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https://www.readbyqxmd.com/read/27910923/protein-expression-from-unintegrated-hiv-1-dna-introduces-bias-in-primary-in-vitro-post-integration-latency-models
#1
Pawel Bonczkowski, Marie-Angélique De Scheerder, Eva Malatinkova, Alexandra Borch, Zora Melkova, Renate Koenig, Ward De Spiegelaere, Linos Vandekerckhove
To understand the persistence of latently HIV-1 infected cells in virally suppressed infected patients, a number of in vitro models of HIV latency have been developed. In an attempt to mimic the in vivo situation as closely as possible, several models use primary cells and replication-competent viruses in combination with antiretroviral compounds to prevent ongoing replication. Latency is subsequently measured by HIV RNA and/or protein production after cellular activation. To discriminate between pre- and post-integration latency, integrase inhibitors are routinely used, preventing novel integrations upon cellular activation...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905556/cellular-aspartyl-proteases-promote-the-unconventional-secretion-of-biologically-active-hiv-1-matrix-protein-p17
#2
Francesca Caccuri, Maria Luisa Iaria, Federica Campilongo, Kristen Varney, Alessandro Rossi, Stefania Mitola, Silvia Schiarea, Antonella Bugatti, Pietro Mazzuca, Cinzia Giagulli, Simona Fiorentini, Wuyuan Lu, Mario Salmona, Arnaldo Caruso
The human immune deficiency virus type 1 (HIV-1) matrix protein p17 (p17), although devoid of a signal sequence, is released by infected cells and detected in blood and in different organs and tissues even in HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, p17 deregulates the function of different cells involved in AIDS pathogenesis. The mechanism of p17 secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that HIV-1-infected cells can produce Gag without spreading infection in a model of viral latency...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27898737/transcriptomic-analysis-implicates-the-p53-signaling-pathway-in-the-establishment-of-hiv-1-latency-in-central-memory-cd4-t-cells-in-an-in-vitro-model
#3
Cory H White, Bastiaan Moesker, Nadejda Beliakova-Bethell, Laura J Martins, Celsa A Spina, David M Margolis, Douglas D Richman, Vicente Planelles, Alberto Bosque, Christopher H Woelk
The search for an HIV-1 cure has been greatly hindered by the presence of a viral reservoir that persists despite antiretroviral therapy (ART). Studies of HIV-1 latency in vivo are also complicated by the low proportion of latently infected cells in HIV-1 infected individuals. A number of models of HIV-1 latency have been developed to examine the signaling pathways and viral determinants of latency and reactivation. A primary cell model of HIV-1 latency, which incorporates the generation of primary central memory CD4 T cells (TCM), full-length virus infection (HIVNL4-3) and ART to suppress virus replication, was used to investigate the establishment of HIV latency using RNA-Seq...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27898590/reactivation-of-simian-immunodeficiency-virus-reservoirs-in-the-brain-of-virally-suppressed-macaques
#4
Lucio Gama, Celina M Abreu, Erin N Shirk, Sarah L Price, Ming Li, Greg M Laird, Kelly A Metcalf Pate, Stephen W Wietgrefe, Shelby L O'Connor, Luiz Pianowski, Ashley T Haase, Carine Van Lint, Robert F Siliciano, Janice E Clements
OBJECTIVE: Resting CD4 T cells have been recognized as the major cell reservoir of latent HIV-1 during antiretroviral therapy (ART). Using an simian immunodeficiency virus (SIV)/macaque model for AIDS and HIV-related neurocognitive disorders we assessed the contribution of the brain to viral latency and reactivation. DESIGN: Pigtailed macaques were dual inoculated with SIVDeltaB670 and SIV17E-Fr and treated with an efficacious central nervous system-penetrant ART...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27890943/recapitulation-of-acquired-immuno-deficiency-syndrome-associated-kaposi-s-sarcoma
#5
REVIEW
Balaji Govindan
Acquired immuno deficiency syndrome (AIDS) associated Kaposi's sarcoma (KS) is one of the clinical forms of KS. KS is caused by human herpes viruses 8 or KS associated herpes virus (KSHV). In India, till now, only 16 cases of AIDS associated KS was reported. Of all the clinical forms of KS, AIDS associated KS is distinct in many ways viz.; cutaneous manifestations commonly affects face and trunk rather than lower limbs, more mucosal lesions, rapidly progressive, and early systemic involvement. When human immunodeficiency virus (HIV) is co-infected with KSHV, in addition to the other pathogenic factors for the development of KS, HIV Tat protein promotes the proliferation of cytokine-activated endothelial cells and stimulates KS...
July 2016: Indian Journal of Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/27889530/identification-of-proximal-biomarkers-of-pkc-agonism-and-evaluation-of-their-role-in-hiv-reactivation
#6
Sai Vikram Vemula, Jill W Maxwell, Alexey Nefedov, Bang-Lin Wan, Justin Steve, William Newhard, Rosa I Sanchez, David Tellers, Richard J Barnard, Wade Blair, Daria Hazuda, Andrea L Webber, Bonnie J Howell
DESIGN: The HIV latent CD4(+) T cell reservoir is broadly recognized as a barrier to HIV cure. Induction of HIV expression using protein kinase C (PKC) agonists is one approach under investigation for reactivation of latently infected CD4(+) T cells (Beans et al., 2013; Abreu et al., 2014; Jiang et al., 2014; Jiang and Dandekar, 2015). We proposed that an increased understanding of the molecular mechanisms of action of PKC agonists was necessary to inform on biological signaling and pharmacodynamic biomarkers...
November 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27870832/position-effects-influence-hiv-latency-reversal
#7
Heng-Chang Chen, Javier P Martinez, Eduard Zorita, Andreas Meyerhans, Guillaume J Filion
The main obstacle to curing HIV is the presence of latent proviruses in the bodies of infected patients. The partial success of reactivation therapies suggests that the genomic context of integrated proviruses can interfere with treatment. Here we developed a method called Barcoded HIV ensembles (B-HIVE) to map the chromosomal locations of thousands of individual proviruses while tracking their transcriptional activities in an infected cell population. B-HIVE revealed that, in Jurkat cells, the expression of HIV is strongest close to endogenous enhancers...
November 21, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27869733/antiviral-therapy-by-hiv-1-broadly-neutralizing-and-inhibitory-antibodies
#8
REVIEW
Zhiqing Zhang, Shaowei Li, Ying Gu, Ningshao Xia
Human immunodeficiency virus type 1 (HIV-1) infection causes acquired immune deficiency syndrome (AIDS), a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART) but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1...
November 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27868442/-hiv-aids-and-law-in-hungary
#9
Máté Julesz
INTRODUCTION: The legal aspects of HIV/AIDS are mirrored by the statistical data. AIM: The aim of the author is to show the effect of HIV/AIDS on today's Hungarian society. METHOD: Analysis of data issued by the National Center for Epidemiology in Hungary and those to be found in the professional literature, as well as analysis of the Hungarian legal practice. RESULTS: Hungarian courts tend to impose a lighter punishment on a perpetrator diagnosed with AIDS than on a healthy perpetrator...
November 2016: Orvosi Hetilap
https://www.readbyqxmd.com/read/27837106/cutting-edge-t-regulatory-cell-depletion-reactivates-latent-simian-immunodeficiency-virus-siv-in-controller-macaques-while-boosting-siv-specific-t-lymphocytes
#10
Tianyu He, Egidio Brocca-Cofano, Benjamin B Policicchio, Ranjit Sivanandham, Rajeev Gautam, Kevin D Raehtz, Cuiling Xu, Ivona Pandrea, Cristian Apetrei
T regulatory cells (Tregs) are critical in shaping the latent HIV/SIV reservoir, as they are preferentially infected, reverse CD4(+) T cell activation status, and suppress CTL responses. To reactivate latent virus and boost cell-mediated immune responses, we performed in vivo Treg depletion with Ontak (denileukin diftitox) in two SIVsab-infected controller macaques. Ontak induced significant (>75%) Treg depletion and major CD4(+) T cell activation, and only minimally depleted CD8(+) T cells. The overall ability of Tregs to control immune responses was significantly impaired despite their incomplete depletion, resulting in both reactivation of latent virus (virus rebound to 10(3) viral RNA copies/ml plasma in the absence of antiretroviral therapy) and a significant boost of SIV-specific CD8(+) T cell frequency, with rapid clearance of reactivated virus...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27799305/heat-shock-protein-90-facilitates-latent-hiv-reactivation-through-maintaining-the-function-of-positive-transcriptional-elongation-factor-b-p-tefb-under-proteasome-inhibition
#11
Xiao-Yan Pan, Wei Zhao, Chun-Yan Wang, Jian Lin, Xiao-Yun Zeng, Ru-Xia Ren, Keng Wang, Tian-Rong Xun, Yechiel Shai, Shu-Wen Liu
The persistence of HIV in resting memory CD4+ T cells at a latent state is considered as the major barrier on the path to achieve a cure for HIV. Proteasome inhibitors (PIs) were previously reported as latency reversing agents (LRAs) but the mechanism underlying this function is yet unclear. Here we demonstrate that PIs reactivate latent HIV ex vivo without global T cell activation, and may facilitate host innate immune responses. Mechanistically, latent HIV reactivation induced by PIs is mediated by heat shock factor 1 (HSF1) via the recruitment of the heat shock protein (HSP) 90-positive transcriptional elongation factor b (p-TEFb) complex...
October 31, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27799218/tlr7-agonist-gs-9620-is-a-potent-inhibitor-of-acute-hiv-1-infection-in-human-peripheral-blood-mononuclear-cells
#12
Rujuta A Bam, Derek Hansen, Alivelu Irrinki, Andrew Mulato, Gregg S Jones, Joseph Hesselgesser, Christian R Frey, Tomas Cihlar, Stephen R Yant
GS-9620 is a potent and selective oral Toll-like receptor 7 (TLR7) agonist that directly activates plasmacytoid dendritic cells (pDCs). GS-9620 suppressed hepatitis B virus (HBV) in animal models of chronic infection and transiently activated HIV expression ex vivo in latently-infected peripheral blood mononuclear cells (PBMCs) from virally suppressed patients. Currently, GS-9620 is under clinical evaluation for treating chronic HBV infection and for reducing latent reservoirs in virally-suppressed HIV-infected patients...
October 31, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27795436/naf1-regulates-hiv-1-latency-by-suppressing-viral-promoter-driven-gene-expression-in-primary-cd4-t-cells
#13
Chuan Li, Hai-Bo Wang, Wen-Dong Kuang, Xiao-Xin Ren, Shu-Ting Song, Huan-Zhang Zhu, Qiang Li, Li-Ran Xu, Hui-Jun Guo, Li Wu, Jian-Hua Wang
: HIV-1 latency is characterized by reversible silencing of viral transcription driven by the long terminal repeat (LTR) promoter of HIV-1. Cellular and viral factors regulating the LTR activity contribute to HIV-1 latency and certain repressive cellular factors modulate viral transcription silencing. Nef-associated factor 1 (Naf1) is a host nucleo-cytoplasmic shuttling protein and regulates multiple cellular signal pathways and HIV-1 production. We have recently reported that the nucleus-located Naf1 promoted nuclear export of unspliced HIV-1 gag mRNA, leading to the accumulated Gag production...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27795414/identification-of-novel-kshv-orf50-transcripts-discovery-of-new-rta-isoforms-with-variable-transactivation-potential
#14
Brian S Wakeman, Yoshihiro Izumiya, Samuel H Speck
: Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been associated with primary effusion lymphoma, multicentric Castleman's disease, as well as its namesake Kaposi's sarcoma. As a gammaherpesvirus, KSHV is able to acutely replicate, enter latency, and reactivate from this latent state. A key protein involved in both acute replication and reactivation from latency is the replication and transcriptional activator (RTA) encoded by the gene Orf50. RTA is a known transactivator of multiple viral genes allowing for it to control the switch between latency and virus replication...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27781104/quantifying-integrated-siv-dna-by-repetitive-sampling-alu-gag-pcr
#15
EDITORIAL
Maud Mavigner, S Thera Lee, Jakob Habib, Cameron Robinson, Guido Silvestri, Una O'Doherty, Ann Chahroudi
OBJECTIVES: Although antiretroviral therapy (ART) effectively suppresses HIV-1 replication, it does not eradicate the virus and ART interruption consistently results in rebound of viraemia, demonstrating the persistence of a long-lived viral reservoir. Several approaches aimed at reducing virus persistence are being developed, and accurate measurements of the latent reservoir (LR) are necessary to assess the effectiveness of anti-latency interventions. We sought to measure the LR in SIV/SHIV-infected rhesus macaques (RMs) by quantifying integrated SIV-DNA...
October 5, 2016: Journal of Virus Eradication
https://www.readbyqxmd.com/read/27780916/efficient-generation-of-antigen-specific-ctls-by-the-baff-activated-human-b-lymphocytes-as-apcs-a-novel-approach-for-immunotherapy
#16
Zhang Yiwen, Gao Shilin, Chen Yingshi, Su Lishi, Luo Baohong, Liu Chao, Li Linghua, Pan Ting, Zhang Hui
Efficient antigen presentation is indispensable for cytotoxic T lymphocyte (CTL)-mediated immunotherapy. B-lymphocytes propagated with CD40L have been developed as antigen-presenting cells (APCs), but this capacity needs further optimization. Here, we aimed to expand human B-lymphocytes on a large scale while maintaining their antigen-presenting ability by using both CD40L and B-cell activating factor (BAFF). The addition of BAFF enhanced the expansion efficiency and prolonged the culture time without causing apoptosis of the expanded B-cells...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27777245/subacute-sclerosing-panencephalitis-in-a-child-with-hiv-co-infection
#17
Pradeep Kumar Maurya, Mayur Deepak Thakkar, Dinkar Kulshreshtha, Ajai Kumar Singh, Anup Kumar Thacker
Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. The effect of human immunodeficiency virus (HIV) co-infection on subacute sclerosing panencephalitis remains elusive and rare. We report a child who developed subacute sclerosing panencephalitis following a short latency period and a rapidly progressive course with HIV co-infection.
October 24, 2016: Clinical Medicine & Research
https://www.readbyqxmd.com/read/27769267/activation-of-hiv-1-expression-in-latently-infected-cd4-t-cells-by-the-small-molecule-pkc412
#18
Zhujun Ao, Rong Zhu, Xiaoli Tan, Lisa Liu, Liyu Chen, Shuiping Liu, XiaoJian Yao
BACKGROUND: HIV-1 latency is a major obstacle for HIV-1 eradication. Extensive efforts are being directed toward the reactivation of latent HIV reservoirs with the aim of eliminating latently infected cells via the host immune system and/or virus-mediated cell lysis. RESULTS: We screened over 1,500 small molecules and kinase inhibitors and found that a small molecule, PKC412 (midostaurin, a broad-spectrum kinase inhibitor), can stimulate viral transcription and expression from the HIV-1 latently infected ACH2 cell line and primary resting CD4+ T cells...
October 21, 2016: Virology Journal
https://www.readbyqxmd.com/read/27768313/sesterterpenoids-isolated-from-the-sponge-phorbas-sp-activate-latent-hiv-1-provirus-expression
#19
Meng Wang, Ian Tietjen, Min Chen, David E Williams, Julie Daoust, Mark A Brockman, Raymond J Andersen
Eight new sesterterpenoids, alotaketals D (8) and E (9), ansellones D (10), E (11), F (12), and G (13), anvilones A (14), and B (15), have been isolated from extracts of the marine sponge Phorbas sp. collected in Howe Sound British Columbia and their structures have been elucidated by analysis of NMR and MS data. Ansellone F (12) contains a rare 1,2-3,4 bis epoxy decalin substructure. Anvilones A (14) and B (15) have the unprecedented tetracylic anvilane terpenoid carbon skeleton. Using a cell culture model of latent HIV-1 infection, ansellone A (3), alotaketal D (8), and anvilone A (14) were found to induce HIV proviral gene expression similar to a control compound prostratin (1), while the known sesterterpenoid alotaketal C (2), isolated from the same extract, was more potent and gave a stronger response than prostratin (1)...
October 21, 2016: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/27761954/novel-insights-into-role-of-mir-320a-vdac1-axis-in-astrocyte-mediated-neuronal-damage-in-neuroaids
#20
Mahar Fatima, Bharat Prajapati, Kanza Saleem, Rina Kumari, Chitra Mohindar Singh Singal, Pankaj Seth
Astroglia are indispensable component of the tripartite synapse ensheathing innumerous soma and synapses. Its proximity to neurons aids the regulation of neuronal functions, health and survival through dynamic neuroglia crosstalk. Susceptibility of astrocyte to HIV-1 infection and subsequent latency culminates in compromised neuronal health. The viral protein HIV-1 transactivator of transcription (Tat) is neurotoxic. HIV-1 Tat is detected in brain of AIDS patients even in cases where viral load is non-detectable due to successful HAART therapy...
October 20, 2016: Glia
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