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https://www.readbyqxmd.com/read/29777875/switching-cell-penetrating-and-cxcr4-binding-activities-of-nanoscale-organized-arginine-rich-peptides
#1
Marianna Teixeira de Pinho Favaro, Naroa Serna, Laura Sánchez-García, Rafael Cubarsi, Mónica Roldán, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón Mangues, Neus Ferrer-Miralles, Adriano Rodrigues Azzoni, Esther Vázquez, Antonio Villaverde
Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown...
May 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29768164/epigenomic-guided-mass-cytometry-profiling-reveals-disease-specific-features-of-exhausted-cd8-t-cells
#2
Bertram Bengsch, Takuya Ohtani, Omar Khan, Manu Setty, Sasikanth Manne, Shaun O'Brien, Pier Federico Gherardini, Ramin Sedaghat Herati, Alexander C Huang, Kyong-Mi Chang, Evan W Newell, Niels Bovenschen, Dana Pe'er, Steven M Albelda, E John Wherry
Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29760177/epigenetic-promoter-dna-methylation-of-mir-124-promotes-hiv-1-tat-mediated-microglial-activation-via-mecp2-stat3-axis
#3
Palsamy Periyasamy, Annadurai Thangaraj, Ming-Lei Guo, Guoku Hu, Shannon Callen, Shilpa Buch
The present study demonstrates HIV-1 Tat-mediated epigenetic downregulation of microglial miR-124 and its association with microglial activation. Exposure of mouse primary microglia isolated from newborn pups of either sex to HIV-1 Tat resulted in decreased expression of primary miR-124-1, primary miR-124-2 as well as the mature miR-124. In parallel, HIV-1 Tat exposure to mouse primary microglial cells resulted in increased expression of DNA methylation enzymes, such as DNMT1, DNMT3A, and DNMT3B that were also accompanied by increased global DNA methylation...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29756454/discordance-in-drug-resistance-mutations-between-blood-plasma-and-semen-or-rectal-secretion-among-newly-diagnosed-hiv-1-infected-thai-msm
#4
Akarin Hiransuthikul, Rapeeporn Wongkanya, Sunee Sirivichayakul, Deondara Trachunthong, Thanthip Sungsing, Tippawan Pankam, Praphan Phanuphak, Nittaya Phanuphak
HIV-1 infection is most commonly transmitted by sexual contact across mucosal surfaces. Information on concordance in drug resistance profile between blood plasma and anogenital compartments in resource-limited settings is limited. We aimed to determine discordances in genotypic drug resistance-associated mutations (DRAMs) between blood plasma and semen or rectal secretions among newly diagnosed, antiretroviral therapy (ART)-naïve, HIV-1-infected Thai men who have sex with men (MSM). Blood plasma, semen, and rectal secretions of HIV-1-infected Thai MSM enrolled from the Test and Treat cohort were tested for genotypic mutations in the reverse transcriptase and protease genes...
May 14, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29755454/the-use-of-the-humanized-mouse-model-in-gene-therapy-and-immunotherapy-for-hiv-and-cancer
#5
REVIEW
Mayra A Carrillo, Anjie Zhen, Scott G Kitchen
HIV and cancer remain prevailing sources of morbidity and mortality worldwide. There are current efforts to discover novel therapeutic strategies for the treatment or cure of these diseases. Humanized mouse models provide the investigative tool to study the interaction between HIV or cancer and the human immune system in vivo . These humanized models consist of immunodeficient mice transplanted with human cells, tissues, or hematopoietic stem cells that result in reconstitution with a nearly full human immune system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29748498/single-viruses-on-the-fluorescence-microscope-imaging-molecular-mobility-interactions-and-structure-sheds-new-light-on-viral-replication
#6
REVIEW
Nagma Parveen, Doortje Borrenberghs, Susana Rocha, Jelle Hendrix
Viruses are simple agents exhibiting complex reproductive mechanisms. Decades of research have provided crucial basic insights, antiviral medication and moderately successful gene therapy trials. The most infectious viral particle is, however, not always the most abundant one in a population, questioning the utility of classic ensemble-averaging virology. Indeed, viral replication is often not particularly efficient, prone to errors or containing parallel routes. Here, we review different single-molecule sensitive fluorescence methods that we employ routinely to investigate viruses...
May 10, 2018: Viruses
https://www.readbyqxmd.com/read/29740045/exosome-markers-associated-with-immune-activation-and-oxidative-stress-in-hiv-patients-on-antiretroviral-therapy
#7
Sukrutha Chettimada, David R Lorenz, Vikas Misra, Simon T Dillon, R Keith Reeves, Cordelia Manickam, Susan Morgello, Gregory D Kirk, Shruti H Mehta, Dana Gabuzda
Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739342/high-prevalence-of-hiv-1-transmitted-drug-resistance-among-therapy-na%C3%A3-ve-burmese-entering-travelers-at-dehong-ports-in-yunnan-china
#8
Qicai Xuan, Shuwen Liang, Weihong Qin, Shuting Yang, A-Mei Zhang, Ting Zhao, Hui Su, Zhiqing Xia, Binghui Wang, Xueshan Xia
BACKGROUND: The overall success of Human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy (ART) was heavily challenged upon the occurrence of drug resistance. Dehong Prefecture witnessed not only the first report of HIV-1 infection but also the experimental adoption of antiviral treatment in China. The transmission and epidemic of HIV-1 in Dehong is impacted by cross-border activities. The characteristics of HIV-1 drug resistance among therapy-naïve Burmese entering travelers in Yunnan and their speculated origin are still not clarified...
May 8, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29737506/hiv-1-protein-tat-1-72-impairs-neuronal-dendrites-via-activation-of-pp1-and-regulation-of-the-creb-bdnf-pathway
#9
Yu Liu, Deyu Zhou, Jiabin Feng, Zhou Liu, Yue Hu, Chang Liu, Xiaohong Kong
Despite the success of combined antiretroviral therapy in recent years, the prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders in people living with HIV-1 is increasing, significantly reducing the health-related quality of their lives. Although neurons cannot be infected by HIV-1, shed viral proteins such as transactivator of transcription (Tat) can cause dendritic damage. However, the detailed molecular mechanism of Tat-induced neuronal impairment remains unknown. In this study, we first showed that recombinant Tat (1-72 aa) induced neurotoxicity in primary cultured mouse neurons...
May 8, 2018: Virologica Sinica
https://www.readbyqxmd.com/read/29734217/dysregulation-of-apoptosis-and-autophagy-gene-expression-in-pbmcs-of-efficiently-treated-hiv-infected-patients
#10
Amandine Serrano, Saïd El Haddad, Frédéric Moal, Thierry Prazuck, Eric Legac, Chloé Robin, Fabienne Brule, Stéphane Charpentier, Thierry Normand, Alain Legrand, Laurent Hocqueloux, Lucile Mollet
OBJECTIVE: We measure the transcript levels of the pro-apoptotic GALIG, anti-apoptotic MCL1 genes and those of the autophagy genes BECN1, MAP1LC3B, ATG9a, P62/SQSTM1, GABARAP, GABARAPL1 and GABARAPL2 to define if mRNA alteration can characterize HIV infected patients effectively treated with combined antiretroviral therapy (cART). DESIGN: Monocentric pilot study conducted on PBMC of 40 uninfected donors and 27 HIV positive patients effectively treated by cART for at least 8...
May 3, 2018: AIDS
https://www.readbyqxmd.com/read/29732988/appearance-of-drug-resistance-mutations-among-the-dominant-hiv-1-subtype-crf01_ae-in-maumere-indonesia
#11
Dwi Wahyu Indriati, Tomohiro Kotaki, Siti Qamariyah Khairunisa, Adiana Mutamsari Witaningrum, Muhammad Qushai Yunifiar Matondang, Shuhei Ueda, Nasronudin, Asep Purnama, Dwi Kurniawan, Masanori Kameoka
BACKGROUND AND OBJECTIVES: Human Immunodeficiency Virus (HIV) is still a major health issue in Indonesia. In recent years, the appearance of drug resistance-associated mutations has reduced the effectiveness of antiretroviral therapy (ART). We conducted genotypic studies, including the detection of drug resistance-associated mutations (from first-line regimen drugs), on HIV-1 genes derived from infected individuals in Maumere, West Nusa Tenggara. Maumere, a transit city in West Nusa Tenggara, which has a high HIV-1 transmission rate...
May 1, 2018: Current HIV Research
https://www.readbyqxmd.com/read/29732907/prevalence-of-rilpivirine-and-etravirine-resistance-mutations-in-hiv-1-subtype-c-infected-patients-failing-nevirapine-or-efavirenz-based-combination-antiretroviral-therapy-in-botswana
#12
Thabo Diphoko, Simani Gaseitsiwe, Ishmael Kasvosve, Sikhulile Moyo, Harriet Okatch, Rosemary Musonda, Mark A Wainberg, Joseph Makhema, Richard Marlink, Vladimir Novitsky, M Essex
BACKGROUND: Rilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1drug-resistance mutations (DRM) to RPV and ETR in Botswana. METHODS: A total of 168 HIV-1 polymerase gene sequences from participants failing nevirapine or efavirenz-containing regimens were analysed for drug resistance mutations using the Stanford University HIV drug resistance database...
May 6, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29732382/common-variation-in-nlrp3-is-associated-with-early-death-and-elevated-inflammasome-biomarkers-among-advanced-hiv-tb-co-infected-patients-in-botswana
#13
Shruthi Ravimohan, Kebatshabile Nfanyana, Neo Tamuhla, Caroline T Tiemessen, Drew Weissman, Gregory P Bisson
Background: Elevated inflammation is associated with early mortality among HIV/tuberculosis (TB) patients starting antiretroviral therapy (ART); however, the sources of immune activation are unclear. We hypothesized that common variation in innate immune genes contributes to excessive inflammation linked to death. As single nucleotide polymorphisms (SNPs) in inflammasome pathway genes can increase risk for inflammatory diseases, we investigated their association with early mortality among a previously described cohort of HIV/TB patients initiating ART in Botswana...
May 2018: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29731256/antiretroviral-therapy-potentiates-high-fat-diet-induced-obesity-and-glucose-intolerance
#14
Mark E Pepin, Lindsey E Padgett, Ruth E McDowell, Ashley R Burg, Manoja K Brahma, Cassie Holleman, Teayoun Kim, David Crossman, Olaf Kutsch, Hubert M Tse, Adam R Wende, Kirk M Habegger
OBJECTIVE: Breakthroughs in HIV treatment, especially combination antiretroviral therapy (ART), have massively reduced AIDS-associated mortality. However, ART administration amplifies the risk of non-AIDS defining illnesses including obesity, diabetes, and cardiovascular disease, collectively known as metabolic syndrome. Initial reports suggest that ART-associated risk of metabolic syndrome correlates with socioeconomic status, a multifaceted finding that encompasses income, race, education, and diet...
April 20, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29720521/short-term-pifn-%C3%AE-2a-treatment-does-not-significantly-reduce-the-viral-reservoir-of-siv-infected-art-treated-rhesus-macaques
#15
David Palesch, Steven E Bosinger, Maud Mavigner, James M Billingsley, Cameron Mattingly, Diane Carnathan, Mirko Paiardini, Ann Chahroudi, Thomas Vanderford, Guido Silvestri
The major obstacle to HIV-1 eradication is a reservoir of latently infected cells that persists despite long-term antiretroviral therapy (ART) and causes rapid viral rebound if treatment is interrupted. Type I interferons are immunomodulatory cytokines that induce antiviral factors and have been evaluated for the treatment of HIV-infected individuals, resulting in moderate reduction of viremia and inconclusive data about their effect on reservoir size. Here, we assessed the potential of pegylated IFN-α2a (pIFN-α2a) to reduce the viral reservoir in SIV-infected, ART-treated rhesus macaques (RMs)...
May 2, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29720516/seminal-siv-in-chronically-infected-cynomolgus-macaques-is-dominated-by-virus-originating-from-multiple-genital-organs
#16
Laurent Houzet, Marcos Pérez-Losada, Giulia Matusali, Claire Deleage, Nathalie Dereuddre-Bosquet, Anne-Pascale Satie, Florence Aubry, Emmanuelle Becker, Bernard Jégou, Roger Le Grand, Brandon F Keele, Keith A Crandall, Nathalie Dejucq-Rainsford
The sexual transmission of viruses is responsible for the spread of multiple infectious diseases. Although the HIV/AIDS pandemic remains fueled by sexual contacts with infected semen, the origin of virus in semen is still unknown. In a substantial number of HIV- infected men, viral strains present in semen differ from the ones in blood, suggesting that HIV is locally produced within the genital tract. Such local production may be responsible for the persistence of HIV in semen despite effective antiretroviral therapy...
May 2, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29705873/association-of-trimcyp-and-trim5%C3%AE-from-assam-macaques-leads-to-a-functional-trade-off-between-hiv-1-and-n-mlv-inhibition
#17
Dan Mu, Jia-Wu Zhu, Feng-Liang Liu, Hong-Yi Zheng, Yong-Tang Zheng
TRIM5α restricts retroviruses in a species-specific manner. Cyclophilin A was independently retrotransposed into the TRIM5 loci in different species, leading to the generation of antiviral TRIM5-cyclophilin A (TRIMCyp) proteins. Previously, we found that assam macaques express a TRIMCyp chimera (amTRIMCyp), along with a TRIM5α allelic protein (amTRIM5α). Herein, we investigated the antiviral activity of amTRIMCyp and amTRIM5α individually, as well as their interaction and joint effects. amTRIMCyp showed a divergent restriction pattern from amTRIM5α...
April 26, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29698467/hiv-1-genetic-transmission-networks-among-men-who-have-sex-with-men-in-kunming-china
#18
Min Chen, Yanling Ma, Huichao Chen, Jie Dai, Lijuan Dong, Chaojun Yang, Youfang Li, Hongbing Luo, Renzhong Zhang, Xiaomei Jin, Li Yang, Allen Ka Loon Cheung, Manhong Jia, Zhizhong Song
BACKGROUND: Yunnan has the greatest share of reported human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) cases in China. In recent years, HIV prevalence and incidence remained stubbornly high in men who have sex with men (MSM). To follow the dynamics of the HIV-1 epidemic among MSM, HIV-1 genetic characteristics and genetic transmission networks were investigated. METHODS: Blood samples from 190 newly diagnosed HIV-1 cases among MSM were continuously collected at fixed sites from January 2013 to December 2015 in Kunming City, Yunnan Province...
2018: PloS One
https://www.readbyqxmd.com/read/29695698/-protection-of-lymphocytes-against-hiv-using-lentivirus-vector-carrying-a-combination-of-trim5%C3%AE-hrh-genes-and-microrna-against-ccr5
#19
D O Omelchenko, D V Glazkova, E V Bogoslovskaya, F A Urusov, Y A Zhogina, G M Tsyganova, G A Shipulin
Gene therapy is considered a promising approach to treating infections caused by human immunodeficiency virus (HIV). One strategy is to introduce antiviral genes into cells in order to impart resistance to HIV. In this work, the antiviral activity of new anti-HIV lentiviral vector pT has been studied. The vector carries a combination that consists of two identical artificial miRNA mic13lg and the TRIM5α-HRH gene. Two mic13lg microRNAs suppress the expression of the CCR5 gene, which encodes the HIV coreceptor and, thus, prevents the penetration of R5-tropic HIV strains into the cell...
March 2018: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29689537/hiv-infection-advances-toward-a-cure
#20
Daniel C Douek
Achieving cure of HIV infection requires eliminating all replication-competent virus from the reservoir of latently infected cells or completely inhibiting infected cells from emerging from latency. Strategies include very early use of antiretroviral therapy; hematopoietic stem cell transplantation; "shock-and-kill" approaches; immune therapy with immune checkpoint inhibitors; gene therapy, including use of CC chemokine receptor 5-modified CD4+ T cells; and broadly neutralizing antibody therapy. Success is likely to require a combination of approaches...
April 2018: Topics in Antiviral Medicine
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