Abstract:
BACKGROUND:Thymidine analogue resistance mutations (TAMs) selected under treatment with nucleoside analogues generate two distinct genotypic profiles in the HIV-1 reverse transcriptase (RT): (i) TAM1: M41L, L210W and T215Y, and (ii) TAM2: D67N, K70R and K219E/Q, and sometimes T215F. Secondary mutations, including thumb subdomain polymorphisms (e.g. R284K) have been identified in association with TAMs. We have identified mutational clusters associated with virological failure during salvage therapy with tenofovir/emtricitabine-based regimens. In this context, we have studied the role of R284K as a secondary mutation associated with mutations of the TAM1 complex. RESULTS:The cross-sectional study carried out with > 200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P < 10-10) and TAMs (P < 10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy. Clusters of mutations were identified, and among them, the TAM1 complex showed the highest correlation coefficients. Covariation of TAM1 mutations and V118I, V179I, M184V and R284K was observed. Virological studies showed that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of zidovudine or tenofovir. Studies with recombinant HIV-1 RTs showed that when associated with TAM1 mutations, R284K had a minimal impact on zidovudine or tenofovir inhibition, and in their ability to excise the inhibitors from blocked DNA primers. However, the mutant RT M41L/L210W/T215Y/R284K showed an increased catalytic rate for nucleotide incorporation and a higher RNase H activity in comparison with WT and mutant M41L/L210W/T215Y RTs. These effects were consistent with its enhanced chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes, and can explain the higher fitness of HIV-1 having TAM1/R284K mutations. CONCLUSIONS:Our study shows the association of R284K and TAM1 mutations in individuals failing therapy with tenofovir/emtricitabine, and unveils a novel mechanism by which secondary mutations are selected in the context of drug-resistance mutations.
journal_name
Retrovirologyjournal_title
Retrovirologyauthors
Betancor G,Garriga C,Puertas MC,Nevot M,Anta L,Blanco JL,Pérez-Elías MJ,de Mendoza C,Martínez MA,Martinez-Picado J,Menéndez-Arias L,Resistance Platform of the Spanish AIDS Research Network (ResRIS).,Iribarren JA,Caballero E,Rdoi
10.1186/1742-4690-9-68subject
Has Abstractpub_date
2012-08-13 00:00:00pages
68issn
1742-4690pii
1742-4690-9-68journal_volume
9pub_type
杂志文章相关文献
Retrovirology文献大全abstract:BACKGROUND:Platelets are associated with HIV in the blood of infected individuals and might modulate viral dissemination, particularly if the virus is directly transmitted into the bloodstream. The C-type lectin DC-SIGN and the novel HIV attachment factor CLEC-2 are expressed by platelets and facilitate HIV transmissio...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-7-47
更新日期:2010-05-19 00:00:00
abstract:BACKGROUND:HIV infection results in inhibited cholesterol efflux by apolipoprotein A-I (apoA-I) in macrophages, and this impairment involves Nef mediated down-regulation and redistribution of ATP-binding cassette transporter A1 (ABCA-1). We investigated the effect of caveolin-1 (Cav-1) on the cholesterol efflux by apoA...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-9-85
更新日期:2012-10-15 00:00:00
abstract:BACKGROUND:The Tax proteins encoded by human T lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) are transcriptional activators of both the viral long terminal repeat (LTR) and cellular promoters via the CREB and NFkB pathways. In contrast to HTLV-1, HTLV-2 has been classified into four distinct genetic subtypes A...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-3-20
更新日期:2006-03-21 00:00:00
abstract:BACKGROUND:HIV-1 Gag proteins are essential for virion assembly and viral replication in newly infected cells. Gag proteins are also strong determinants of viral infectivity; immune escape mutations in the Gag capsid (CA) protein can markedly reduce viral fitness, and interactions of CA with host proteins such as cyclo...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-6-21
更新日期:2009-03-02 00:00:00
abstract::Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all simian species. Subsequent molecular epidemiology studies demonstrated that, apart from HTLV-1 subtype A, all human subtypes have a simian homolog. As...
journal_title:Retrovirology
pub_type: 杂志文章,评审
doi:10.1186/s12977-019-0503-0
更新日期:2019-12-16 00:00:00
abstract:BACKGROUND:Despite intensive investigation the mechanism by which HIV-1 reaches the host cell nucleus is unknown. TNPO3, a karyopherin mediating nuclear entry of SR-proteins, was shown to be required for HIV-1 infectivity. Some investigators have reported that TNPO3 promotes HIV-1 nuclear import, as would be expected f...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-10-20
更新日期:2013-02-15 00:00:00
abstract:BACKGROUND:In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer reco...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-7-38
更新日期:2010-04-26 00:00:00
abstract:BACKGROUND:HIV infection and antiretroviral treatment are associated with changes in lipid levels, insulin resistance and risk of cardiovascular disease (CVD). We investigated these changes in the first 96 weeks of treatment with low-dose stavudine or tenofovir regimens. METHODS:This is a secondary analysis of a doubl...
journal_title:Retrovirology
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12977-018-0460-z
更新日期:2018-12-14 00:00:00
abstract::The King's College London (KCL) Infectious Diseases BioBank opened in 2007 and collects peripheral venous blood (PVB) from individuals infected with pathogens including human immunodeficiency virus (HIV). PVBs are fractionated into plasmas, lymphocytes and DNA and are then frozen. All donations are from subjects who h...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-6-98
更新日期:2009-11-03 00:00:00
abstract:BACKGROUND:Toll-like receptors (TLRs) are crucial for recognition of pathogen-associated molecular patterns by cells of the innate immune system. TLRs are present and functional in CD4⁺ T cells. Memory CD4⁺ T cells, predominantly central memory cells (TCM), constitute the main reservoir of latent HIV-1. However, how TL...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-10-119
更新日期:2013-10-24 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:Formation of a mature core is a crucial event for infectivity of retroviruses such as Mason-Pfizer monkey virus (M-PMV). The process is triggered by proteolytic cleavage of the polyprotein precursor Gag, which releases matrix, capsid (CA), and nucleocapsid proteins. Once released, CA assembles to form a matu...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-014-0094-8
更新日期:2014-10-30 00:00:00
abstract:BACKGROUND:Long term infection with HIV-1, even in the context of therapy, leads to chronic health problems including an array of neurocognitive dysfunctions. The viral Tat protein has previously been implicated in neuropathogenesis through its effect on astrocytes. Tat has also been shown to inhibit the biogenesis of ...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-016-0256-y
更新日期:2016-04-08 00:00:00
abstract:BACKGROUND:The APOBEC3 (A3) family of DNA cytosine deaminases provides an innate barrier to infection by retroviruses including HIV-1. A total of five enzymes, A3C, A3D, A3F, A3G and A3H, are degraded by the viral accessory protein Vif and expressed at high levels in CD4+ T cells, the primary reservoir for HIV-1 replic...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-018-0459-5
更新日期:2018-12-17 00:00:00
abstract:BACKGROUND:Unlike CD4+ T cells, HIV-1 infected macrophages exhibit extended life span even upon stress, consistent with their in vivo role as long-lived HIV-1 reservoirs. RESULTS:Here, we demonstrate that PI3K/Akt inhibitors, including clinically available Miltefosine, dramatically reduced HIV-1 production from long-l...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-5-11
更新日期:2008-01-31 00:00:00
abstract:BACKGROUND:The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycop...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-9-48
更新日期:2012-05-31 00:00:00
abstract:BACKGROUND:HIV-1 infects a wide range of CD4+ T cells with different phenotypic properties and differing expression levels of entry coreceptors. We sought to determine the viral tropism of subtype C (C-HIV) Envelope (Env) clones for different CD4+ T cell subsets and whether tropism changes during acute to chronic disea...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-020-00532-2
更新日期:2020-08-06 00:00:00
abstract::Members of the APOBEC family of cellular cytidine deaminases represent a recently identified group of proteins that provide immunity to infection by retroviruses and protect the cell from endogenous mobile retroelements. Yet, HIV-1 is largely immune to the intrinsic antiviral effects of APOBEC proteins because it enco...
journal_title:Retrovirology
pub_type: 杂志文章,评审
doi:10.1186/1742-4690-5-51
更新日期:2008-06-24 00:00:00
abstract::How best to evaluate scientists within a peer group is a difficult task. This editorial discusses the use of the H-index and total citations. It also raises the consideration of a mentoring-index and the value of understanding the frequency that a published paper is accessed by readers. ...
journal_title:Retrovirology
pub_type: 社论
doi:10.1186/1742-4690-5-106
更新日期:2008-11-25 00:00:00
abstract:BACKGROUND:Adult T-cell leukemia lymphoma (ATLL) is a chemotherapy-resistant malignancy with a median survival of less than one year that will afflict between one hundred thousand and one million individuals worldwide who are currently infected with human T-cell leukemia virus type 1. Recurrent somatic mutations in hos...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-020-00535-z
更新日期:2020-08-28 00:00:00
abstract:BACKGROUND:Reducing transmission of HIV-1 through breast milk is needed to help decrease the burden of pediatric HIV/AIDS in society. We have previously reported that alkyl sulfates (i.e., sodium dodecyl sulfate, SDS) are microbicidal against HIV-1 at low concentrations, are biodegradable, have little/no toxicity and a...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-2-28
更新日期:2005-04-29 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: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:International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patie...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-10-36
更新日期:2013-04-03 00:00:00
abstract:BACKGROUND:HIV-1 replication is critically dependent upon controlled processing of its RNA and the activities provided by its encoded regulatory factors Tat and Rev. A screen of small molecule modulators of RNA processing identified several which inhibited virus gene expression, affecting both relative abundance of spe...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-017-0330-0
更新日期:2017-01-26 00:00:00
abstract:BACKGROUND:A critical step for retroviral replication is the stable integration of the provirus into the genome of its host. The viral integrase protein is key in this essential step of the retroviral life cycle. Although the basic mechanism of integration by mammalian retroviruses has been well characterized, the fact...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-5-48
更新日期:2008-06-13 00:00:00
abstract:BACKGROUND:Endogenous retroviruses (ERVs) are genetic elements with a retroviral origin that are integrated into vertebrate genomes. In felids (Mammalia, Carnivora, Felidae), ERVs have been described mostly in the domestic cat, and only rarely in wild species. To gain insight into the origins and evolutionary dynamics ...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-015-0152-x
更新日期:2015-03-15 00:00:00
abstract::The viral transactivator of HTLV-I, Tax, has long been shown to target the earliest steps of transcription by forming quaternary complexes with sequence specific transcription factors and histone-modifying enzymes in the LTR of HTLV-I. However, a new study suggests that Tax preferentially transactivates the 21-bp repe...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-1-19
更新日期:2004-07-30 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:SAMHD1 is an HIV-1 restriction factor in non-dividing monocytes, dendritic cells (DCs), macrophages, and resting CD4+ T-cells. Acting as a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, SAMHD1 hydrolyzes dNTPs and restricts HIV-1 infection in macrophages and resting CD4+ T-cells by decreasing the i...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-9-105
更新日期:2012-12-11 00:00:00