Genomes and Genes
Summary: The ability of a pathogenic virus to lie dormant within a cell (latent infection). In eukaryotes, subsequent activation and viral replication is thought to be caused by extracellular stimulation of cellular transcription factors. Latency in bacteriophage is maintained by the expression of virally encoded repressors.
- Azarkh Y, Bos N, Gilden D, Cohrs R. Human trigeminal ganglionic explants as a model to study alphaherpesvirus reactivation. J Neurovirol. 2012;18:456-61 pubmed publisher..Investigations of VZV latency and reactivation have been hindered by the lack of an in vitro model of virus latency. Since VZV is an exclusively human pathogen, we used naturally infected human trigeminal ganglia (TG) obtained ..
- Boehm D, Calvanese V, Dar R, Xing S, Schroeder S, Martins L, et al. BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism. Cell Cycle. 2013;12:452-62 pubmed publisher..Collectively, our results identify BRD2 as a new Tat-independent suppressor of HIV transcription in latently infected cells and underscore the therapeutic potential of BET inhibitors in the reversal of HIV latency. ..
- Jong J, Cha S, Jang J, Seo T. Alteration of histone H3 lysine 4 trimethylation on putative lytic gene promoters by human Set1 complex during reactivation of Kaposi's sarcoma-associated herpesvirus. Intervirology. 2013;56:91-103 pubmed publisher..These results demonstrate that the increase of H3K4me3 by human Set1 complex is involved in activation of lytic genes during the lytic infection of KSHV. ..
- Banerjee C, Archin N, Michaels D, Belkina A, Denis G, Bradner J, et al. BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J Leukoc Biol. 2012;92:1147-54 pubmed publisher..Thus, JQ1 may be useful in studies of potentially novel mechanisms for transcriptional control as well as in translational efforts to identify therapeutic molecules to achieve viral eradication. ..
- Sloutskin A, Kinchington P, Goldstein R. Productive vs non-productive infection by cell-free varicella zoster virus of human neurons derived from embryonic stem cells is dependent upon infectious viral dose. Virology. 2013;443:285-93 pubmed publisher..These results further validate the use of this unlimited source of human neurons for studying unexplored aspects of VZV interaction with neurons such as entry, latency and reactivation. ..
- Dahabieh M, Ooms M, Simon V, Sadowski I. A doubly fluorescent HIV-1 reporter shows that the majority of integrated HIV-1 is latent shortly after infection. J Virol. 2013;87:4716-27 pubmed publisher..Taken together, our data, generated using the newly developed RGH vector as a sensitive tool to analyze HIV-1 latency on a single-cell level, show that the majority of HIV-1 infections are latent early postinfection...
- Weekes M, Tan S, Poole E, Talbot S, Antrobus R, Smith D, et al. Latency-associated degradation of the MRP1 drug transporter during latent human cytomegalovirus infection. Science. 2013;340:199-202 pubmed publisher..The UL138-mediated loss of MRP1 provides a marker for detecting latent HCMV infection and a therapeutic target for eliminating latently infected cells before transplantation. ..
- Chang H, Ganem D. A unique herpesviral transcriptional program in KSHV-infected lymphatic endothelial cells leads to mTORC1 activation and rapamycin sensitivity. Cell Host Microbe. 2013;13:429-40 pubmed publisher..These studies reveal the existence of a unique herpesviral gene expression program corresponding to neither canonical latency nor lytic replication, with important pathogenetic and therapeutic consequences. ..
- Tyagi M, Bukrinsky M. Human immunodeficiency virus (HIV) latency: the major hurdle in HIV eradication. Mol Med. 2012;18:1096-108 pubmed publisher..We will describe the hurdles being faced in eradicating latent HIV proviruses. We will also briefly discuss the ongoing strategies aimed toward curing HIV infection. ..
- Ho Y, Shan L, Hosmane N, Wang J, Laskey S, Rosenbloom D, et al. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell. 2013;155:540-51 pubmed publisher..The identification of replication-competent noninduced proviruses indicates that the size of the latent reservoir-and, hence, the barrier to cure-may be up to 60-fold greater than previously estimated...
- Darst R, Haecker I, Pardo C, Renne R, Kladde M. Epigenetic diversity of Kaposi's sarcoma-associated herpesvirus. Nucleic Acids Res. 2013;41:2993-3009 pubmed publisher..Our findings show that epigenetic drift can restrict viral propagation by chromatin compaction at latent and lytic promoters. ..
- Poole E, Walther A, Raven K, BENEDICT C, Mason G, Sinclair J. The myeloid transcription factor GATA-2 regulates the viral UL144 gene during human cytomegalovirus latency in an isolate-specific manner. J Virol. 2013;87:4261-71 pubmed publisher..Taken together, these data suggest that the HCMV latency-associated transcriptome may be virus isolate specific and dependent on the repertoire of transcription factor binding sites in the promoters of latency-associated genes. ..
- Roesch F, Meziane O, Kula A, Nisole S, Porrot F, Anderson I, et al. Hyperthermia stimulates HIV-1 replication. PLoS Pathog. 2012;8:e1002792 pubmed publisher..Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity. ..
- Wilson A, Mohr I. A cultured affair: HSV latency and reactivation in neurons. Trends Microbiol. 2012;20:604-11 pubmed publisher..With this comes a growing appreciation for how the life cycles of HSV-1 and other herpesviruses are governed by key host pathways controlling metabolic homeostasis and cell identity. ..
- Habison A, Beauchemin C, Simas J, Usherwood E, Kaye K. Murine gammaherpesvirus 68 LANA acts on terminal repeat DNA to mediate episome persistence. J Virol. 2012;86:11863-76 pubmed publisher..Similar to KSHV LANA, mLANA broadly associated with mitotic chromosomes but relocalized to concentrated dots in the presence of episomes. Therefore, mLANA acts on mTR elements to mediate MHV68 episome persistence. ..
- Eisele E, Siliciano R. Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity. 2012;37:377-88 pubmed publisher..Further research is urgently required on potential reservoirs in the gut-associated lymphoid tissue and the central nervous system. ..
- Blazkova J, Chun T, Belay B, Murray D, Justement J, Funk E, et al. Effect of histone deacetylase inhibitors on HIV production in latently infected, resting CD4(+) T cells from infected individuals receiving effective antiretroviral therapy. J Infect Dis. 2012;206:765-9 pubmed publisher..Here we demonstrate that HDACis do not induce HIV production in the latent viral reservoir of aviremic individuals. Therefore, alternative therapeutic strategies may be necessary to eliminate HIV in the latent viral reservoir. ..
- Fernandez G, Zaikos T, Khan S, Jacobi A, Behlke M, Zeichner S. Targeting I?B proteins for HIV latency activation: the role of individual I?B and NF-?B proteins. J Virol. 2013;87:3966-78 pubmed publisher..I?B? knockdown may offer attractive therapeutic advantages for HIV activation because it is not essential for mammalian growth and development and because new siRNA delivery strategies may target siRNAs to HIV latently infected cells. ..
- Duverger A, Wolschendorf F, Zhang M, Wagner F, Hatcher B, Jones J, et al. An AP-1 binding site in the enhancer/core element of the HIV-1 promoter controls the ability of HIV-1 to establish latent infection. J Virol. 2013;87:2264-77 pubmed publisher..Given that these minimal changes in a transcription factor binding site affect latency establishment to such large extent, our data support the notion that HIV-1 latency is a transcription factor restriction phenomenon. ..
- McDonnel S, Sparger E, Luciw P, Murphy B. Transcriptional regulation of latent feline immunodeficiency virus in peripheral CD4+ T-lymphocytes. Viruses. 2012;4:878-88 pubmed publisher..Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus...
- Doyon G, Zerbato J, Mellors J, Sluis Cremer N. Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog. AIDS. 2013;27:F7-F11 pubmed publisher..for the treatment of alcoholism, was shown to reactivate latent HIV-1 expression in a primary cell model of virus latency and is currently being assessed in a clinical trial for its potential to deplete the latent HIV-1 reservoir in ..
- Chen H, Wikramasinghe P, Showe L, Lieberman P. Cohesins repress Kaposi's sarcoma-associated herpesvirus immediate early gene transcription during latency. J Virol. 2012;86:9454-64 pubmed publisher..Our findings implicate cohesins as a major repressor of KSHV lytic gene activation and show that they function coordinately with CTCF to regulate the switch between latent and lytic gene activity. ..
- Donahue D, Wainberg M. Cellular and molecular mechanisms involved in the establishment of HIV-1 latency. Retrovirology. 2013;10:11 pubmed publisher..We also discuss the role of immediate silent integration of viral DNA versus silencing of initially active infections. Finally, we discuss potential approaches aimed at limiting the establishment of latent infection. ..
- Grigoryan S, Kinchington P, Yang I, Selariu A, Zhu H, Yee M, et al. Retrograde axonal transport of VZV: kinetic studies in hESC-derived neurons. J Neurovirol. 2012;18:462-70 pubmed publisher..hESC-derived neurons are, therefore, a powerful model for studying axonal transport of VZV and molecular characteristics of neuronal infection. ..
- Kobayashi M, Wilson A, Chao M, Mohr I. Control of viral latency in neurons by axonal mTOR signaling and the 4E-BP translation repressor. Genes Dev. 2012;26:1527-32 pubmed publisher..Finally, inhibiting mTOR in axons induced reactivation. Thus, local changes in axonal mTOR signaling that control translation regulate latent HSV1 genomes in a spatially segregated compartment...
- Pace M, Graf E, Agosto L, Mexas A, Male F, Brady T, et al. Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency. PLoS Pathog. 2012;8:e1002818 pubmed publisher..These results have implications for therapies targeting the latent reservoir and suggest that some latent cells could be cleared by a robust immune response. ..
- Webre J, Hill J, Nolan N, Clement C, McFerrin H, Bhattacharjee P, et al. Rabbit and mouse models of HSV-1 latency, reactivation, and recurrent eye diseases. J Biomed Biotechnol. 2012;2012:612316 pubmed publisher..This paper is pertinent but not intended to be all inclusive. We will give examples of key papers that have reported novel discoveries related to the review topics. ..
- Ouwendijk W, Abendroth A, Traina Dorge V, Getu S, Steain M, Wellish M, et al. T-cell infiltration correlates with CXCL10 expression in ganglia of cynomolgus macaques with reactivated simian varicella virus. J Virol. 2013;87:2979-82 pubmed publisher..CXCL10 RNA colocalized with T-cell clusters. After SVV reactivation, transient T-cell infiltration, possibly mediated by CXCL10, parallels varicella zoster virus (VZV) reactivation in humans. ..
- Shirakawa K, Chavez L, Hakre S, Calvanese V, Verdin E. Reactivation of latent HIV by histone deacetylase inhibitors. Trends Microbiol. 2013;21:277-85 pubmed publisher..Here, we review the basic biology of HDACs and their inhibitors, the role of HDACs in HIV latency, and recent efforts to use HDAC inhibitors to reactivate latent HIV in vitro and in vivo. ..
- Ying H, Zhang Y, Zhou X, Qu X, Wang P, Liu S, et al. Selective histonedeacetylase inhibitor M344 intervenes in HIV-1 latency through increasing histone acetylation and activation of NF-kappaB. PLoS ONE. 2012;7:e48832 pubmed publisher..These results suggest the potential of M344 in anti-latency therapies and an important role for histone modifications and NF-ÎºB transcription factors in regulating HIV-1 LTR gene expression. ..
- Evans V, Khoury G, Saleh S, Cameron P, Lewin S. HIV persistence: chemokines and their signalling pathways. Cytokine Growth Factor Rev. 2012;23:151-7 pubmed publisher..Here we review the role of chemokines in HIV persistence; the main signalling pathways that are involved; and how these pathways may be exploited to develop novel strategies to reduce or eliminate latently infected cells. ..
- Murphy B, Hillman C, Mok M, Vapniarsky N. Lentiviral latency in peripheral CD4+ T cells isolated from feline immunodeficiency virus-infected cats during the asymptomatic phase is not associated with hypermethylation of the proviral promoter. Virus Res. 2012;169:117-26 pubmed publisher..Here we report no evidence that proviral promoter hypermethylation is associated with lentiviral latency in peripheral CD4+ T cells and monocytes obtained from experimentally FIV-infected cats. ..
- Yu X, Seitz S, Pointon T, Bowlin J, Cohrs R, Jonjic S, et al. Varicella zoster virus infection of highly pure terminally differentiated human neurons. J Neurovirol. 2013;19:75-81 pubmed publisher..VZV infection of highly pure terminally differentiated human neurons provides a unique in vitro system to study the VZV-neuronal relationship and the potential to investigate mechanisms of VZV reactivation...
- Toth Z, Brulois K, Wong L, Lee H, Chung B, Jung J. Negative elongation factor-mediated suppression of RNA polymerase II elongation of Kaposi's sarcoma-associated herpesvirus lytic gene expression. J Virol. 2012;86:9696-707 pubmed publisher..These results indicate that the transcription elongation of KSHV OriLytL-K7 lytic genes is inhibited by NELF during latency, but can also be promptly reactivated in an RTA-independent manner upon external stimuli. ..
- Lusic M, Marini B, Ali H, Lucic B, Luzzati R, Giacca M. Proximity to PML nuclear bodies regulates HIV-1 latency in CD4+ T cells. Cell Host Microbe. 2013;13:665-77 pubmed publisher..Thus, nuclear topology and active gene movement mediate HIV-1 transcriptional regulation and have implications for controlling HIV-1 latency and eradication...
- Smith G. Herpesvirus transport to the nervous system and back again. Annu Rev Microbiol. 2012;66:153-76 pubmed publisher..This remarkable cycle of infection is the topic of this review. In addition, some of the distinguishing hallmarks of the infections caused by these viruses are evaluated in terms of their underlying similarities...
- Heuts F, Rottenberg M, Salamon D, Rasul E, Adori M, Klein G, et al. T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice. J Virol. 2014;88:3235-45 pubmed publisher..Our results indicate that CD4(+) T cells are responsible for the switch to a nonproliferating EBV program during primary infection with EBV. ..
- Xing S, Siliciano R. Targeting HIV latency: pharmacologic strategies toward eradication. Drug Discov Today. 2013;18:541-51 pubmed publisher..In this review, we discuss current pharmacological approaches toward eradication, focusing on small molecule latency-reversing agents, their mechanisms, advantages and limitations. ..
- Nicoll M, Proença J, Connor V, Efstathiou S. Influence of herpes simplex virus 1 latency-associated transcripts on the establishment and maintenance of latency in the ROSA26R reporter mouse model. J Virol. 2012;86:8848-58 pubmed publisher..We conclude that the HSV-1 LATs facilitate the long-term stability of the latent cell population within the infected host and that interpretation of LAT establishment phenotypes is influenced by infection methodology. ..
- Zhou G, Du T, Roizman B. HSV carrying WT REST establishes latency but reactivates only if the synthesis of REST is suppressed. Proc Natl Acad Sci U S A. 2013;110:E498-506 pubmed publisher..The results suggest that REST plays a transient role in the establishment of latency but not in reactivation and suggest the existence of at least two phases at both establishment and reactivation. ..
- Goodwin T, McCarthy M, Osterrieder N, Cohrs R, Kaufer B. Three-dimensional normal human neural progenitor tissue-like assemblies: a model of persistent varicella-zoster virus infection. PLoS Pathog. 2013;9:e1003512 pubmed publisher..Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells. ..