Abstract:
:Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells with replication competent HIV proviruses form a reservoir that persists despite cART and such reservoirs are at the center of efforts to eradicate or control infection without cART. The mechanisms of persistence of these chronically infected long-lived cells is uncertain, but recent research has demonstrated that the presence of the HIV provirus has enduring effects on infected cells. Cells with integrated proviruses may persist for many years, undergo clonal expansion, and produce replication competent HIV. Even proviruses with defective genomes can produce HIV RNA and may contribute to ongoing HIV pathogenesis. New analyses of HIV infected cells suggest that over time on cART, there is a shift in the composition of the population of HIV infected cells, with the infected cells that persist over prolonged periods having proviruses integrated in genes associated with regulation of cell growth. In several cases, strong evidence indicates the presence of the provirus in specific genes may determine persistence, proliferation, or both. These data have raised the intriguing possibility that after cART is introduced, a selection process enriches for cells with proviruses integrated in genes associated with cell growth regulation. The dynamic nature of populations of cells infected with HIV during cART is not well understood, but is likely to have a profound influence on the composition of the HIV reservoir with critical consequences for HIV eradication and control strategies. As such, integration studies will shed light on understanding viral persistence and inform eradication and control strategies. Here we review the process of HIV integration, the role that integration plays in persistence, clonal expansion of the HIV reservoir, and highlight current challenges and outstanding questions for future research.
journal_name
Retrovirologyjournal_title
Retrovirologyauthors
Anderson EM,Maldarelli Fdoi
10.1186/s12977-018-0448-8subject
Has Abstractpub_date
2018-10-23 00:00:00pages
71issue
1issn
1742-4690pii
10.1186/s12977-018-0448-8journal_volume
15pub_type
杂志文章,评审相关文献
Retrovirology文献大全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:It has been accepted that HIV buds from the cell surface in T lymphocytes, whereas in macrophages it buds into intracellular endosomes. Recent studies, on the other hand, suggest that HIV preferentially buds from the cell surface even in monocytic cells. However, most studies are based on observations in acu...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-6-63
更新日期:2009-07-13 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:The N-heptad repeat region of the HIV-1 Transmembrane Envelope protein is a trimerization domain that forms part of a "six helix bundle" crucial to Envelope-mediated membrane fusion. N-heptad repeat peptides have been used as extracellular reagents to inhibit virus fusion. RESULTS:When expressed intracellul...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-2-51
更新日期:2005-08-10 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: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...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-9-68
更新日期:2012-08-13 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:HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF interaction during...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-017-0373-2
更新日期:2017-11-09 00:00:00
abstract::HTLV-1 was the first described human retrovirus and was soon found to be associated with severe clinical diseases, including a devastating lymphoma/leukemia and other inflammatory diseases. Although HTLV-2 is not usually pathogenic, it is widely distributed among native Indian populations in Brazil, particularly in th...
journal_title:Retrovirology
pub_type: 杂志文章,评审
doi:10.1186/s12977-020-0512-z
更新日期:2020-02-14 00:00:00
abstract:BACKGROUND:Reverse transcription (RT) of HIV and SIV is initiated by the binding of the acceptor stem of tRNALys3 to the primer binding site (PBS) of the viral RNA genome. Previous studies have suggested that this tRNALys3 is not the only molecule capable of priming reverse transcription, and that at least one other ly...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-019-0473-2
更新日期:2019-04-04 00:00:00
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 defi...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-016-0284-7
更新日期:2016-07-26 00:00:00
abstract:BACKGROUND:Regulatory T cells (Tregs) have been shown to limit anti-viral immunity during chronic retroviral infection and to restrict vaccine-induced T cell responses. The objective of the study was to assess whether a combinational therapy of nanoparticle-based therapeutic vaccination and concomitant transient ablati...
journal_title:Retrovirology
pub_type: 杂志文章,评审
doi:10.1186/s12977-016-0258-9
更新日期:2016-04-14 00:00:00
abstract:BACKGROUND:The reliable diagnosis of human T-cell leukemia virus type 1 (HTLV-1) infection is important, particularly as it can be vertically transmitted by breast feeding mothers to their infants. However, current diagnosis in Japan requires a confirmatory western blot (WB) test after screening/primary testing for HTL...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-020-00534-0
更新日期:2020-08-24 00:00:00
abstract::In order to characterize the antiviral activity of human TRIM5alpha in more detail human derived indicator cell lines over expressing wild type human TRIM5alpha were generated and challenged with HIV-1 and HIV-2 viruses pseudotyped with HIV envelope proteins in comparison to VSV-G pseudotyped particles. HIV envelope p...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-3-79
更新日期:2006-11-06 00:00:00
abstract::Recent findings suggest that mammalian cells can use small non-coding RNAs (ncRNA) to regulate physiological viral infections. Here, we comment on several lines of evidence that support this concept. We discuss how viruses may in turn protect, suppress, evade, modulate, or adapt to the host cell's ncRNA regulatory sch...
journal_title:Retrovirology
pub_type: 社论,评审
doi:10.1186/1742-4690-4-74
更新日期:2007-10-15 00:00:00
abstract:BACKGROUND:HIV-1 typically develops resistance to any single antiretroviral agent. Combined anti-retroviral therapy to reduce drug-resistance development is necessary to control HIV-1 infection. Here, to assess the utility of a combination of antibody and fusion inhibitor treatments, we investigated the potency of mono...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-016-0304-7
更新日期:2016-09-27 00:00:00
abstract:BACKGROUND:All human immunodeficiency virus (HIV-1) uses a host tRNALys,3 as the primer for reverse transcription. The tRNALys,3 is bound to a region on the HIV-1 genome, the primer-binding site (PBS), that is complementary to the 18 terminal nucleotides of tRNALys,3. How HIV-1 selects the tRNA from the intracellular m...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-2-21
更新日期:2005-03-24 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: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::The human immunodeficiency virus type 1 (HIV-1) Vif plays a crucial role in the viral life cycle by antagonizing a host restriction factor APOBEC3G (A3G). Vif interacts with A3G and induces its polyubiquitination and subsequent degradation via the formation of active ubiquitin ligase (E3) complex with Cullin5-ElonginB...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-6-1
更新日期:2009-01-07 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:The HIV-1 Rev regulatory protein binds as an oligomeric complex to viral RNA mediating nuclear export of incompletely spliced and non-spliced viral mRNAs encoding the viral structural proteins. However, the biological significance of the obligatory complex formation of Rev upon the viral RNA is unclear. RES...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/1742-4690-2-39
更新日期:2005-06-10 00:00:00
abstract:BACKGROUND:Interferon induced transmembrane proteins 1, 2 and 3 (IFITMs) belong to a family of highly related antiviral factors that have been shown to interfere with a large spectrum of viruses including Filoviruses, Coronaviruses, Influenza virus, Dengue virus and HIV-1. In all these cases, the reported mechanism of ...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-014-0103-y
更新日期:2014-11-25 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:BACKGROUND:Integration of retroviral DNA into a germ cell can result in a provirus that is transmitted vertically to the host's offspring. In humans, such endogenous retroviruses (HERVs) comprise >8% of the genome. The HERV-K(HML-2) proviruses consist of ~90 elements related to mouse mammary tumor virus, which causes b...
journal_title:Retrovirology
pub_type: 杂志文章
doi:10.1186/s12977-014-0062-3
更新日期:2014-08-12 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: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: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::MicroRNAs are a recently discovered class of small noncoding functional RNAs. These molecules mediate post-transcriptional regulation of gene expression in a sequence specific manner. MicroRNAs are now known to be key players in a variety of biological processes and have been shown to be deregulated in a number of can...
journal_title:Retrovirology
pub_type: 社论,评审
doi:10.1186/1742-4690-4-82
更新日期:2007-11-24 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