Probes for INS
ACD can configure probes for the various manual and automated assays for INS for RNAscope Assay, or for Basescope Assay compatible for your species of interest.
- Probes for INS (0)
- Kits & Accessories (0)
- Support & Documents (0)
- Publications (62)
- Image gallery (0)
Refine Probe List
AIDS research and human retroviruses
2023 Apr 26
Sanders-Beer, BE;Archin, NM;Brumme, ZL;Busch, M;Deleage, C;O'Doherty, U;Hughes, SH;Jerome, K;Jones, RB;Karn, J;Kearney, MF;Keele, B;Kulpa, D;Laird, G;Li, JZ;Lichterfeld, M;Nussenzweig, MC;Persaud, D;Yukl, S;Siliciano, RF;Mellors, JW;
PMID: 37126090 | DOI: 10.1089/AID.2022.0188
Since the first HIV-cured person was reported in 2009, a strong interest in developing highly sensitive HIV and SIV reservoir assays has emerged. In particular, the question arose about the comparative value of state-of-the-art assays to measure and characterize the HIV reservoir, and how these assays can be applied to accurately detect changes in the reservoir during efforts to develop a cure for HIV infection. Secondly, it is important to consider the impact on the outcome of clinical trials if these relatively new HIV reservoir assays are incorporated into clinical trial endpoints and/or used for clinical decision-making. To understand the advantages and limitations and the regulatory implications of HIV reservoir assays, the National Institute of Allergy and Infectious Diseases (NIAID) sponsored and convened a meeting on September 16, 2022, to discuss the state of knowledge concerning these questions and best practices for selecting HIV reservoir assays for a particular research question or clinical trial protocol.
Nature medicine
2023 Feb 20
Jensen, BO;Knops, E;Cords, L;Lübke, N;Salgado, M;Busman-Sahay, K;Estes, JD;Huyveneers, LEP;Perdomo-Celis, F;Wittner, M;Gálvez, C;Mummert, C;Passaes, C;Eberhard, JM;Münk, C;Hauber, I;Hauber, J;Heger, E;De Clercq, J;Vandekerckhove, L;Bergmann, S;Dunay, GA;Klein, F;Häussinger, D;Fischer, JC;Nachtkamp, K;Timm, J;Kaiser, R;Harrer, T;Luedde, T;Nijhuis, M;Sáez-Cirión, A;Schulze Zur Wiesch, J;Wensing, AMJ;Martinez-Picado, J;Kobbe, G;
PMID: 36807684 | DOI: 10.1038/s41591-023-02213-x
Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.
Cell reports
2022 May 31
Foreman, TW;Nelson, CE;Kauffman, KD;Lora, NE;Vinhaes, CL;Dorosky, DE;Sakai, S;Gomez, F;Fleegle, JD;Parham, M;Perera, SR;Lindestam Arlehamn, CS;Sette, A;Tuberculosis Imaging Program, ;Brenchley, JM;Queiroz, ATL;Andrade, BB;Kabat, J;Via, LE;Barber, DL;
PMID: 35649361 | DOI: 10.1016/j.celrep.2022.110896
HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of tuberculosis prior to loss of peripheral CD4 T cells, raising the possibility that HIV co-infection leads to CD4 T cell depletion in lung tissue before it is evident in blood. Here, we use rhesus macaques to study the early effects of simian immunodeficiency virus (SIV) co-infection on pulmonary granulomas. Two weeks after SIV inoculation of Mtb-infected macaques, Mtb-specific CD4 T cells are dramatically depleted from granulomas, before CD4 T cell loss in blood, airways, and lymph nodes, or increases in bacterial loads or radiographic evidence of disease. Spatially, CD4 T cells are preferentially depleted from the granuloma core and cuff relative to B cell-rich regions. Moreover, live imaging of granuloma explants show that intralesional CD4 T cell motility is reduced after SIV co-infection. Thus, granuloma CD4 T cells may be decimated before many co-infected individuals experience the first symptoms of acute HIV infection.
Journal of Virus Eradication
2022 Dec 01
Collins, D;Hitschfel, J;Walker, B;
| DOI: 10.1016/j.jve.2022.100202
Background: HIV infection persists predominantly within follicular helper CD4+ T cell-rich B cell follicles of lymphoid tissues. Cytotoxic CD8+ T cells, which are associated with natural control of HIV infection in peripheral blood, are relatively excluded from this niche, representing a potential barrier to cellular immunity and HIV cure. To better understand the mechanisms of HIV control within lymph nodes (LN), we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics and transcriptional profiles of LN-resident virus-specific and CXCR5-expressing follicular CD8+ T cells (fCD8) in persons who control HIV without medications. Methods: We obtained paired excisional inguinal LN biopsies and peripheral blood (PB) from 19 spontaneous HIV controllers and 17 HIV+ individuals on long-term ART. HIV-specific CD8+ T cell responses were identified by IFN-γ ELISpot and functional response to antigenic stimulation was measured by flow cytometry and CFSE-based proliferation assay. Clonotypic compartmentalization and transcriptional signatures associated with localization of HIV-specific CD8+ T cells were assessed via TCR and RNA-sequencing. Spatial relationships between ongoing viral replication and fCD8 cytotoxic effector potential in GCs were measured by HIV gagpol RNAscope and immunofluorescence on fixed LN sections. Results: Antigen-induced HIV-specific CD8+ T cell proliferation and cytolytic effector upregulation consistently distinguished spontaneous controllers from noncontrollers in PB (p=0.03) and LN (p=0.04). HIV-specific CD8+ T cells from both compartments shared TCR clonotypic composition (Morisita-Horn Similarity Index 0.8-1.0), consistent with ongoing infiltration from circulation. Migration into LNs was associated with gene signatures of inflammatory chemotaxis and antigen-induced effector function. The cytolytic effectors perforin and granzyme B were elevated among virus-specific CXCR5 + fCD8 s (p
Viruses
2022 Sep 09
Byrnes, SJ;Angelovich, TA;Busman-Sahay, K;Cochrane, CR;Roche, M;Estes, JD;Churchill, MJ;
PMID: 36146803 | DOI: 10.3390/v14091997
Human Immunodeficiency virus (HIV)-associated neurocognitive disorders are a major burden for people living with HIV whose viremia is stably suppressed with antiretroviral therapy. The pathogenesis of disease is likely multifaceted, with contributions from viral reservoirs including the brain, chronic and systemic inflammation, and traditional risk factors including drug use. Elucidating the effects of each element on disease pathogenesis is near impossible in human clinical or ex vivo studies, facilitating the need for robust and accurate non-human primate models. In this review, we describe the major non-human primate models of neuroHIV infection, their use to study the acute, chronic, and virally suppressed infection of the brain, and novel therapies targeting brain reservoirs and inflammation.
Science immunology
2023 May 19
Collins, DR;Hitschfel, J;Urbach, JM;Mylvaganam, GH;Ly, NL;Arshad, U;Racenet, ZJ;Yanez, AG;Diefenbach, TJ;Walker, BD;
PMID: 37205767 | DOI: 10.1126/sciimmunol.ade5872
Follicular CD8+ T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but the precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8+ T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8+ T cells. Transcriptional analysis of LN CD8+ T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5+ fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s.
Current HIV/AIDS reports
2023 Jan 23
George, AF;Roan, NR;
PMID: 36689119 | DOI: 10.1007/s11904-023-00649-x
This review describes how advances in CyTOF and high-dimensional analysis methods have furthered our understanding of HIV transmission, pathogenesis, persistence, and immunity.CyTOF has generated important insight on several aspects of HIV biology: (1) the differences between cells permissive to productive vs. latent HIV infection, and the HIV-induced remodeling of infected cells; (2) factors that contribute to the persistence of the long-term HIV reservoir, in both blood and tissues; and (3) the impact of HIV on the immune system, in the context of both uncontrolled and controlled infection. CyTOF and high-dimensional analysis tools have enabled in-depth assessment of specific host antigens remodeled by HIV, and have revealed insights into the features of HIV-infected cells enabling them to survive and persist, and of the immune cells that can respond to and potentially control HIV replication. CyTOF and other related high-dimensional phenotyping approaches remain powerful tools for translational research, and applied HIV to cohort studies can inform on mechanisms of HIV pathogenesis and persistence, and potentially identify biomarkers for viral eradication or control.
Viruses
2023 Jan 27
Abeynaike, S;Huynh, T;Mehmood, A;Kim, T;Frank, K;Gao, K;Zalfa, C;Gandarilla, A;Shultz, L;Paust, S;
| DOI: 10.3390/v15020365
Mice reconstituted with human immune systems are instrumental in the investigation of HIV-1 pathogenesis and therapeutics. Natural killer (NK) cells have long been recognized as a key mediator of innate anti-HIV responses. However, established humanized mouse models do not support robust human NK cell development from engrafted human hematopoietic stem cells (HSCs). A major obstacle to human NK cell reconstitution is the lack of human interleukin-15 (IL-15) signaling, as murine IL-15 is a poor stimulator of the human IL-15 receptor. Here, we demonstrate that immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice expressing a transgene encoding human IL-15 (NSG-Tg(IL-15)) have physiological levels of human IL-15 and support long-term engraftment of human NK cells when transplanted with human umbilical-cord-blood-derived HSCs. These Hu-NSG-Tg(IL-15) mice demonstrate robust and long-term reconstitution with human immune cells, but do not develop graft-versus-host disease (GVHD), allowing for long-term studies of human NK cells. Finally, we show that these HSC engrafted mice can sustain HIV-1 infection, resulting in human NK cell responses in HIV-infected mice. We conclude that Hu-NSG-Tg(IL-15) mice are a robust novel model to study NK cell responses to HIV-1.
Immunity
2022 Apr 12
Jiang, S;Chan, CN;Rovira-Clavé, X;Chen, H;Bai, Y;Zhu, B;McCaffrey, E;Greenwald, NF;Liu, C;Barlow, GL;Weirather, JL;Oliveria, JP;Nakayama, T;Lee, IT;Matter, MS;Carlisle, AE;Philips, D;Vazquez, G;Mukherjee, N;Busman-Sahay, K;Nekorchuk, M;Terry, M;Younger, S;Bosse, M;Demeter, J;Rodig, SJ;Tzankov, A;Goltsev, Y;McIlwain, DR;Angelo, M;Estes, JD;Nolan, GP;
PMID: 35447093 | DOI: 10.1016/j.immuni.2022.03.020
Understanding the mechanisms of HIV tissue persistence necessitates the ability to visualize tissue microenvironments where infected cells reside; however, technological barriers limit our ability to dissect the cellular components of these HIV reservoirs. Here, we developed protein and nucleic acid in situ imaging (PANINI) to simultaneously quantify DNA, RNA, and protein levels within these tissue compartments. By coupling PANINI with multiplexed ion beam imaging (MIBI), we measured over 30 parameters simultaneously across archival lymphoid tissues from healthy or simian immunodeficiency virus (SIV)-infected nonhuman primates. PANINI enabled the spatial dissection of cellular phenotypes, functional markers, and viral events resulting from infection. SIV infection induced IL-10 expression in lymphoid B cells, which correlated with local macrophage M2 polarization. This highlights a potential viral mechanism for conditioning an immunosuppressive tissue environment for virion production. The spatial multimodal framework here can be extended to decipher tissue responses in other infectious diseases and tumor biology.
Microbiology spectrum
2021 Oct 31
Janssens, J;Blokken, J;Lampi, Y;De Wit, F;Zurnic Bonisch, I;Nombela, I;Van de Velde, P;Van Remoortel, B;Gijsbers, R;Christ, F;Debyser, Z;
PMID: 34612665 | DOI: 10.1128/Spectrum.01336-21
To infect nondividing cells, HIV-1 needs to cross the nuclear membrane. The importin transportin-SR2 (TRN-SR2 or transportin-3) has been proposed to mediate HIV-1 nuclear import, but the detailed mechanism remains unresolved. The direct interaction of TRN-SR2 with HIV-1 integrase (IN) has been proposed to drive HIV-1 nuclear import. Alternatively, TRN-SR2 may play an indirect role by mediating nuclear import of cleavage and polyadenylation specificity factor 6 (CPSF6). To unravel the role of TRN-SR2, we designed CRISPR/Cas9 guide RNAs targeting different exons of TNPO3. Although this approach failed to generate full knockouts, monoallelic knockout clones were generated with indel mutations. HIV-1 replication was hampered in those clones at the level of HIV-1 nuclear import without an effect on the cellular distribution of the TRN-SR2 cargoes CPSF6 or alternative splicing factor1/pre-mRNA splicing factor SF2 (ASF/SF2). Recombinant ΔV105 TRN-SR2 expressed in clone 15.15 was 2-fold impaired for interaction with HIV-1 IN and classified as an interaction mutant. Our data support a model whereby TRN-SR2 acts as a cofactor of HIV-1 nuclear import without compromising the nuclear import of cellular cargoes. CRISPR/Cas9-induced mutagenesis can be used as a method to generate interface mutants to characterize host factors of human pathogens. IMPORTANCE Combination antiretroviral therapy (cART) effectively controls HIV-1 by reducing viral loads, but it does not cure the infection. Lifelong treatment with cART is a prerequisite for sustained viral suppression. The rapid emergence of drug-resistant viral strains drives the necessity to discover new therapeutic targets. The nuclear import of HIV-1 is crucial in the HIV-1 replication cycle, but the detailed mechanism remains incompletely understood. This study provides evidence that TRN-SR2 directly mediates HIV-1 nuclear import via the interaction with HIV-1 integrase. The interaction between those proteins is therefore a promising target toward a rational drug design which could lead to new therapeutic strategies due to the bottleneck nature of HIV-1 nuclear import.
Cell reports
2022 Sep 20
Baharlou, H;Canete, N;Vine, EE;Hu, K;Yuan, D;Sandgren, KJ;Bertram, KM;Nasr, N;Rhodes, JW;Gosselink, MP;Di Re, A;Reza, F;Ctercteko, G;Pathma-Nathan, N;Collins, G;Toh, J;Patrick, E;Haniffa, MA;Estes, JD;Byrne, SN;Cunningham, AL;Harman, AN;
PMID: 36130503 | DOI: 10.1016/j.celrep.2022.111385
The initial immune response to HIV determines transmission. However, due to technical limitations we still do not have a comparative map of early mucosal transmission events. By combining RNAscope, cyclic immunofluorescence, and image analysis tools, we quantify HIV transmission signatures in intact human colorectal explants within 2 h of topical exposure. We map HIV enrichment to mucosal dendritic cells (DCs) and submucosal macrophages, but not CD4+ T cells, the primary targets of downstream infection. HIV+ DCs accumulate near and within lymphoid aggregates, which act as early sanctuaries of high viral titers while facilitating HIV passage to the submucosa. Finally, HIV entry induces recruitment and clustering of target cells, facilitating DC- and macrophage-mediated HIV transfer and enhanced infection of CD4+ T cells. These data demonstrate a rapid response to HIV structured to maximize the likelihood of mucosal infection and provide a framework for in situ studies of host-pathogen interactions and immune-mediated pathologies.
iScience
2022 Nov 01
Shah, R;Gallardo, C;Jung, Y;Clock, B;Dixon, J;McFadden, W;Majumder, K;Pintel, D;Corces, V;Torbett, B;Tedbury, P;Sarafianos, S;
| DOI: 10.1016/j.isci.2022.105490
It is unclear how the activation of HIV-1 transcription affects chromatin structure. We interrogated chromatin organization both genome-wide and nearby HIV-1 integration sites using Hi-C and ATAC-seq. In conjunction, we analyzed the transcription of the HIV-1 genome and neighboring genes. We found that long-range chromatin contacts did not differ significantly between uninfected cells and those harboring an integrated HIV-1 genome, whether the HIV-1 genome was actively transcribed or inactive. Instead, the activation of HIV-1 transcription changes chromatin accessibility immediately downstream of the provirus, demonstrating that HIV-1 can alter local cellular chromatin structure. Finally, we examined HIV-1 and neighboring host gene transcripts with long-read sequencing and found populations of chimeric RNAs both virus-to-host and host-to-virus. Thus, multiomics profiling revealed that the activation of HIV-1 transcription led to local changes in chromatin organization and altered the expression of neighboring host genes.
Pages
X
| Description | ||
|---|---|---|
| sense Example: Hs-LAG3-sense | Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe. | |
| Intron# Example: Mm-Htt-intron2 | Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection | |
| Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G) | A mixture of multiple probe sets targeting multiple genes or transcripts | |
| No-XSp Example: Hs-PDGFB-No-XMm | Does not cross detect with the species (Sp) | |
| XSp Example: Rn-Pde9a-XMm | designed to cross detect with the species (Sp) | |
| O# Example: Mm-Islr-O1 | Alternative design targeting different regions of the same transcript or isoforms | |
| CDS Example: Hs-SLC31A-CDS | Probe targets the protein-coding sequence only | |
| EnEm | Probe targets exons n and m | |
| En-Em | Probe targets region from exon n to exon m | |
| Retired Nomenclature | ||
| tvn Example: Hs-LEPR-tv1 | Designed to target transcript variant n | |
| ORF Example: Hs-ACVRL1-ORF | Probe targets open reading frame | |
| UTR Example: Hs-HTT-UTR-C3 | Probe targets the untranslated region (non-protein-coding region) only | |
| 5UTR Example: Hs-GNRHR-5UTR | Probe targets the 5' untranslated region only | |
| 3UTR Example: Rn-Npy1r-3UTR | Probe targets the 3' untranslated region only | |
| Pan Example: Pool | A mixture of multiple probe sets targeting multiple genes or transcripts | |
- Toll-free in the US and Canada
- +1877 576-3636
X
Contact Us
Complete one of the three forms below and we will get back to you.
For Quote Requests, please provide more details in the Contact Sales form below
Advanced Cell Diagnostics
Our new headquarters office starting May 2016:
7707 Gateway Blvd.
Newark, CA 94560
Toll Free: 1 (877) 576-3636
Phone: (510) 576-8800
Fax: (510) 576-8798
Bio-Techne
19 Barton Lane
Abingdon Science Park
Abingdon
OX14 3NB
United Kingdom
Phone 2: +44 1235 529449
Fax: +44 1235 533420
Advanced Cell Diagnostics China
20F, Tower 3,
Raffles City Changning Office,
1193 Changning Road, Shanghai 200051
021-52293200
info.cn@bio-techne.com
Web: www.acdbio.com/cn
For general information: Info.ACD@bio-techne.com
For place an order: order.ACD@bio-techne.com
For product support: support.ACD@bio-techne.com
For career opportunities: hr.ACD@bio-techne.com
×
You have already Quick ordered an Item in your cart . If you want to add a new item , Quick ordered Item will be removed form your cart. Do You want to continue?
OK Cancel