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https://www.readbyqxmd.com/read/27933723/comfa-topomer-comfa-and-hqsar-studies-on-a-series-of-novel-hiv-1-protease-inhibitors
#1
Afsane Heidari, Mohammad H Fatemi
Comparative molecular field analysis (CoMFA), topomer CoMFA and hologram QSAR (HQSAR) as three efficient methods of QSAR have been performed on 40 newly synthesized inhibitors against HIV-1 protease. Molecular alignment was done by aid of crystallographic structure of template inhibitor (indirectly alignment) and also by the molecular mechanic (MM) minimized structure. Both alignment methods produced satisfactory statistics for training set, but indirectly alignment had more predictive power. Generated counter maps, especially by topomer CoMFA, give comprehensive information about structural features affecting the inhibitory activities of studied chemicals...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933338/progress-in-research-and-application-of-hiv-1-tat-derived-cell-penetrating-peptide
#2
REVIEW
Le Zou, Qilin Peng, Ping Wang, Boting Zhou
Human immunodeficiency virus type I (HIV-1) transactivator of transcription (TAT) is encoded by HIV-1. It is a peptide rich in basic amino acids and belongs to the protein transduction domain family. It has been found that HIV-1 TAT and its core peptide segment TAT47-57 play an important role in promoting the cellular uptake of coupled bioactive macromolecules, such as peptides, proteins, oligonucleotides, and drug molecules. HIV-1 TAT can also significantly increase the soluble expression of extrinsic proteins...
December 8, 2016: Journal of Membrane Biology
https://www.readbyqxmd.com/read/27932619/ontogeny-of-cd4-t-lymphocytes-with-phenotypic-susceptibility-to-hiv-1-during-exclusive-and-non-exclusive-breastfeeding-in-hiv-1-exposed-ugandan-infants
#3
Elizabeth J McFarland, Tina M Powell, Carolyne Onyango-Makumbi, Weiming Zhang, Kelsey Melander, Prossy Naluyima, Samuel Okurut, Michael A Eller, Mary Glenn Fowler, Edward N Janoff
BACKGROUND: Among HIV-1-exposed infants, mixed breastfeeding is associated with higher postnatal HIV-1 transmission than exclusive breastfeeding, but the mechanisms of this differential risk are uncertain. METHODS: HIV-1-exposed, Ugandan infants were prospectively assessed over the first year of life for feeding practices and T cell maturation, intestinal homing (β7(hi)), activation, and HIV-1 co-receptor (CCR5) expression in peripheral blood. Infants receiving only breast milk and those with introduction of other foods prior to 6 months, categorized as exclusive and non-exclusive, respectively...
December 8, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27932583/inhibition-of-hiv-1-gag-membrane-interactions-by-specific-rnas
#4
Gabrielle C Todd, Alice A Duchon, Jingga Inlora, Erik D Olson, Karin Musier-Forsyth, Akira Ono
HIV-1 particle assembly, which occurs at the plasma membrane (PM) of cells, is driven by the viral polyprotein, Gag. Gag recognizes phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2], a PM-specific phospholipid, via the highly basic region (HBR) in its N-terminal matrix (MA) domain. The HBR is also known to bind to RNA. We have previously shown using an in vitro liposome binding assay that RNA inhibits Gag binding to membranes that lack PI(4,5)P2. If this RNA block is removed by RNase treatment, Gag can bind non-specifically to other negatively charged membranes...
December 8, 2016: RNA
https://www.readbyqxmd.com/read/27932056/sexual-orientation-disparities-in-the-utilization-of-sexual-health-services-in-a-national-probability-sample-of-u-s-women
#5
Madina Agénor, Christina A Muzny, Vanessa Schick, Erika L Austin, Jennifer Potter
Although sexual minority women are at risk of sexually transmitted infections (STIs) and cervical cancer, few nationally representative studies have assessed sexual orientation disparities in sexual health care among women. Using data from the 2011-2013 and 2013-2015 waves of the National Survey of Family Growth, which provide a national probability sample of U.S. women aged 15-44years (N=11.300), we used multivariable logistic regression to examine the associations between sexual behavior and sexual identity (modeled separately) and STI testing in the past year, Pap test use in the last 3years, lifetime HIV testing, and lifetime human papillomavirus (HPV) testing...
December 5, 2016: Preventive Medicine
https://www.readbyqxmd.com/read/27930881/ultraslow-domain-motions-in-hiv-1-tar-rna-revealed-by-solid-state-deuterium-nmr
#6
Wei Huang, Prashant S Emani, Gabriele Varani, Gary P Drobny
Intrinsic motions may allow HIV-1 TAR RNA to change its conformation to form a functional complex with the Tat protein, which is essential for viral replication. Understanding the dynamic properties of TAR necessitates determining motion on the intermediate ns-μs time scale. To this end, we performed solid-state deuterium NMR line shape and T1Z relaxation time experiments to measure intermediate motions for two uridine residues, U40 and U42, within the lower helix of TAR. We infer global motions at rates of ~10(5) s(-1) in the lower helix, which are much slower than those of the upper helix (~10(6) s(-1)), indicating the two helical domains reorient independently of one another in the solid-state sample...
December 8, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27930600/increased-frequency-of-cd39-cd56-bright-natural-killer-cells-in-hiv-1-infection-correlates-with-immune-activation-and-disease-progression
#7
Patrick Dierks, Raluca Wroblewski, Johanna M Eberhard, Gloria Martrus, Olaf Degen, Sandra Hertling, Stefan Schmiedel, Sebastian Lunemann, Anja Hüfner, Ansgar W Lohse, Marcus Altfeld, Jan van Lunzen, Julian Schulze Zur Wiesch
The expression pattern of the ectonucleotidases CD39 and CD73 on NK cells was examined in PBMC of 61 HIV-1 infected patients. Increased frequencies of CD39CD56 NK cells were detectable in untreated HIV patients, which was associated with high viral load, low CD4+ T cell count and CD8+ T cell activation. Additionally, levels of CD39 on NK cells were inducible by in vitro stimulation of NK cells, correlating with Aryl hydrocarbon receptor (AHR) and IL-10 expression. Here, we provide first evidence of increased CD39CD56 NK cell frequencies during HIV infection, which might have consequences for NK cell function and HIV pathogenesis...
December 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/27928921/discovery-of-natural-mouse-serum-derived-hiv-1-entry-inhibitor-s
#8
M Wei, Y Chen, J Xi, S Ru, M Ji, D Zhang, Q Fang, B Tang
Among rationally designed human immunodeficiency virus 1 (HIV-1) inhibitors, diverse natural factors have showed as potent anti-HIV activity in human blood. We have discovered that the boiled supernatant of healthy mouse serum could suppress HIV-1 entry, and exhibited reduced inhibitory activity after trypsin digestion. Further analysis demonstrated that only the fraction containing 10-25 K proteins could inhibit HIV-1 mediated cell-cell fusion. These results suggest that the 10-25 K protein(s) is novel natural HIV-1 entry inhibitor(s)...
2016: Acta Virologica
https://www.readbyqxmd.com/read/27928907/separation-of-hiv-1-gag-virus-like-particles-from-vesicular-particles-impurities-by-hydroxyl-functionalized-monoliths
#9
Petra Steppert, Daniel Burgstaller, Miriam Klausberger, Petra Kramberger, Andres Tover, Eva Berger, Katharina Nöbauer, Ebrahim Razzazi-Fazeli, Alois Jungbauer
The downstream processing of enveloped virus-like particles is very challenging because of the biophysical and structural similarity between correctly assembled particles and contaminating vesicular particles present in the feedstock. We used hydroxyl-functionalized polymethacrylate monoliths, providing hydrophobic and electrostatic binding contributions, for the purification of HIV-1 gag virus-like particles. The clarified culture supernatant was conditioned with ammonium sulfate and after membrane filtration, loaded onto a 1 mL monolith...
December 8, 2016: Journal of Separation Science
https://www.readbyqxmd.com/read/27928057/modulation-of-the-splicing-regulatory-function-of-srsf10-by-a-novel-compound-that-impairs-hiv-1-replication
#10
Lulzim Shkreta, Marco Blanchette, Johanne Toutant, Emmanuelle Wilhelm, Brendan Bell, Benjamin A Story, Ahalya Balachandran, Alan Cochrane, Peter K Cheung, P Richard Harrigan, David S Grierson, Benoit Chabot
We recently identified the 4-pyridinone-benzisothiazole carboxamide compound 1C8 as displaying strong anti-HIV-1 potency against a variety of clinical strains in vitro Here we show that 1C8 decreases the expression of HIV-1 and alters splicing events involved in the production of HIV-1 mRNAs. Although 1C8 was designed to be a structural mimic of the fused tetracyclic indole compound IDC16 that targets SRSF1, it did not affect the splice site shifting activity of SRSF1. Instead, 1C8 altered splicing regulation mediated by SRSF10...
December 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27928019/tlr2-ligation-enhances-hiv-1-replication-in-activated-ccr6-cd4-t-cells-by-increasing-virus-entry-and-establishing-a-more-permissive-environment-to-infection
#11
Jean-François Bolduc, Michel Ouellet, Laurent Hany, Michel J Tremblay
: In this study, we investigated the effect of TLR2 ligation on the permissiveness of activated CD4(+) T cells to HIV-1 infection by focusing our experiments on the relative susceptibility of cell subsets based on their expression of CCR6. Purified primary human CD4(+) T cells were first subjected to a CD3/CD28 costimulation before treatment with the TLR2 agonist Pam3CSK4. Finally, cells were inoculated with R5-tropic HIV-1 particles that permit to study the effect of TLR2 triggering on virus production at both population and single-cell levels...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27928014/histidine-375-modulates-cd4-binding-in-hiv-1-crf01_ae-envelope-glycoproteins
#12
Daria Zoubchenok, Maxime Veillette, Jérémie Prévost, Eric Sanders-Buell, Kshitij Wagh, Bette Korber, Agnès L Chenine, Andrés Finzi
: The envelope glycoproteins (Env) from human immunodeficiency virus type 1 (HIV-1) mediate viral entry. The binding of the HIV-1 gp120 glycoprotein to CD4 triggers conformational changes in gp120 that allow high-affinity binding to its coreceptors. Contrary to all other Envs from the same phylogenetic group M, which possess a serine (S) at position 375, those from CRF01_AE strains possess a histidine (H) at this location. This residue is part of the Phe43 cavity where residue 43 of CD4 (a phenylalanine) engages with the gp120...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27928009/influence-of-plasma-cell-niche-factors-on-the-recruitment-and-maintenance-of-irf4hi-plasma-cells-and-plasmablasts-in-vaccinated-siv-infected-rhesus-macaques-with-low-and-high-viremia
#13
Julia M Shaw, Leia K Miller-Novak, Venkatramanan Mohanram, Katherine McKinnon, Thorsten Demberg, Diego A Vargas-Inchaustegui, David Venzon, Marjorie Robert-Guroff
: In a recent study, we found protection following SIV exposure correlated with rectal plasma cell frequency in vaccinated female rhesus macaques. We sought to determine if these same macaques maintained high mucosal plasma cell frequencies post-infection and if this translated to reduced viremia. Although delayed SIV acquisition did not predict subsequent viral control, alterations existed in the distribution of plasma cells and plasmablasts between macaques that exhibited high or low viremia...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27928004/the-effect-of-hiv-1-env-on-serinc5-antagonism
#14
Saina Beitari, Shilei Ding, Qinghua Pan, Andrés Finzi, Chen Liang
: SERINC5 is able to restrict HIV-1 infection by drastically impairing the infectivity of viral particles. Current studies have shown that HIV-1 Nef protein counters SERINC5 through down regulating SERINC5 from the cell surface and preventing virion incorporation of SERINC5. In addition, the Env proteins of some HIV-1 strains can also overcome SERINC5 inhibition. However, it is unclear how HIV-1 Env does so and why HIV-1 has two mechanisms to resist SERINC5 inhibition. Results of this study show that neither Env nor Nef prevents high-level ectopic SERINC5 from incorporation into HIV-1 particles, except that Env, but not Nef, is able to resist the inhibition of virion-associated SERINC5...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27926927/male-circumcision-and-the-epidemic-emergence-of-hiv-2-in-west-africa
#15
João Dinis Sousa, Marina Padrão Temudo, Barry Stephen Hewlett, Ricardo Jorge Camacho, Viktor Müller, Anne-Mieke Vandamme
BACKGROUND: Epidemic HIV-2 (groups A and B) emerged in humans circa 1930-40. Its closest ancestors are SIVsmm infecting sooty mangabeys from southwestern Côte d'Ivoire. The earliest large-scale serological surveys of HIV-2 in West Africa (1985-91) show a patchy spread. Côte d'Ivoire and Guinea-Bissau had the highest prevalence rates by then, and phylogeographical analysis suggests they were the earliest epicenters. Wars and parenteral transmission have been hypothesized to have promoted HIV-2 spread...
2016: PloS One
https://www.readbyqxmd.com/read/27924779/hepatic-safety-of-maraviroc-in-patients-with-hiv-1-and-hepatitis-c-and-or-b-virus-144-week-results-from-a-randomized-placebo-controlled-trial
#16
Juergen K Rockstroh, Frank Plonski, Meena Bansal, Gerd Fätkenheuer, Catherine B Small, David M Asmuth, Gilles Pialoux, Rebecca Zhang-Roper, Ronnie Wang, Juan A Pineda, Jayvant Heera
BACKGROUND: In the primary 48-week analysis of a hepatic safety trial in patients with HIV-1 co-infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), maraviroc-containing treatment regimens were not associated with increased hepatotoxicity. METHODS: In this randomised, double-blind, placebo-controlled, multicentre study, patients received maraviroc twice daily (n=70) or placebo (n=67) with concomitant antiretroviral therapy for 144 weeks (clinicaltrials...
December 7, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27923951/maternal-antibody-responses-and-nonprimary-congenital-cytomegalovirus-infection-of-hiv-1-exposed-infants
#17
Kristy M Bialas, Daniel Westreich, Eduardo Cisneros de la Rosa, Cody S Nelson, Lawrence M Kauvar, Tong-Ming Fu, Sallie R Permar
Risk of congenital cytomegalovirus (cCMV) transmission is highly dependent on the presence of preexisting maternal immunity, with the lowest rates observed in CMV-seroimmune populations. Among infants of CMV-seroimmune women, those who are exposed to human immunodeficiency virus (HIV) have an increased risk of acquiring cCMV infection as compared to HIV-unexposed infants. To better understand the risk factors of nonprimary cCMV transmission in HIV-infected women, we performed a case-control study in which CMV-specific plasma antibody responses from 19 CMV-transmitting and 57 CMV-nontransmitting women with chronic CMV/HIV coinfection were evaluated for the ability to predict the risk of cCMV infection...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27923946/prevalence-of-antiretroviral-drug-resistance-in-patients-who-are-not-responding-to-protease-inhibitor-based-treatment-results-from-the-first-national-survey-in-south-africa
#18
K Steegen, M Bronze, M A Papathanasopoulos, G van Zyl, D Goedhals, C Van Vuuren, W Macleod, I Sanne, W S Stevens, S C Carmona
Limited data exist on human immunodeficiency virus type 1 (HIV-1) resistance in patients who are not responding to protease inhibitor (PI)-based regimens in resource-limited settings. This study assessed resistance profiles in adults across South Africa who were not responding to PI-based regimens. pol sequencing was undertaken and submitted to the Stanford HIV Drug Resistance Database. At least 1 major PI mutation was detected in 16.4% of 350 participants. A total of 53.4% showed intermediate resistance to darunavir/ritonavir, whereas high-level resistance was not observed...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27922857/comprehensive-assessment-of-the-arginine-pathway-and-its-relationship-to-inflammation-in-hiv
#19
Sahera Dirajlal-Fargo, S M Khurshid Alam, Abdus Sattar, Manjusha Kulkarni, Nicholas Funderburg, W H Wilson Tang, Grace A Mccomsey
BACKGROUND: Nitric oxide helps maintain vascular function and is generated through the oxidation of arginine. Whether altered arginine metabolism may lead to elevated levels of inflammation in HIV is unclear. METHODS: We performed a cross-sectional analysis of HIV-infected adults on stable ART with HIV-1 RNA < 50 copies/mL and HIV-uninfected controls. We measured biomarkers in the arginine pathway, markers of systemic inflammation, and monocyte activation. T-tests, chi-square tests and propensity score matching analyses were used to compare markers by HIV status, and multiple linear regressions were used to assess associations of arginine metabolites with markers of inflammation...
December 5, 2016: AIDS
https://www.readbyqxmd.com/read/27922453/safety-and-efficacy-of-the-hiv-1-attachment-inhibitor-prodrug-fostemsavir-in-antiretroviral-experienced-subjects-week-48-analysis-of-ai438011-a-phase-iib-randomized-controlled-trial
#20
Melanie Thompson, Jacob P Lalezari, Richard Kaplan, Yvett Pinedo, Otto A Sussmann Pena, Pedro Cahn, David A Stock, Samit R Joshi, George J Hanna, Max Lataillade
BACKGROUND: Fostemsavir is a prodrug of temsavir, an attachment inhibitor that binds directly to HIV-1 gp120, blocking initial viral attachment and entry into host CD4 cells. Efficacy, safety, and dose-response data of fostemsavir in treatment-experienced, HIV-1-infected subjects, through Week 48, are reported. METHODS: AI438011 is an ongoing Phase IIb, randomized, active-controlled trial (NCT01384734). Subjects were randomized 1:1:1:1:1 into five arms: fostemsavir (400 mg twice daily [BID], 800 mg BID, 600 mg once daily [QD], or 1200 mg QD), and a reference arm (ritonavir-boosted atazanavir [ATV/r] 300/100 mg QD), each with a backbone of raltegravir 400 mg BID + tenofovir disoproxil fumarate 300 mg QD...
December 6, 2016: Antiviral Therapy
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