Abstract:
BACKGROUND:Eradication of HIV cannot be achieved with combination antiretroviral therapy (cART) because of the persistence of long-lived latently infected resting memory CD4(+) T cells. We previously reported that HIV latency could be established in resting CD4(+) T cells in the presence of the chemokine CCL19. To define how CCL19 facilitated the establishment of latent HIV infection, the role of chemokine receptor signalling was explored. RESULTS:In resting CD4(+) T cells, CCL19 induced phosphorylation of RAC-alpha serine/threonine-protein kinase (Akt), nuclear factor kappa B (NF-κB), extracellular-signal-regulated kinase (ERK) and p38. Inhibition of the phosphoinositol-3-kinase (PI3K) and Ras/Raf/Mitogen-activated protein kinase/ERK kinase (MEK)/ERK signalling pathways inhibited HIV integration, without significant reduction in HIV nuclear entry (measured by Alu-LTR and 2-LTR circle qPCR respectively). Inhibiting activation of MEK1/ERK1/2, c-Jun N-terminal kinase (JNK), activating protein-1 (AP-1) and NF-κB, but not p38, also inhibited HIV integration. We also show that HIV integrases interact with Pin1 in CCL19-treated CD4(+) T cells and inhibition of JNK markedly reduced this interaction, suggesting that CCL19 treatment provided sufficient signals to protect HIV integrase from degradation via the proteasome pathway. Infection of CCL19-treated resting CD4(+) T cells with mutant strains of HIV, lacking NF-κB binding sites in the HIV long terminal repeat (LTR) compared to infection with wild type virus, led to a significant reduction in integration by up to 40-fold (range 1-115.4, p = 0.03). This was in contrast to only a modest reduction of 5-fold (range 1.7-11, p > 0.05) in fully activated CD4(+) T cells infected with the same mutants. Finally, we demonstrated significant differences in integration sites following HIV infection of unactivated, CCL19-treated, and fully activated CD4(+) T cells. CONCLUSIONS:HIV integration in CCL19-treated resting CD4(+) T cells depends on NF-κB signalling and increases the stability of HIV integrase, which allow subsequent integration and establishment of latency. These findings have implications for strategies needed to prevent the establishment, and potentially reverse, latent infection.
journal_name
Retrovirologyjournal_title
Retrovirologyauthors
Saleh S,Lu HK,Evans V,Harisson D,Zhou J,Jaworowski A,Sallmann G,Cheong KY,Mota TM,Tennakoon S,Angelovich TA,Anderson J,Harman A,Cunningham A,Gray L,Churchill M,Mak J,Drummer H,Vatakis DN,Lewin SR,Cameron PUdoi
10.1186/s12977-016-0284-7subject
Has Abstractpub_date
2016-07-26 00:00:00pages
49issue
1issn
1742-4690pii
10.1186/s12977-016-0284-7journal_volume
13pub_type
杂志文章相关文献
Retrovirology文献大全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:Recognition of microbial products through Toll-like receptors (TLRs) initiates inflammatory responses orchestrated by innate immune cells such as dendritic cells (DCs). As these cells are patrolling mucosal surfaces, a portal of entry for various pathogens including human immunodeficiency virus type-1 (HIV-1...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-6-42
更新日期:2009-05-06 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:In chickens, as in most birds, female gonad morphogenesis is asymmetrical. Gonads appear first rather similarly, but only the left one undergoes full differentiation and gives rise to a functional ovary. The right gonad, in which the cortex does not develop, remains restricted to the medulla and finally regr...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-6-59
更新日期:2009-06-17 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:OBJECTIVES:It has been shown that socioeconomic status (SES) is associated with adherence to treatment of patients with several chronic diseases. However, there is a controversy regarding the impact of SES on adherence among patients with the human immunodeficiency virus (HIV) infection or acquired immunodeficiency syn...
journal_title:Retrovirology
pub_type: 社论,评审
doi:10.1186/1742-4690-5-13
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoti...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-10-135
更新日期:2013-11-14 00:00:00
abstract:BACKGROUND:While viruses have long been shown to capitalize on their limited genomic size by utilizing both strands of DNA or complementary DNA/RNA intermediates to code for viral proteins, it has been assumed that human retroviruses have all their major proteins translated only from the plus or sense strand of RNA, de...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-3-80
更新日期:2006-11-08 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::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::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
abstract:BACKGROUND:Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that methylates arginine residues on histones and transcription factors. In addition, PRMT6 inhibits HIV-1 replication in cell culture by directly methylating and interfering with the functions of several HIV-1 proteins, i.e. Tat, Rev and nucle...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-10-73
更新日期:2013-07-17 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:Recombination is a common feature of retroviral biology and one of the most important factors responsible for generating viral diversity at both the intra-host and the population levels. However, relatively little is known about rates and molecular processes of recombination for retroviruses other than HIV, ...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-014-0080-1
更新日期:2014-09-17 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::A pol-fragment of simian immunodeficiency virus (SIV) that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus) was detected in two mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely to be hybrids. Thei...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-1-36
更新日期:2004-11-01 00:00:00
abstract::Sidaction's appeal regarding the sentencing of medical personnels in the Libyan-HIV infection cases. ...
journal_title:Retrovirology
pub_type: 社论
doi:10.1186/1742-4690-3-98
更新日期:2006-12-27 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::Attenuation of p53 activity appears to be a major step in Human T-lymphotropic virus type 1 (HTLV-1) Tax transformation. However, p53 genomic mutations are late and rather infrequent events in HTLV-1 induced Adult T cell leukemia (ATL). The paper by Zane et al. shows that a mediator of p53 activity, Wild-type p53-indu...
journal_title:Retrovirology
pub_type: 评论,杂志文章
doi:10.1186/1742-4690-9-115
更新日期:2012-12-21 00:00:00
abstract:BACKGROUND:The continued persistence of HIV-1 as a public health concern due to the lack of a cure calls for the development of new tools for studying replication of the virus. Here, we used NanoLuc, a small and extremely bright luciferase protein, to develop an HIV-1 bioluminescent reporter virus that simplifies funct...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-020-00521-5
更新日期:2020-05-19 00:00:00
abstract::Integration of the reverse transcribed viral genome into host chromatin is the hallmark of retroviral replication. Yet, during natural HIV infection, various unintegrated viral DNA forms exist in abundance. Though linear viral cDNA is the precursor to an integrated provirus, increasing evidence suggests that transcrip...
journal_title:Retrovirology
pub_type: 杂志文章,评审
doi:10.1186/1742-4690-8-52
更新日期:2011-07-01 00:00:00
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 b...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-3-97
更新日期:2006-12-21 00:00:00
abstract:BACKGROUND:A nef gene is present in all primate lentiviral genomes and is important for high viral loads and progression to AIDS in human or experimental macaque hosts of HIV or SIV, respectively. In these hosts, infection of the thymus results in a decreased output of naive T cells that may contribute to the developme...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-10-137
更新日期:2013-11-15 00:00:00
abstract:BACKGROUND:We reported previously that while prolonged tenofovir monotherapy of macaques infected with virulent simian immunodeficiency virus (SIV) resulted invariably in the emergence of viral mutants with reduced in vitro drug susceptibility and a K65R mutation in reverse transcriptase, some animals controlled virus ...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-9-57
更新日期:2012-07-17 00:00:00
abstract:BACKGROUND:Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracell...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-9-17
更新日期:2012-02-20 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: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:Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and associ...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-8-23
更新日期:2011-03-29 00:00:00
abstract:BACKGROUND:HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference dur...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-016-0266-9
更新日期:2016-05-03 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