Cells respond to diverse stimuli, which include physiological agents such as growth factors (reviewed in Bravo, 1990; Marshall, 1994) and cytokines (Freshney et al., 1994; Sluss et al., 1994), pharmacological compounds such as anisomycin (Edwards and Mahadevan, 1992; Hazzalin et al., 1998, and references therein), phorbol esters and okadaic acid (reviewed in Cohen, 1990; Cano et al., 1995) and stresses such as UV radiation (Hibi et al., 1993; Kyriakis et al., 1994), hyperosmotic (Han et al., 1994; Rosette and Karin, 1996) and heavy metal stress (Rouse et al., 1994, and references therein) by initiating intracellular signalling mechanisms that rapidly elicit transcription of a subset of genes in the nucleus (reviewed in Karin, 1994; Cano and Mahadevan, 1995; Treisman, 1996; Hazzalin et al., 1998). These genes, called immediate‐early (IE) genes, are activated directly and require no new transcription or translation for their induction (Greenberg et al., 1986; Almendral et al., 1988; reviewed in ...

The function of striatopallidal neurons is regulated by N-methyl-d-aspartate (NMDA) and dopamine D2 receptors. Previous studies show that immediate early gene induction by D2 receptor blockade is suppressed by NMDA receptor antagonists. Because the pharmacology of NMDA receptors depends on the incorporation of different NR2 subunits and NR2 subunits show regional and cellular differences in their expression in striatum, our study examined whether different NMDA receptor antagonists would have differential effects on eticlopride-induced immediate early gene expression in striatum. Male Sprague-Dawley rats were pretreated with vehicle, CGS 19755, MK-801 or ifenprodil. Rats then received injections of eticlopride and were killed 40 min later. In situ hybridization histochemistry was used to determine the expression of c-fos andzif268 in the striatum. Eticlopride increased immediate early gene expression in striatum, with the increase generally being greater in lateral than in medial striatum. ...

Excessive extracellular glutamate triggers delayed neuronal death by promoting the influx of calcium into cells by activating N-methyl-D-aspartate (NMDA) or non-NMDA glutamate receptors. [4] Glutamate receptor activation, in turn, stimulates expression of rapidly induced transcriptional activators known as the immediate-early genes. These genes initiate a complex cascade of events that transduct extracellular signals into alterations of cellular functions by regulating target gene expression (late-response genes). [5-7] The immediate-early gene c-fos is rapidly and transiently induced in neurons within the hippocampal formation of the brain after seizures, hypoxia, and global ischemia through glutamate-mediated NMDA and non-NMDA receptor activation. [8-10] The protein product of c-fos mRNA, FOS, modulates transcription of several late-response genes, such as p53, heat-shock protein, bcl-x, tyrosine hydroxylase, and opioid peptides. [10-12] Some of the late-response genes expressed after c-fos ...

BACKGROUND: Extracellular signaling through receptors for neurotrophins mediates diverse neuronal functions, including survival, migration and differentiation in the central nervous system, but the transcriptional targets and regulators that mediate these diverse neurotrophin functions are not well understood. RESULTS: We have identified the immediate-early (IE) genes Fos, Egr1 and Egr2 as transcriptional targets of brain derived neurotrophic factor (BDNF)/TrkB signaling in primary cortical neurons, and show that the Fos serum response element area responds to BDNF/TrkB in a manner dependent on a combined C/EBP-Ebox element. The Egr1 and Egr2 promoters contain homologous regulatory elements. We found that C/EBPalpha/beta and NeuroD formed complexes in vitro and in vivo, and were recruited to all three homologous promoter regions. C/EBPalpha and NeuroD co-operatively activated the Fos promoter in transfection assays. Genetic depletion of Trk receptors led to impaired recruitment of C/EBPs and NeuroD in

Immediate-early genes have important roles in processes such as brain development, learning, and responses to drug abuse. Further, immediate-early genes play an essential role in cellular responses that contribute to long-term neuronal plasticity. Neuronal plasticity is a characteristic of the nervo …

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Research in our laboratory is focused on providing a more complete understanding of the cellular and molecular mechanisms involved in cognition and memory storage in the mammalian brain. Specifically, we are interested in the role that immediate-early genes (IEGs) induced by neural activated associated with learning play in stabilizing neural networks to ultimately encode long-term memories. These studies require a multidisciplinary approach, using methods from molecular biology, biochemistry, and systems- and behavioral neuroscience. Our work can be divided broadly into 3 main areas: 1) Determining the molecular and systems interactions regulating IEG expression following learning, 2) Identifying the role of different IEGs to neuroplastic processes, and 3) Using advanced IEG imaging methods to define neuronal population interactions involved in learning and memory. This research will increase understanding of the neurobiological bases of memory, and may provide the basis for future advances in ...

Cellular stimulation causes the rapid appearance of proteins in the nucleus which function as signal-regulated transcription factors converting membrane events into long-term changes in gene...

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. It is most closely related to MAPK8, both of which are involved in UV radiation induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway. This gene and MAPK8 are also known as c-Jun N-terminal kinases. This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells. Studies of this genes mouse counterpart suggest a key role in T-cell differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported ...

OG-L002 is a potent selective LSD1 inhibitor, it also inhibits inhibitor MAO-A and MAO-B. OG-L002 inhibits the HSV IE gene expression in vitro and in vivo.

The repression of human cytomegalovirus immediate-early (IE) lytic gene expression is crucial for the maintenance of the latent viral state. By using conditionally permissive cell lines, which provide a good model for the differentiation state-dependent repression of IE gene expression, we have identified several cellular factors that bind to the major immediate-early promoter (MIEP) and whose expression is down-regulated after differentiation to a permissive phenotype. Here we show that the cellular protein Ets-2 Repressor Factor (ERF) physically interacts with the MIEP and represses MIEP activity in undifferentiated non-permissive T2 embryonal carcinoma cells. This factor binds to the dyad element and the 21 bp repeats within the MIEP - regions known to be important for the negative regulation of MIEP activity. Finally, we show that following differentiation to a permissive phenotype ERF's repressive effects are severely abrogated.

We previously demonstrated that APP epigenetically regulates Egr1 expression both in cultured neurons and in vivo. Since Egr1 is an immediate early gene involved in memory formation, we wondered whether other early genes involved in memory were regulated by APP and we studied molecular mechanisms involved. By comparing prefrontal (PF) cortex from wild type (APP+/+) and APP knockout mice (APP-/-), we observed that APP down regulates expression of four immediate early genes, Egr1, c-Fos, Bdnf and Arc. Down regulation of Egr1, c-Fos and Bdnf transcription resulted from a decreased enrichment of acetylated histone H4 on the corresponding gene promoter. Further characterization of H4 acetylation at Egr1 and c-Fos promoters revealed increased acetylation of H4K5 and H4K12 residues in APP-/- mice. Whereas APP affected Egr1 promoter activity by reducing access of the CREB transcription factor, its effect on c-Fos appeared to depend on increased recruitment of HDAC2 histone deacetylase to the gene ...

Therapeutic irradiation can induce cognitive impairments without necessarily causing the gross histologic disruption classically associated with exposure to high radiation doses ( 1). Given that postmitotic neurons are generally considered to be relatively radioresistant, new approaches/techniques have been used to identify other targets that may ultimately contribute to the pathogenesis of radiation-induced cognitive injury. Data now exist regarding neurogenesis ( 14, 15), specific genetic factors ( 33) or receptor expression ( 34), and show that changes in these end points can be associated with subsequent cognitive impairments. Still, there is considerable uncertainty regarding how molecular and cellular events within specific neuronal populations are translated into changes that affect behavioral performance. Understanding such changes will be critical to the development of strategies or approaches necessary to prevent or treat the cognitive changes induced by therapeutic irradiation of ...

1. MocarskiES. ShenkT. PassRF. 2007 Cytomegaloviruses. KnipeDM. HowleyPM. GriffinDE. LambRA. MartinMA. RoizmanB. StrausSE. Fields virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA 2701 2772. 2. MeierJL. StinskiMF. 2006 Major immediate-early enhancer and its gene products. In Cytomegaloviruses: Molecular Biology and Immunology ed. ReddehaseM. Norfolk Caister Academic Press 151 166. 3. BegoM. MaciejewskiJ. KhaiboullinaS. PariG. St JeorS. 2005 Characterization of an antisense transcript spanning the UL81-82 locus of human cytomegalovirus. J Virol 79 11022 11034. 4. KondoK. XuJ. MocarskiES. 1996 Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals. Proc Natl Acad Sci U S A 93 11137 11142. 5. PetrucelliA. RakM. GraingerL. GoodrumF. 2009 Characterization of a novel Golgi apparatus-localized latency determinant encoded by human cytomegalovirus. J Virol 83 5615 5629. 6. JenkinsC. AbendrothA. SlobedmanB. 2004 A novel ...

Shop Immediate-early protein ELISA Kit, Recombinant Protein and Immediate-early protein Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.

DNA-binding protein that seems to act as a transcription factor (By similarity). Involved in the regulation of neuronal differentiation, acts upon JNK-signaling pathway activation and plays a role in neurite outgrowth in hippocampal cells (PubMed:17156131). May mediate with FIBP FGF-signaling in the establishment of laterality in the embryo (By similarity). Promotes cell motility, seems to stimulate tumor metastasis (By similarity).

The honeybee is a social insect that exhibits various social behaviors. To elucidate the neural basis of honeybee behavior, we detected neural activity in freely-moving honeybee workers using an immediate early gene (IEG) that is expressed in a neural activity-dependent manner. In European honeybees (Apis mellifera), we identified a novel nuclear non-coding RNA, termed kakusei, as the first insect IEG, and revealed the neural activity pattern in foragers. In addition, we isolated a homologue of kakusei, termed Acks, from the Japanese honeybee (Apis cerana), and detected active neurons in workers fighting with the giant hornet.

Contains the human cytomegalovirus immediate-early enhancer/promoter region for strong, constitutive expression of cloned DNA inserts in a variety of mammalian cell types.

Das Immediate-Early Protein 2 (IE2) des humanen Zytomegalievirus ist ein essentieller Regulationsfaktor des lytischen Infektionszyklus. Es aktiviert verschiedene early Promotoren, autoreprimiert seine eigene Expression und besitzt darüber hinaus auch zellzyklusregulatorische Aktivitäten. Um einzelne Funktionen des IE2 Proteins gezielt analysieren zu können, ist eine genaue Kenntnis seiner regulatorischen Domänen unabdingbar. Im Rahmen dieser Arbeit wurde daher eine Struktur-Funktionsanalyse des IE2 Proteins durchgeführt mit dem Ziel, seine funktionellen Domänen genauer zu charakterisieren. Hierfür wurden verschiedene IE2-Mutanten hergestellt und ihre Aktivität im Hinblick auf Transaktivierung, Autorepression und DNA-Bindung sowie Zellzylusarrestinduktion bestimmt. Die Untersuchungen ergaben, dass innerhalb einer Core-Region im C-Terminus des Proteins (AS 450-544) die regulatorischen Domänen der untersuchten Funktionen überlappen und hier schon kleinere Mutationen zu einem ...

Das Immediate-Early Protein 2 (IE2) des humanen Zytomegalievirus ist ein essentieller Regulationsfaktor des lytischen Infektionszyklus. Es aktiviert verschiedene early Promotoren, autoreprimiert seine eigene Expression und besitzt darüber hinaus auch zellzyklusregulatorische Aktivitäten. Um einzelne Funktionen des IE2 Proteins gezielt analysieren zu können, ist eine genaue Kenntnis seiner regulatorischen Domänen unabdingbar. Im Rahmen dieser Arbeit wurde daher eine Struktur-Funktionsanalyse des IE2 Proteins durchgeführt mit dem Ziel, seine funktionellen Domänen genauer zu charakterisieren. Hierfür wurden verschiedene IE2-Mutanten hergestellt und ihre Aktivität im Hinblick auf Transaktivierung, Autorepression und DNA-Bindung sowie Zellzylusarrestinduktion bestimmt. Die Untersuchungen ergaben, dass innerhalb einer Core-Region im C-Terminus des Proteins (AS 450-544) die regulatorischen Domänen der untersuchten Funktionen überlappen und hier schon kleinere Mutationen zu einem ...

The pCI Vector contains the CMV immediate-early enhancer/promoter region and is designed to promote constitutive expression of cloned DNA inserts in mammalian cells.

CYR61 is a growth factor-inducible, immediate-early gene that has multifaceted activities in various cancers.CYR61 is a secreted, cysteine-rich, heparin-binding protein.

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Leucémie Lymphoide Chronique et Macroglobulinémie de Waldenström Delmer, Alain;Feugier, Pierre John Libbey Eurotext Limited 2018 3e édition.

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A set of immediate-early genes that are rapidly activated by serum or purified platelet-derived growth factor in mouse 3T3 fibroblasts has been previously identified. Among these genes, several are related to known or putative transcription factors and growth factors, supporting the notion that some of these genes encode regulatory molecules important to cell growth. We show here that a member of this set of genes, cyr61 (originally identified by its cDNA 3CH61), encodes a 379-amino-acid polypeptide rich in cysteine residues. cyr61 can be induced through protein kinase C-dependent and -independent pathways. Unlike many immediate-early genes that are transiently expressed, the cyr61 mRNA is accumulated from the G0/G1 transition through mid-G1. This expression pattern is due to persistent transcription, while the mRNA is rapidly turned over during the G0/G1 transition and in mid-G1 at the same rate. In logarithmically growing cells, the cyr61 mRNA level is constant throughout the cell cycle.

Human cytomegalovirus (HCMV) is a frequent cause of major disease following primary infection or reactivation from latency in immunocompromised patients. Infection of non-permissive mononuclear cells is used for analyses of HCMV latency in vitro. Using this approach, it is shown here that repression of lytic gene expression following experimental infection of CD34+ cells, a site of HCMV latency in vivo, correlates with recruitment of repressive chromatin around the major immediate-early promoter (MIEP). Furthermore, long-term culture of CD34+ cells results in carriage of viral genomes in which the MIEP remains associated with transcriptionally repressive chromatin. Finally, specific differentiation of long-term cultures of infected CD34+ cells to mature dendritic cells results in acetylation of histones bound to the MIEP, concomitant loss of heterochromatin protein 1 and the reactivation of HCMV. These data are consistent with ex vivo analyses of latency and may provide a model for further analyses of

Human cytomegalovirus (HCMV) was first isolated 50 years ago, when the new technology of cell culture became available. The pathogenesis of HCMV disease is complex, involving contributions from the host as well as from the virus. Increasing knowledge about the genetic composition of the virus can help to illuminate this complex series of relationships and provide a rational basis for therapeutic intervention and prevention of disease. The major immediate-early promoter (MIEP) enhancer contains multiple recognition sites for the transcription factors. Additionally, the MIEP is specifically transactivated by the tegument protein pp71, which is released as soon as incoming virions are uncoated. Thus, HCMV employs multiple methods independent of de novo viral gene expression to induce an intracellular milieu favorable to the initiation of immediate-early (IE) gene transcription. Humoral immunity could reduce the level of HCMV replication and reduce disease without being able to eliminate infection entirely.

and 20 disease-causing mutations responsible for ID. Our most important scientific accomplishments include (i) the identification of neurotrypsin as the first non-syndromic autosomal recessive ID gene, linking impaired brain plasticity and defects in extracellular proteolytic activity at the synapse; (ii) the identification of the TUSC3 gene, emphasizing the crucial role of N-glycosylation in higher brain function; (iii) the identification of the MED23 gene, highlighting the key role of the Mediator in brain development and functioning and suggesting that altered IEG expression might be a molecular hallmark of cognitive deficit; (iv) the demonstration that members of the Drosophila Behaviour Human Splicing (DBHS) protein family play a key role in inhibitory synapse biology.. 2. Evaluate the role of epigenomic variations in the etiology of ASD ...

The immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers.

Human cytomegalovirus (HCMV), a member of the herpesvirus group, is species specific and can establish both persistent and latent infections. The virus appears to be able to infect a number of cell...

Many other examples can be found in this review by Jack Keene. I dont think Ive seen an example of this yet, but given the slight wobble in microRNA specificity, one could imagine a single microRNA regulating a whole set of genes. Also, most interesting for my neuro-tastes is the recent report from the Moore lab showing that the immediate-early gene implicated in neuronal homeostasis, Arc, may be part of a regulon defined by introns in the 3UTR. The mechanism is just too clever but requires an explication on the pioneer round of translation. Basically the cell tricks itself into thinking it made a funky RNA and destroys it after one round of synthesis. The other RNAs regulated in this path in neurons must have opposing effects to Arc though because knocking down this negative regulation pathway led to increased excitability (increased Arc reduces neuronal excitability). This raises a more general question. The idea of RNA regulons is nice, but how much can you predict knowing that your gene ...

The immediate-early gene of herpesvirus saimiri has homology with murine superantigens. removed. The deletion mutants of stress C488 14 and 14-4.6 which absence a lot of the coding series were generated in independent tests to be able to minimize any bias from spontaneous mutations elsewhere in the herpesvirus genome (3 5 11 After acceptance with the Institutional Pet Treatment and Use Committee (Biomedical Analysis Centre Rijswijk HOLLAND) wild-type C488 and mutants 14-3.11 and 14-4.6 GSK 525762A (107 PFU in 1 ml of cell-free lifestyle supernatant in Dulbecco modified Eagle moderate) had been individually injected into two naive purpose-bred monkeys. Rabbit Polyclonal to UBAP2L. An intravenous infections at a higher dose was completed to be able to exclude artifacts because of limiting circumstances of infections. The pets were older (400 to 500 g) and in great physical health. Pets R207 and R217 received wild-type pathogen B222 and B240 got mutant 14-3.11 and B225 and R222 got mutant 14-4.6. ...

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Kryoglobuline sind Immunglobuline, die bei Temperaturen unter 37°C präzipitieren. Klinisch manifestiert sich eine Kryoglobulinämie mit sehr unterschiedlichen Symptomen an diversen Organen. Die klinisc

Aufgrund zahlreicher Charakteristika ist die Behandlung des älteren Patienten eine Herausforderung. Zunächst muss die Definition des älteren

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TY - JOUR. T1 - Sustained transcription of the immediate early gene arc in the dentate gyrus after spatial exploration. AU - Ramirez-Amaya, Victor. AU - Angulo-Perkins, Arafat. AU - Chawla, Monica K.. AU - Barnes, Carol A.. AU - Rosi, Susanna. PY - 2013/1/23. Y1 - 2013/1/23. N2 - After spatial exploration in rats, Arc mRNA is expressed in~2% of dentate gyrus (DG) granule cells, and this proportion of Arc-positive neurons remains stable for ~8 h. This long-term presence of Arc mRNA following behavior is not observed in hippocampal CA1 pyramidal cells. We report here that in rats~50% of granule cells with cytoplasmic Arc mRNA, induced some hours previously during exploration, also show Arc expression in the nucleus. This suggests that recent transcription can occur long after the exploration behavior that elicited it. To confirm that the delayed nuclear Arc expression was indeed recent transcription, Actinomycin D was administered immediately after exploration. This treatment resulted in ...

Cell. 1993 Nov 5;75(3):487-93. Research Support, Non-U.S. Govt; Research Support, U.S. Govt, Non-P.H.S.; Research Support, U.S. Govt, P.H.S.

The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing ...

Wright, Edward, Bain, Mark, Teague, Linda, Murphy, Jane and Sinclair, John (2005) Ets-2 repressor factor recruits histone deacetylase to silence human cytomegalovirus immediate-early gene expression in non-permissive cells. Journal of General Virology, 86 (3). pp. 535-544. ISSN 0022-1317 ...

The novelty of these results is twofold. One, increasingly, data that make the beneficial effects of C-peptide replenishment in type 1 diabetes irrefutable are accumulating (36). C-peptide exerts a beneficial effect on impaired nerve fiber regeneration in type 1 diabetes by normalizing early gene responses and expression of neurotrophic factors (33,37). It normalizes early metabolic abnormalities such as neural Na+/K+-ATPase activity and endoneurial endothelial nitric oxide synthase and corrects endoneurial blood flow (38-41), which underlie the early reversible metabolic nerve conduction defect (7). However, it does not affect oxidative stress in peripheral nerve (39). Two, here we demonstrate for the first time that the progressive nodal and paranodal structural changes, characteristic of both human and murine type 1 DPN (4,6,7), correlate with progressive decreases in the expression of the principal nodal and paranodal molecules and that these are correctable by C-peptide. The progressive ...

In the articles Central and Medial Amygdaloid Brain-Derived Neurotrophic Factor Signaling Plays a Critical Role in Alcohol-Drinking and Anxiety-Like Behaviors by Subhash C. Pandey, Huaibo Zhang, Adip Roy, and Kaushik Misra, which appeared on pages 8320-8331 of the August 9, 2006 issue, and Effector Immediate-Early Gene Arc in the Amygdala Plays a Critical Role in Alcoholism by Subhash C. Pandey, Huaibo Zhang, Rajesh Ugale, Anand Prakash, Tiejun Xu, and Kaushik Misra, which appeared on pages 2589-2600 of the March 5, 2008 issue, errors were made in figures. In Figure 5A of Pandey et al. (2006), the same photomicrograph was presented to document the placement of cannulae in aCSF- and BDNF antisense-treated subjects. In Figure 5B of Pandey et al. (2008), offset versions of the same photomicrograph were presented to document pCREB immunolabeling for the C+aCSF and C+BDNF treatments. In Figure 6B of Pandey et al. (2008), the same photomicrograph was presented to document Arc mRNA-positive cells ...

The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested ...

1. J.M. Schober, N. Chen, T.M. Greszkiewicz, I. Jovanovic, E.E. Emeson, T.P. Ugarova, R.D. Ye, L.F. Lau, S.C.-T. Lam. Identification of Integrin aMb2 as an Adhesion Receptor on Peripheral Blood Monocytes for Cyr61 (CCN1) and Connective Tissue Growth Factor (CCN2): Immediate-early Gene Products Expressed in Atherosclerotic Lesions. Blood. 2002;99:4457-4465. Pubmed ...

Alfonso-Dunn R, Turner A-MW, Beltran PMJean, Arbuckle JH, Budayeva HG, Cristea IM, et al. Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency. Cell Host Microbe. 2017 ;21(4):507-517.e5. ...

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