::Jembrana disease virus (JDV) is the most recently discovered member of the lentivirus family and causes an acute clinical disease in Bali cattle with a fatality rate of approximately 15%. It is genetically related to bovine immunodeficiency virus (BIV) to the extent that infections cannot yet be differentially diagnos...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016210790416370
更新日期:2010-01-01 00:00:00
abstract::Revised Centers for Disease Control and Prevention recommendations on HIV testing now promote testing of most risk groups. However, positive results for low-risk individuals are more likely to be false positives than for high-risk individuals, making clear communication of test results even more imperative. In a study...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x13666150511125629
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus (HIV) infection is a global health burden which ultimately results in acquired immune deficiency syndrome (AIDS). There are multiple host factors which are capable of limiting HIV-1 replication. One of the most important host factors which inhibit HIV-1 DNA synthesis is the apoli...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X16666181018155827
更新日期:2018-01-01 00:00:00
abstract::After the infusion of HIV-1 virus into a host cell, RNA is reverse transcribed to dsDNA, which persists intracellular to the infected cell in a variety of forms. Numerous in-house assays have been developed for the quantification of the different cellular HIV-1 DNA forms; these implement conventional or real-time PCR ...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016209788348001
更新日期:2009-05-01 00:00:00
abstract::The cellular protein "Bone marrow stromal antigen 2" (BST2 also called Tetherin, CD317, HM1.24) was identified as a major mediator of the innate immune defense against the dissemination of enveloped viruses. BST2 was shown to physically trap the de novo formed viral particles at the surface of infected cells, thereby ...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016212800792414
更新日期:2012-06-01 00:00:00
abstract::HIV-associated neurocognitive disorders (HAND) remain prevalent despite effective combined anti-retroviral therapy (cART). Cognitive function has been shown to inversely correlate with decreased synaptic and dendritic density. In this study, macaques inoculated with SIV were examined over a 3-month course of infection...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x1131100049
更新日期:2013-06-01 00:00:00
abstract::Neisseria gonorrhoeae (GC), a major cause of pelvic inflammatory disease, can facilitate HIV transmission. In response to GC infection, genital epithelial cells can produce cytokines, chemokines and defensins to modulate HIV infection and infectivity. GC can also induce the production of cytokines and chemokines in mo...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016212800618138
更新日期:2012-04-01 00:00:00