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https://www.readbyqxmd.com/read/28430394/structure-based-design-of-a-new-scaffold-for-cell-penetrating-peptidic-inhibitors-of-the-histone-demethylase-phf8
#1
Jerzy Dorosz, Lars Olsen, Signe Teuber Seger, Cornelia Steinhauer, Giorgos Bouras, Charlotte Helgstrand, Anders Wiuf, Michael Gajhede
The histone demethylase PHF8 catalyzes demethylation of mono- and di-methylated lysine 9 on histone H3 (H3K9me1/2) and is a transcriptional activator involved in development and cancer. Affinity and specificity of PHF8 towards H3K9me2 substrate is affected by interaction with both the catalytic domain and a PHD reader domain. The latter specifically recognizes tri-methylated lysine 4 on histone H3. A fragment of the histone H3 tail with tri-methylated lysine 4 was used as template for structure based design of a cyclic, cell-penetrating peptide that exhibits micromolar binding affinity to PHF8 in biochemical assays...
April 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28427935/the-manifolded-dynamics-of-hiv-1-transmission-in-northern-alberta-a-combined-analysis-of-virus-genetic-and-public-health-data
#2
B Vrancken, D Adachi, M Benedet, A Singh, R Read, S Shafran, G D Taylor, S Houston, K Simmonds, S Plitt, C Sikora, P Lemey, C L Charlton, J W Tang
Molecular epidemiology has become a key tool for tracking infectious disease epidemics. Here, the spread of the most prevalent HIV-1 subtypes in Northern Alberta, Canada, was characterized with a Bayesian phylogenetic approach using 1146 HIV-1 pol sequences collected between 2007 and 2013 for routine clinical management purposes. Available patient metadata were qualitatively interpreted and correlated with onwards transmission using Fisher exact tests and logistic regression. Most infections were from subtypes A (n=36), B (n=815) and C (n=211)...
April 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28426837/the-high-prevalence-of-hpv-and-hpv16-european-variants-in-cervical-and-anal-samples-of-hiv-seropositive-women-with-normal-pap-test-results
#3
Lays Paula Bondi Volpini, Neide Aparecida Tosato Boldrini, Luciana Bueno de Freitas, Angelica Espinosa Miranda, Liliana Cruz Spano
Human Immunodeficiency Virus (HIV)-seropositive women are more likely to have anogenital cancer, and high risk-HPV (HR-HPV) infection is the main associated factor. Between August 2013 and December 2015, we conducted a descriptive study to determine the HPV genotypes and HPV16 variants in cervical and anal samples of HIV-seropositive women with a normal Pap test. The viral DNA was amplified by PCR using the PGMY09/11 set of primers. Reverse line blot (RLB), restriction fragment length polymorphism (RFLP) and sequencing assays were used to determine the HPV genotypes...
2017: PloS One
https://www.readbyqxmd.com/read/28426273/preclinical-development-of-bcg-hiva-2auxo-int-harboring-an-integrative-expression-vector-for-a-hiv-tb-pediatric-vaccine-enhancement-of-stability-and-specific-hiv-1-t-cell-immunity
#4
Aakash Mahant, Narcís Saubi, Yoshiki Eto, Núria Guitart, Josep M ª Gatell, Tomáš Hanke, Joan Joseph
One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA(int), expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance...
April 20, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28425872/increase-in-human-immunodeficiency-virus-1-diversity-and-detection-of-various-subtypes-and-recombinants-in-north-eastern-brazil
#5
Kledoaldo Lima, Élcio Leal, Ana Maria Salustiano Cavalcanti, Daniela Medeiros Salustiano, Luzidalva Barbosa de Medeiros, Sirleide Pereira da Silva, Heloísa Ramos Lacerda
PURPOSE: Diverse human immunodeficiency virus 1 (HIV-1) subtypes and circulating recombinant forms are found in Brazil. The majority of HIV-1 molecular epidemiological studies in Brazil have been conducted in the southern and south-eastern regions of the country, although several recent studies in the north-eastern region have addressed this issue. The objective of this study was to molecularly characterize HIV-1 circulating in Pernambuco, north-eastern Brazil. METHODOLOGY: A total of 64 samples were collected from 2002 to 2003, and another 103 were collected from 2007 to 2009...
April 21, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28424286/subtype-specific-differences-in-gag-protease-driven-replication-capacity-are-consistent-with-inter-subtype-differences-in-hiv-1-disease-progression
#6
Marion W Kiguoya, Jaclyn K Mann, Denis Chopera, Kamini Gounder, Guinevere Q Lee, Peter W Hunt, Jeffrey N Martin, T Blake Ball, Joshua Kimani, Zabrina L Brumme, Mark A Brockman, Thumbi Ndung'u
There are marked differences in the spread and prevalence of HIV-1 subtypes worldwide, and differences in clinical progression have been reported. However, the biological reasons underlying these differences are unknown. Gag-protease is essential for HIV-1 replication and Gag-protease-driven replication capacity has previously been correlated with disease progression. We show that Gag-protease replication capacity correlates significantly with that of whole isolates (r=0.51; p=0.04), indicating that Gag-protease is a significant contributor to viral replication capacity...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28422789/antigp41-membrane-proximal-external-region-antibodies-and-the-art-of-using-the-membrane-for-neutralization
#7
Nichole Cerutti, Juan Luis Loredo-Varela, Christophe Caillat, Winfried Weissenhorn
PURPOSE OF REVIEW: We summarize the latest research on the progress to understand the neutralizing epitopes present within the membrane proximal external region (MPER) of the HIV-1 fusion protein subunit gp41. RECENT FINDINGS: The HIV-1 fusion protein subunit gp41 contains a highly conserved sequence that is essential for membrane fusion and targeted by broadly neutralizing antibodies such as 2F5, 4E10, Z13e1, and 10E8. These antibodies recognize a linear gp41 epitope with high affinity, but require additional hydrophobic sequences present in their heavy chain CDR3 for neutralization...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28419276/molecular-features-of-the-v1-v4-coding-region-of-sexually-transmitted-hiv-1
#8
Jun Yong Choi, Sergei L Kosakovsky Pond, Christy M Anderson, Douglas D Richman, Davey M Smith
Background: Investigations into which HIV-1 sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. Methods: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we re-analyzed all available 2,485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed effects linear regression and an approach to approximate the unobserved transmitted virus...
April 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28416661/single-cell-analysis-of-hiv-1-transcriptional-activity-reveals-expression-of-proviruses-in-expanded-clones-during-art
#9
Ann Wiegand, Jonathan Spindler, Feiyu F Hong, Wei Shao, Joshua C Cyktor, Anthony R Cillo, Elias K Halvas, John M Coffin, John W Mellors, Mary F Kearney
Little is known about the fraction of human immunodeficiency virus type 1 (HIV-1) proviruses that express unspliced viral RNA in vivo or about the levels of HIV RNA expression within single infected cells. We developed a sensitive cell-associated HIV RNA and DNA single-genome sequencing (CARD-SGS) method to investigate fractional proviral expression of HIV RNA (1.3-kb fragment of p6, protease, and reverse transcriptase) and the levels of HIV RNA in single HIV-infected cells from blood samples obtained from individuals with viremia or individuals on long-term suppressive antiretroviral therapy (ART)...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28412523/progenitor-strain-introduction-of-mycobacterium-bovis-at-the-wildlife-livestock-interface-can-lead-to-clonal-expansion-of-the-disease-in-a-single-ecosystem
#10
Anzaan Dippenaar, Sven David Charles Parsons, Michele Ann Miller, Tiny Hlokwe, Nicolaas Claudius Gey van Pittius, Sabir Abdu Adroub, Abdallah Musa Abdallah, Arnab Pain, Robin Mark Warren, Anita Luise Michel, Paul David van Helden
Mycobacterium bovis infects multiple wildlife species and domesticated cattle across South Africa, and negatively impacts on livestock trade and movement of wildlife for conservation purposes. M. bovis infection was first reported in the Kruger National Park (KNP) in South Africa during the 1990s, and has since spread to infect numerous animal host species throughout the park and across South Africa. Whole genome sequencing data of 17 M. bovis isolates were analyzed to investigate the genomic diversity among M...
April 12, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28404672/increased-tuberculosis-patient-mortality-associated-with-mycobacterium-tuberculosis-mutations-conferring-resistance-to-second-line-antituberculous-drugs
#11
Sophia B Georghiou, Marva Seifert, Donald G Catanzaro, Richard S Garfein, Timothy C Rodwell
Rapid molecular diagnostics have great potential to limit the spread of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). These technologies detect mutations in the Mycobacterium tuberculosis (Mtb) genome that confer phenotypic drug resistance. However, there is little data published regarding the relationships between the detected Mtb resistance mutations and M/XDR-TB treatment outcomes, limiting our current ability to exploit the full potential of molecular diagnostics. We analyzed clinical, microbiological and sequencing data for 451 patients and their clinical isolates collected in a multinational, observational cohort study to determine if there was an association between Mtb resistance mutations and patient mortality...
April 12, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28404572/an-hiv-envelope-gp120-fc-fusion-protein-elicits-effector-antibody-responses-in-rhesus-macaques
#12
Zhanna Shubin, Weizhong Li, Bhawna Poonia, Guido Ferrari, Celia LaBranche, David Montefiori, Xiaoping Zhu, C David Pauza
A goal for HIV prevention programs is to develop safe and effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env) and seek to improve the quality and quantity of antibodies by altering the sequence, conformation, oligomerization or glycosylation of gp120 to activate appropriate germline B cells and mimic the subsequent maturation pathways seen in infected individuals...
April 12, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28404091/tenofovir-alafenamide-versus-tenofovir-disoproxil-fumarate-for-the-treatment-of-hbeag-positive-chronic-hepatitis-b-virus-infection-a-randomised-double-blind-phase-3-non-inferiority-trial
#13
Henry L Y Chan, Scott Fung, Wai Kay Seto, Wan-Long Chuang, Chi-Yi Chen, Hyung Joon Kim, Aric Josun Hui, Harry L A Janssen, Abhijit Chowdhury, Tak Yin Owen Tsang, Rajiv Mehta, Edward Gane, John F Flaherty, Benedetta Massetto, Anuj Gaggar, Kathryn M Kitrinos, Lanjia Lin, G Mani Subramanian, John G McHutchison, Young-Suk Lim, Subrat K Acharya, Kosh Agarwal
BACKGROUND: Tenofovir alafenamide is a novel prodrug formulated to deliver the active metabolite to target cells more efficiently than tenofovir disoproxil fumarate at a lower dose, thereby reducing systemic exposure. In patients with HIV, tenofovir alafenamide was as efficacious as tenofovir disoproxil fumarate, with reduced bone and renal toxic effects. We compared the efficacy and safety of the two drugs in patients with HBeAg-positive chronic hepatitis B virus (HBV) infection in a non-inferiority study...
November 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28403828/lower-genetic-variability-of-hiv-1-and-antiretroviral-drug-resistance-in-pregnant-women-from-the-state-of-par%C3%A3-brazil
#14
Luiz Fernando Almeida Machado, Iran Barros Costa, Maria Nazaré Folha, Anderson Levy Bessa da Luz, Antonio Carlos Rosário Vallinoto, Ricardo Ishak, Marluisa Oliveira Guimarães Ishak
BACKGROUND: The present study aimed to describe the genetic diversity of HIV-1, as well as the resistance profile of the viruses identified in HIV-1 infected pregnant women under antiretroviral therapy in the state of Pará, Northern Brazil. METHODS: Blood samples were collected from 45 HIV-1 infected pregnant to determine the virus subtypes according to the HIV-1 protease (PR) gene and part of the HIV-1 reverse transcriptase (RT) gene by sequencing the nucleotides of these regions...
April 12, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28403241/characterization-of-a-novel-hiv-1-unique-recombinant-form-between-crf07_bc-and-crf55_01b-in-men-who-have-sex-with-men-in-guangzhou-china
#15
Yue Wu, Xuqi Ren, Dan Yin, Haiying Wang, Zhengwei Wan, Xiufen Li, Guifang Hu, Shixing Tang
Here, we report the genetic diversity of HIV-1 and emergence of novel HIV-1 unique recombinant forms (URF) in both HIV-infected intravenous drug users (IDU) and men who have sex with men (MSM) in Guangzhou, China. We further characterized a novel URF strain isolated from an HIV-infected MSM, GD698. Near full-length genome (NFLG) phylogenic analysis showed that this novel URF was composed of CRF07_BC and CRF55_01B, with two recombinant breakpoints (nt 6,003 and 8,251 relative to the HXB2 genome) in the vpu/env and env genes, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28402975/frequent-pul27-variations-in-hiv-infected-patients
#16
Azam Mirarab, Alireza Mohebbi, Abdolvahab Moradi, Naeme Javid, Mohammad Ali Vakili, Alijan Tabarraei
OBJECTIVE: Drug-resistant isolates of human cytomegalovirus (HCMV) have led to the development of new anti-HCMV drugs. Maribavir (MBV) is a novel inhibitor of the HCMV viral kinase. Resistance to MBV is mapped to gene UL27, a viral nuclear protein. In this study, we investigated UL27 polymorphisms in MBV-naive HIV-positive and HCMV congenitally infected clinical samples. METHODS: DNA was extracted from 20 CMV-positive HIV (9/20) and congenitally infected (11/20) patients and used for UL27 polymerase chain reaction amplification...
April 13, 2017: Intervirology
https://www.readbyqxmd.com/read/28402447/infectious-disease-dynamics-inferred-from-genetic-data-via-sequential-monte-carlo
#17
R A Smith, E L Ionides, A A King
Genetic sequences from pathogens can provide information about infectious disease dynamics that may supplement or replace information from other epidemiological observations. Most currently available methods first estimate phylogenetic trees from sequence data, then estimate a transmission model conditional on these phylogenies. Outside limited classes of models, existing methods are unable to enforce logical consistency between the model of transmission and that underlying the phylogenetic reconstruction. Such conicts in assumptions can lead to bias in the resulting inferences...
April 8, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28401776/molecular-characteristics-of-the-envelope-of-vertically-transmitted-hiv-1-strains-from-infants-with-hiv-infection
#18
Manickam Ashokkumar, Manohar Nesakumar, Cheedarla Narayanaiah, Vidya Vijayan Kk, Babu Hemalatha, Srikanth P Tripathy, Luke Elizabeth Hanna
Mother-to-child transmission of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV infected infants (< 2 years)...
April 12, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28401492/the-alphabet-soup-of-hiv-reservoir-markers
#19
REVIEW
Radwa R Sharaf, Jonathan Z Li
PURPOSE OF REVIEW: Despite the success of antiretroviral therapy in suppressing HIV, life-long therapy is required to avoid HIV reactivation from long-lived viral reservoirs. Currently, there is intense interest in searching for therapeutic interventions that can purge the viral reservoir to achieve complete remission in HIV patients off antiretroviral therapy. The evaluation of such interventions relies on our ability to accurately and precisely measure the true size of the viral reservoir...
April 11, 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28399968/tuberculosis-resistance-conferring-mutations-with-fitness-cost-among-hiv-positive-individuals-in-uganda
#20
W Ssengooba, D Lukoye, C J Meehan, D P Kateete, M L Joloba, B C de Jong, F G Cobelens, F van Leth
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is considered to be less transmissible due to the fitness cost associated with drug resistance-conferring mutations in essential genes. OBJECTIVE: To test the hypothesis that TB drug resistance-conferring mutations with fitness cost are more frequent among human immunodeficiency virus (HIV) positive than among HIV-negative patients. DESIGN: We analysed all strains from the two TB drug resistance surveys conducted in Uganda between 2008 and 2011...
May 1, 2017: International Journal of Tuberculosis and Lung Disease
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