Host mRNA decay proteins influence HIV-1 replication and viral gene expression in primary monocyte-derived macrophages.


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 (HIV-1) infection is yet to be elucidated. Macrophages are directly infected by HIV-1, mediate the dissemination of the virus and contribute to the chronic activation of the inflammatory response observed in infected individuals. Therefore, we characterized the effects of four host mRNA decay proteins, i.e., UPF1, UPF2, SMG6 and Staufen1, on viral replication in HIV-1-infected primary monocyte-derived macrophages (MDMs). RESULTS:Steady-state expression levels of these host mRNA decay proteins were significantly downregulated in HIV-1-infected MDMs. Moreover, UPF2 and SMG6 inhibited HIV-1 gene expression in macrophages to a similar level achieved by SAMHD1, by directly influencing viral genomic RNA levels. Staufen1, a host protein also involved in UPF1-dependent mRNA decay and that acts at several HIV-1 replication steps, enhanced HIV-1 gene expression in MDMs. CONCLUSIONS:These results provide new evidence for roles of host mRNA decay proteins in regulating HIV-1 replication in infected macrophages and can serve as potential targets for broad-spectrum antiviral therapeutics.






Rao S,Amorim R,Niu M,Breton Y,Tremblay MJ,Mouland AJ




Has Abstract


2019-02-07 00:00:00












  • TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads.

    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...


    pub_type: 杂志文章


    authors: Low HZ,Ahrenstorf G,Pommerenke C,Habermann N,Schughart K,Ordóñez D,Stripecke R,Wilk E,Witte T

    更新日期:2016-03-12 00:00:00

  • Identification of a tripartite interaction between the N-terminus of HIV-1 Vif and CBFβ that is critical for Vif function.

    abstract:BACKGROUND:HIV-1 Vif interacts with the cellular core-binding factor β (CBFβ) and counteracts the protective roles of certain human APOBEC3 (A3) proteins by targeting them for proteasomal degradation. Previous studies have identified some amino acids important for Vif-CBFβ interactions, and recently a co-crystal struct...


    pub_type: 杂志文章


    authors: Desimmie BA,Smith JL,Matsuo H,Hu WS,Pathak VK

    更新日期:2017-03-17 00:00:00

  • Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein.

    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...


    pub_type: 杂志文章


    authors: Nangola S,Urvoas A,Valerio-Lepiniec M,Khamaikawin W,Sakkhachornphop S,Hong SS,Boulanger P,Minard P,Tayapiwatana C

    更新日期:2012-02-20 00:00:00

  • Evolution and gene capture in ancient endogenous retroviruses - insights from the crocodilian genomes.

    abstract:BACKGROUND:Crocodilians are thought to be hosts to a diverse and divergent complement of endogenous retroviruses (ERVs) but a comprehensive investigation is yet to be performed. The recent sequencing of three crocodilian genomes provides an opportunity for a more detailed and accurate representation of the ERV diversit...


    pub_type: 杂志文章


    authors: Chong AY,Kojima KK,Jurka J,Ray DA,Smit AF,Isberg SR,Gongora J

    更新日期:2014-12-12 00:00:00

  • Longitudinal analysis of subtype C envelope tropism for memory CD4+ T cell subsets over the first 3 years of untreated HIV-1 infection.

    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...


    pub_type: 杂志文章


    authors: Gartner MJ,Gorry PR,Tumpach C,Zhou J,Dantanarayana A,Chang JJ,Angelovich TA,Ellenberg P,Laumaea AE,Nonyane M,Moore PL,Lewin SR,Churchill MJ,Flynn JK,Roche M

    更新日期:2020-08-06 00:00:00

  • Single genome analysis reveals genetic characteristics of Neuroadaptation across HIV-1 envelope.

    abstract:BACKGROUND:The widespread use of highly effective, combination antiretroviral therapy (cART) has led to a significant reduction in the incidence of HIV-associated dementia (HAD). Despite these advances, the prevalence of HIV-1 associated neurocognitive disorders (HANDs) has been estimated at approximately 40%-50%. In t...


    pub_type: 杂志文章


    authors: Evering TH,Kamau E,St Bernard L,Farmer CB,Kong XP,Markowitz M

    更新日期:2014-08-15 00:00:00

  • Overlapping effector interfaces define the multiple functions of the HIV-1 Nef polyproline helix.

    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...


    pub_type: 杂志文章


    authors: Kuo LS,Baugh LL,Denial SJ,Watkins RL,Liu M,Garcia JV,Foster JL

    更新日期:2012-05-31 00:00:00

  • IFITM proteins are incorporated onto HIV-1 virion particles and negatively imprint their infectivity.

    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 ...


    pub_type: 杂志文章


    authors: Tartour K,Appourchaux R,Gaillard J,Nguyen XN,Durand S,Turpin J,Beaumont E,Roch E,Berger G,Mahieux R,Brand D,Roingeard P,Cimarelli A

    更新日期:2014-11-25 00:00:00

  • The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil.

    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...


    pub_type: 杂志文章,评审


    authors: Ishak R,de Oliveira Guimarães Ishak M,Vallinoto ACR

    更新日期:2020-02-14 00:00:00

  • Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody.

    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...


    pub_type: 杂志文章


    authors: Willett BJ,Kraase M,Logan N,McMonagle EL,Samman A,Hosie MJ

    更新日期:2010-04-26 00:00:00

  • DBR1 siRNA inhibition of HIV-1 replication.

    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...


    pub_type: 杂志文章


    authors: Ye Y,De Leon J,Yokoyama N,Naidu Y,Camerini D

    更新日期:2005-10-18 00:00:00

  • Generation and validation of a highly sensitive bioluminescent HIV-1 reporter vector that simplifies measurement of virus release.

    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...


    pub_type: 杂志文章


    authors: Kirui J,Freed EO

    更新日期:2020-05-19 00:00:00

  • Evidence against a role for jaagsiekte sheep retrovirus in human lung cancer.

    abstract:BACKGROUND:Jaagsiekte sheep retrovirus (JSRV) causes a contagious lung cancer in sheep and goats that can be transmitted by aerosols produced by infected animals. Virus entry into cells is initiated by binding of the viral envelope (Env) protein to a specific cell-surface receptor, Hyal2. Unlike almost all other retrov...


    pub_type: 杂志文章


    authors: Miller AD,De Las Heras M,Yu J,Zhang F,Liu SL,Vaughan AE,Vaughan TL,Rosadio R,Rocca S,Palmieri G,Goedert JJ,Fujimoto J,Wistuba II

    更新日期:2017-01-20 00:00:00

  • HIV-1 Rev oligomerization is not obligatory in the presence of an extra basic domain.

    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...


    pub_type: 杂志文章


    authors: Furnes C,Arnesen T,Askjaer P,Kjems J,Szilvay AM

    更新日期:2005-06-10 00:00:00

  • CD45 immunoaffinity depletion of vesicles from Jurkat T cells demonstrates that exosomes contain CD45: no evidence for a distinct exosome/HIV-1 budding pathway.

    abstract::The presence of relatively high levels of cellular protein contamination in density-purified virion preparations is a confounding factor in biochemical analyses of HIV and SIV produced from hematopoietic cells. A major source of this contamination is from vesicles, either microvesicles or exosomes, that have similar p...


    pub_type: 杂志文章


    authors: Coren LV,Shatzer T,Ott DE

    更新日期:2008-07-16 00:00:00

  • Analysis of herpes simplex type 1 gB, gD, and gH/gL on production of infectious HIV-1: HSV-1 gD restricts HIV-1 by exclusion of HIV-1 Env from maturing viral particles.

    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...


    pub_type: 杂志文章


    authors: Polpitiya Arachchige S,Henke W,Kalamvoki M,Stephens EB

    更新日期:2019-04-02 00:00:00

  • A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants.

    abstract:BACKGROUND:The recently approved anti-AIDS drug rilpivirine (TMC278, Edurant) is a nonnucleoside inhibitor (NNRTI) that binds to reverse transcriptase (RT) and allosterically blocks the chemical step of DNA synthesis. In contrast to earlier NNRTIs, rilpivirine retains potency against well-characterized, clinically rele...


    pub_type: 杂志文章


    authors: Johnson BC,Pauly GT,Rai G,Patel D,Bauman JD,Baker HL,Das K,Schneider JP,Maloney DJ,Arnold E,Thomas CJ,Hughes SH

    更新日期:2012-12-05 00:00:00

  • The inhibition of microRNAs by HIV-1 Tat suppresses beta catenin activity in astrocytes.

    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 ...


    pub_type: 杂志文章


    authors: Sardo L,Vakil PR,Elbezanti W,El-Sayed A,Klase Z

    更新日期:2016-04-08 00:00:00

  • TNPO3 protects HIV-1 replication from CPSF6-mediated capsid stabilization in the host cell cytoplasm.

    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...


    pub_type: 杂志文章


    authors: De Iaco A,Santoni F,Vannier A,Guipponi M,Antonarakis S,Luban J

    更新日期:2013-02-15 00:00:00

  • Induction of p21(CIP1/WAF1) expression by human T-lymphotropic virus type 1 Tax requires transcriptional activation and mRNA stabilization.

    abstract::HTLV-1 Tax can induce senescence by up-regulating the levels of cyclin-dependent kinase inhibitors p21(CIP1/WAF1) and p27(KIP1). Tax increases p27(KIP1) protein stability by activating the anaphase promoting complex/cyclosome (APC/C) precociously, causing degradation of Skp2 and inactivation of SCF(Skp2), the E3 ligas...


    pub_type: 杂志文章


    authors: Zhang L,Zhi H,Liu M,Kuo YL,Giam CZ

    更新日期:2009-04-08 00:00:00

  • Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors.

    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...


    pub_type: 杂志文章


    authors: Alam M,Kuwata T,Shimura K,Yokoyama M,Ramirez Valdez KP,Tanaka K,Maruta Y,Oishi S,Fujii N,Sato H,Matsuoka M,Matsushita S

    更新日期:2016-09-27 00:00:00

  • How to engage Cofilin.

    abstract::In HIV-infected people, resting CD4+ T cells are the main reservoir of latent virus and the reason for the failure of drug therapy to cure HIV infection. Still, we do not have a complete understanding of the factors regulating HIV replication in these cells. A recent paper in Cell describes a new trick that the virus ...


    pub_type: 杂志文章,评审


    authors: Bukrinsky M

    更新日期:2008-09-22 00:00:00

  • Functional analysis of human T lymphotropic virus type 2 Tax proteins.

    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...


    pub_type: 杂志文章


    authors: Sheehy N,Lillis L,Watters K,Lewis M,Gautier V,Hall W

    更新日期:2006-03-21 00:00:00

  • Inactivation of HIV-1 in breast milk by treatment with the alkyl sulfate microbicide sodium dodecyl sulfate (SDS).

    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...


    pub_type: 杂志文章


    authors: Urdaneta S,Wigdahl B,Neely EB,Berlin CM Jr,Schengrund CL,Lin HM,Howett MK

    更新日期:2005-04-29 00:00:00

  • The silent defense: micro-RNA directed defense against HIV-1 replication.

    abstract::MicroRNAs play critical role in regulating gene expression. MicroRNA profile of particular cell type bears the signature of cell type specific gene expression. Given that viral pathogens replicate by evading host defenses, research is now focused on the miRNA-regulated genes that critically regulate HIV-1 propagation ...


    pub_type: 杂志文章


    authors: Kumar A

    更新日期:2007-04-12 00:00:00

  • A purine-rich element in foamy virus pol regulates env splicing and gag/pol expression.

    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...


    pub_type: 杂志文章


    authors: Moschall R,Denk S,Erkelenz S,Schenk C,Schaal H,Bodem J

    更新日期:2017-02-06 00:00:00

  • Low-level alternative tRNA priming of reverse transcription of HIV-1 and SIV in vivo.

    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...


    pub_type: 杂志文章


    authors: Fennessey CM,Camus C,Immonen TT,Reid C,Maldarelli F,Lifson JD,Keele BF

    更新日期:2019-04-04 00:00:00

  • Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy.

    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...


    pub_type: 杂志文章


    authors: Chugh P,Bradel-Tretheway B,Monteiro-Filho CM,Planelles V,Maggirwar SB,Dewhurst S,Kim B

    更新日期:2008-01-31 00:00:00

  • Establishment of a novel diagnostic test algorithm for human T-cell leukemia virus type 1 infection with line immunoassay replacement of western blotting: a collaborative study for performance evaluation of diagnostic assays in Japan.

    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...


    pub_type: 杂志文章


    authors: Okuma K,Kuramitsu M,Niwa T,Taniguchi T,Masaki Y,Ueda G,Matsumoto C,Sobata R,Sagara Y,Nakamura H,Satake M,Miura K,Fuchi N,Masuzaki H,Okayama A,Umeki K,Yamano Y,Sato T,Iwanaga M,Uchimaru K,Nakashima M,Utsunomiya A

    更新日期:2020-08-24 00:00:00

  • Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP.

    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...


    pub_type: 杂志文章


    authors: Naito T,Yasunaga JI,Mitobe Y,Shirai K,Sejima H,Ushirogawa H,Tanaka Y,Nakamura T,Hanada K,Fujii M,Matsuoka M,Saito M

    更新日期:2018-11-06 00:00:00