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https://www.readbyqxmd.com/read/28930470/structure-related-roles-for-the-conservation-of-the-hiv-1-fusion-peptide-sequence-revealed-by-nmr
#1
Soraya Serrano, Nerea Huarte, Edurne Rujas, David Andreu, Jose L Nieva, M Angeles Jimenez
Despite extensive characterization of the human immunodeficiency virus type-1 (HIV-1) hydrophobic fusion peptide (FP), the structure-function relationships underlying its extraordinary degree of conservation remain poorly understood. Specifically, the fact that the tandem repeat of the tripeptide FLGFLG is absolutely conserved suggests that high hydrophobicity may not suffice to unleash FP function. Here, we have compared the NMR structures adopted in nonpolar media by two FP surrogates, wtFP-tag and scrFP-tag, which had equal hydrophobicity but contained wild-type and scrambled core sequences LFLGFLG and FGLLGFL, respectively...
September 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28918303/decoding-noises-in-hiv-computational-genotyping
#2
MingRui Jia, Timothy Shaw, Xing Zhang, Dong Liu, Ye Shen, Amara E Ezeamama, Chunfu Yang, Ming Zhang
Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline...
September 14, 2017: Virology
https://www.readbyqxmd.com/read/28918033/six-highly-conserved-targets-of-rnai-revealed-in-hiv-1-infected-patients-from-russia-are-also-present-in-many-hiv-1-strains-worldwide
#3
Olga V Kretova, Daria M Fedoseeva, Maria A Gorbacheva, Natalya M Gashnikova, Maria P Gashnikova, Nataliya V Melnikova, Vladimir R Chechetkin, Yuri V Kravatsky, Nickolai A Tchurikov
RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%-97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT), integrase, vpu, gp120, and p17...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28914817/ledgf-p75-deficiency-increases-deletions-at-the-hiv-1-cdna-ends
#4
Murilo T D Bueno, Daniel Reyes, Manuel Llano
Processing of unintegrated linear HIV-1 cDNA by the host DNA repair system results in its degradation and/or circularization. As a consequence, deficient viral cDNA integration generally leads to an increase in the levels of HIV-1 cDNA circles containing one or two long terminal repeats (LTRs). Intriguingly, impaired HIV-1 integration in LEDGF/p75-deficient cells does not result in a correspondent increase in viral cDNA circles. We postulate that increased degradation of unintegrated linear viral cDNA in cells lacking the lens epithelium-derived growth factor (LEDGF/p75) account for this inconsistency...
September 15, 2017: Viruses
https://www.readbyqxmd.com/read/28912478/the-molecular-epidemiology-of-hiv-1-in-the-comunidad-valenciana-spain-analysis-of-transmission-clusters
#5
Juan Ángel Patiño-Galindo, Manoli Torres-Puente, María Alma Bracho, Ignacio Alastrué, Amparo Juan, David Navarro, María José Galindo, Dolores Ocete, Enrique Ortega, Concepción Gimeno, Josefina Belda, Victoria Domínguez, Rosario Moreno, Fernando González-Candelas
HIV infections are still a very serious concern for public heath worldwide. We have applied molecular evolution methods to study the HIV-1 epidemics in the Comunidad Valenciana (CV, Spain) from a public health surveillance perspective. For this, we analysed 1804 HIV-1 sequences comprising protease and reverse transcriptase (PR/RT) coding regions, sampled between 2004 and 2014. These sequences were subtyped and subjected to phylogenetic analyses in order to detect transmission clusters. In addition, univariate and multinomial comparisons were performed to detect epidemiological differences between HIV-1 subtypes, and risk groups...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28910384/correction-rare-hiv-1-transmitted-founder-lineages-identified-by-deep-viral-sequencing-contribute-to-rapid-shifts-in-dominant-quasispecies-during-acute-and-early-infection
#6
Gustavo H Kijak, Eric Sanders-Buell, Agnes-Laurence Chenine, Michael A Eller, Nilu Goonetilleke, Rasmi Thomas, Sivan Leviyang, Elizabeth A Harbolick, Meera Bose, Phuc Pham, Celina Oropeza, Kultida Poltavee, Anne Marie O'Sullivan, Erik Billings, Melanie Merbah, Margaret C Costanzo, Joanna A Warren, Bonnie Slike, Hui Li, Kristina K Peachman, Will Fischer, Feng Gao, Claudia Cicala, James Arthos, Leigh A Eller, Robert J O'Connell, Samuel Sinei, Lucas Maganga, Hannah Kibuuka, Sorachai Nitayaphan, Mangala Rao, Mary A Marovich, Shelly J Krebs, Morgane Rolland, Bette T Korber, George M Shaw, Nelson L Michael, Merlin L Robb, Sodsai Tovanabutra, Jerome H Kim
[This corrects the article DOI: 10.1371/journal.ppat.1006510.].
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28902072/hiv-transmission-dynamics-among-foreign-born-persons-in-the-united-states
#7
Eduardo E Valverde, Alexandra M Oster, Songli Xu, Joel O Wertheim, Angela L Hernandez
BACKGROUND: In the United States (U.S.), foreign-born persons are disproportionately affected by HIV and differ epidemiologically from U.S.-born persons with diagnosed HIV infection. Understanding HIV transmission dynamics among foreign-born persons is important to guide HIV prevention efforts for these populations. We conducted molecular transmission network analysis to describe HIV transmission dynamics among foreign-born persons with diagnosed HIV. METHODS: Using HIV-1 polymerase nucleotide sequences reported to the U...
September 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28899424/clade-homogeneity-and-low-rate-of-delta-virus-despite-hyperendemicity-of-hepatitis-b-virus-in-ethiopia
#8
Yeshambel Belyhun, Uwe Gerd Liebert, Melanie Maier
BACKGROUND: Although hepatitis B virus (HBV) is hyperendemic and heterogeneous in its genetic diversity in Ethiopia, little is known about hepatitis D virus (HDV) circulating genotypes and molecular diversity. METHODS: A total of 321 hepatitis B surface antigen (HBsAg) positives (125 HIV co-infected, 102 liver disease patients and 94 blood donors) were screened for anti-HDV antibody. The anti-HDV positive sera were subjected to Real time PCR for HDV-RNA confirmation...
September 12, 2017: Virology Journal
https://www.readbyqxmd.com/read/28899102/community-based-antiretroviral-treatment-in-rural-zimbabwe
#9
Benjamin Chimukangara, Justen Manasa, Rebecca Mitchell, Georgina Nyabadza, David Katzenstein, Collen Masimirembwa
INTRODUCTION: Treatment of HIV has reduced HIV/AIDS-related mortality. Sustaining >90% virologic suppression in sub-Saharan Africa requires decentralized care and prevention services to rural communities. In Zimbabwe, the number of people receiving ART has increased rapidly. However, access to treatment monitoring tools such as viral load and drug resistance testing is limited. We assessed virologic treatment outcomes among ART recipients in Nyamutora, a rural community receiving bimonthly ART and prevention services...
September 13, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28895527/assessing-the-danger-of-self-sustained-hiv-epidemics-in-heterosexuals-by-population-based-phylogenetic-cluster-analysis
#10
Teja Turk, Nadine Bachmann, Claus Kadelka, Jürg Böni, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Manuel Battegay, Enos Bernasconi, Alexandra Calmy, Matthias Cavassini, Hansjakob Furrer, Matthias Hoffmann, Huldrych F Günthard, Roger D Kouyos
Assessing the danger of transition of HIV transmission from a concentrated to a generalized epidemic is of major importance for public health. In this study, we develop a phylogeny-based statistical approach to address this question. As a case study, we use this to investigate the trends and determinants of HIV transmission among Swiss heterosexuals. We extract the corresponding transmission clusters from a phylogenetic tree. To capture the incomplete sampling, the delayed introduction of imported infections to Switzerland, and potential factors associated with basic reproductive number R0, we extend the branching process model to infer transmission parameters...
September 12, 2017: ELife
https://www.readbyqxmd.com/read/28893790/combinatorial-crispr-cas9-and-rnai-attack-on-hiv-1-dna-and-rna-can-lead-to-cross-resistance
#11
Na Zhao, Gang Wang, Atze T Das, Ben Berkhout
Many potent antiviral drugs have been developed against HIV-1 and their combined action is usually successful in achieving durable virus suppression in infected individuals. This success is based on two effects: additive or even synergistic virus inhibition and an increase in the genetic threshold for development of drug-resistance. More recently, several genetic approaches have been developed to attack the HIV-1 genome in a gene therapy setting. We set out to test the combinatorial possibilities for a therapy based on the CRISPR-Cas9 and RNA interference (RNAi) mechanisms that attack the viral DNA and RNA, respectively...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28893290/evasion-of-adaptive-immunity-by-hiv-through-the-action-of-host-apobec3g-f-enzymes
#12
REVIEW
Michael Grant, Mani Larijani
APOBEC3G (A3G) and APOBEC3F (A3F) are DNA-mutating enzymes expressed in T cells, dendritic cells and macrophages. A3G/F have been considered innate immune host factors, based on reports that they lethally mutate the HIV genome in vitro. In vivo, A3G/F effectiveness is limited by viral proteins, entrapment in inactive complexes and filtration of mutations during viral life cycle. We hypothesized that the impact of sub-lethal A3G/F action could extend beyond the realm of innate immunity confined to the cytoplasm of infected cells...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28893274/modulation-of-the-strength-and-character-of-hiv-specific-cd8-t-cell-responses-with-heteroclitic-peptides
#13
REVIEW
Kayla A Holder, Michael D Grant
Chronic infection with human immunodeficiency virus (HIV) causes HIV-specific CD8(+) T cell dysfunction and exhaustion. The strong association between non-progression and maintenance of HIV-specific CD8(+) T cell cytokine production and proliferative capacities suggests that invigorating CD8(+) T cell immune responses would reduce viremia and slow disease progression. A series of studies have demonstrated that sequence variants of native immunogenic peptides can generate more robust CD8(+) T cell responses and that stimulation with these 'heteroclitic' peptides can steer responses away from the phenotypic and functional attributes of exhaustion acquired during chronic HIV infection...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28893272/killed-whole-hiv-vaccine-employing-a-well-established-strategy-for-antiviral-vaccines
#14
REVIEW
C Yong Kang, Yong Gao
The development of an efficient prophylactic HIV vaccine has been one of the major challenges in infectious disease research during the last three decades. Here, we present a mini review on strategies employed for the development of HIV vaccines with an emphasis on a well-established vaccine technology, the killed whole-virus vaccine approach. Recently, we reported an evaluation of the safety and the immunogenicity of a genetically modified and killed whole-HIV-1 vaccine designated as SAV001 [1]. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence of the Env signal peptide with that of honeybee melittin to produce an avirulent and replication efficient HIV-1...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28893268/a-novel-hiv-vaccine-targeting-the-protease-cleavage-sites
#15
REVIEW
Hongzhao Li, Robert W Omange, Francis A Plummer, Ma Luo
HIV preferentially infects activated CD4+ T cells and mutates rapidly. The classical vaccine approach aimed to generate broad immune responses to full HIV proteins largely failed to address the potential adverse impact of increased number of activated CD4+ T cells as viral targets. Learning from natural immunity observed in a group of HIV resistant Kenyan female sex workers, we are testing a novel vaccine approach. It focuses immune response to the highly conserved sequences surrounding the HIV protease cleavage sites (PCS) to disrupt viral maturation, while limiting excessive immune activation...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28891788/week-48-resistance-analysis-of-elvitegravir-cobicistat-emtricitabine-tenofovir-df-versus-atazanavir-ritonavir-emtricitabine-tenofovir-df-in-hiv-1-infected-women-waves-study-gs-us-236-0128
#16
Rima Kulkarni, Sally L Hodder, Huyen Cao, Silvia Chang, Michael D Miller, Kirsten L White
Background Women and those with non-B subtype HIV-1 are typically underrepresented in clinical trials. WAVES (GS-US-236-0128) was a double-blind phase 3b study among treatment-naïve HIV-1-infected women that demonstrated that elvitegravir/cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF; N = 289) was superior to atazanavir + ritonavir + FTC/TDF (ATV + RTV + FTC/TDF; N = 286) for HIV-1 RNA < 50 copies/mL by FDA snapshot analysis at week 48. Here, we describe resistance development through week 48 in women with virologic failure and determine the impact of pre-existing mutations and HIV-1 subtype on viral suppression...
July 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28890504/an-alarmingly-high-proportion-of-anti-retroviral-drugs-resistant-hiv-1-infection-among-high-risk-groups-in-central-vietnam-a-sub-study-of-the-national-sentinel-survey
#17
Hung Thai Do, Dong Thanh Nguyen, Lan Anh Thi Nguyen, Duong Huy Do, Huy Xuan Le, Xuan Mai Thi Trinh, Hong Vy Nu Ton, Ikumi Sawada, Noriko Kitamura, Nhat Minh Le, Keisuke Yoshihara, Thu Huong Thi Phan, Chien Trong Bui, Koya Ariyoshi, Lay Myint Yoshida
We investigated the prevalence of HIV drug resistance among high risk groups such as injecting drug user (IDU), female sex worker (FSW) and men having sex with men (MSM) in central Vietnam. We used HIV positive samples from 2012-2013 sentinel surveillance surveys. Study subjects were screened for HIV infection by standardized screening assays and the positive samples were further tested for HIV viral load and drug resistant mutations by in-house assays. Drug resistant mutations (DRMs) were determined using the Stanford University online sequence analysis tool...
September 11, 2017: Japanese Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28887441/hiv-1-mediated-insertional-activation-of-stat5b-and-bach2-trigger-viral-reservoir-in-t-regulatory-cells
#18
Daniela Cesana, Francesca R Santoni de Sio, Laura Rudilosso, Pierangela Gallina, Andrea Calabria, Stefano Beretta, Ivan Merelli, Elena Bruzzesi, Laura Passerini, Silvia Nozza, Elisa Vicenzi, Guido Poli, Silvia Gregori, Giuseppe Tambussi, Eugenio Montini
HIV-1 insertions targeting BACH2 or MLK2 are enriched and persist for decades in hematopoietic cells from patients under combination antiretroviral therapy. However, it is unclear how these insertions provide such selective advantage to infected cell clones. Here, we show that in 30/87 (34%) patients under combination antiretroviral therapy, BACH2, and STAT5B are activated by insertions triggering the formation of mRNAs that contain viral sequences fused by splicing to their first protein-coding exon. These chimeric mRNAs, predicted to express full-length proteins, are enriched in T regulatory and T central memory cells, but not in other T lymphocyte subsets or monocytes...
September 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28884263/efficient-propagation-of-archetype-jc-polyomavirus-in-cos-7-cells-evaluation-of-rearrangements-within-the-nccr-structural-organization-after-transfection
#19
Carla Prezioso, Daniela Scribano, Anna Bellizzi, Elena Anzivino, Donatella Maria Rodio, Maria Trancassini, Anna Teresa Palamara, Valeria Pietropaolo
John Cunningham virus (JCPyV) is an ubiquitous human pathogen that causes disease in immunocompromised patients. The JCPyV genome is composed of an early region and a late region, which are physically separated by the non-coding control region (NCCR). The DNA sequence of the NCCR distinguishes two forms of JCPyV, the designated archetype and the prototype, which resulted from a rearrangement of the archetype sequence. To date, the cell culture systems for propagating JCPyV archetype have been very limited in their availability and robustness...
September 7, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28883821/hidden-lineage-complexity-of-glycan-dependent-hiv-1-broadly-neutralizing-antibodies-uncovered-by-digital-panning-and-native-like-gp140-trimer
#20
Linling He, Xiaohe Lin, Natalia de Val, Karen L Saye-Francisco, Colin J Mann, Ryan Augst, Charles D Morris, Parisa Azadnia, Bin Zhou, Devin Sok, Gabriel Ozorowski, Andrew B Ward, Dennis R Burton, Jiang Zhu
Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs) are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, we examined antibody libraries constructed from donor-17, the source of glycan-dependent PGT121-class bNAbs recognizing the N332 supersite on the HIV-1 envelope glycoprotein. To facilitate this analysis, a digital panning method was devised that combines biopanning of phage-displayed antibody libraries, 900 bp long-read next-generation sequencing, and heavy/light (H/L)-paired antibodyomics...
2017: Frontiers in Immunology
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