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https://www.readbyqxmd.com/read/28213870/molecular-characterization-of-bovine-leukemia-virus-from-moldovan-dairy-cattle
#1
Aneta Pluta, Marzena Rola-Łuszczak, Piotr Kubiś, Svetlana Balov, Roman Moskalik, Bhudipa Choudhury, Jacek Kuźmak
Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL), a disease that has worldwide distribution. Whilst it has been eradicated in most of Western Europe and Scandinavia, it remains a problem in other regions, particularly Eastern Europe and South America. For this study, in 2013, 24 cattle from three farms in three regions of Moldova were screened by ELISA and nested PCR. Of these cattle, 14 which were PCR positive, and these were molecularly characterized based on the nucleotide sequence of the env gene and the deduced amino acid sequence of the encoded gp51 protein...
February 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28213514/peripheral-membrane-interactions-boost-the-engagement-by-an-anti-hiv-1-broadly-neutralizing-antibody
#2
Edurne Rujas, José M M Caaveiro, Sara Insausti, Miguel García-Porras, Kouhei Tsumoto, José L Nieva
The 4E10 antibody displays an extreme breadth of HIV-1 neutralization and therefore constitutes a suitable model system for structure- guided vaccine design and immunotherapeutics against AIDS. In this regard, the relevance of auto- reactivity with membrane lipids for the biological function of this antibody is still a subject of controversy. To address this dispute, herein we have compared the membrane-partitioning ability of the 4E10 antibody and several of its variants, which were mutated at the region of the paratope surface in contact with the membrane-interface...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28212984/hiv-1-vpr-disrupts-mitochondria-axonal-transport-and-accelerates-neuronal-aging
#3
Ying Wang, Maryline Santerre, Italo Tempera, Kayla Martin, Ruma Mukerjee, Bassel E Sawaya
Disruption of mitochondria axonal transport, essential for the maintenance of synaptic and neuronal integrity and function, has been identified in neurodegenerative diseases. Whether HIV-1 viral proteins affect mitochondria axonal transport is unknown, albeit HIV-associated neurocognitive disorders occur in around half of the patients living with HIV. Therefore, we sought to examine the effect of HIV-1 viral protein R (Vpr) on mitochondria axonal transport. Using mice primary neuronal cultures, we demonstrated that 4-day Vpr treatment reduced the ratio of moving mitochondria associated with (i) less energy (ATP) supply, (ii) reduction in Miro-1 and (iii) increase of α-synuclein which led to loss of microtubule stability as demonstrated by inconsecutive distribution of acetylated α-tubulin along the axons...
February 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28211951/semiparametric-regression-analysis-of-interval-censored-competing-risks-data
#4
Lu Mao, Dan-Yu Lin, Donglin Zeng
Interval-censored competing risks data arise when each study subject may experience an event or failure from one of several causes and the failure time is not observed directly but rather is known to lie in an interval between two examinations. We formulate the effects of possibly time-varying (external) covariates on the cumulative incidence or sub-distribution function of competing risks (i.e., the marginal probability of failure from a specific cause) through a broad class of semiparametric regression models that captures both proportional and non-proportional hazards structures for the sub-distribution...
February 17, 2017: Biometrics
https://www.readbyqxmd.com/read/28211087/semiparametric-pseudoscore-for-regression-with-multidimensional-but-incompletely-observed-regressor
#5
Zonghui Hu, Jing Qin, Dean Follmann
We study the regression fβ (Y|X,Z), where Y is the response, Z∈Rd is a vector of fully observed regressors and X is the regressor with incomplete observation. To handle missing data, maximum likelihood estimation via expectation-maximisation (EM) is the most efficient but is sensitive to the specification of the distribution of X. Under a missing at random assumption, we propose an EM-type estimation via a semiparametric pseudoscore. Like in EM, we derive the conditional expectation of the score function given Y and Z, or the mean score, over the incompletely observed units under a postulated distribution of X...
February 16, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28209172/evaluation-of-the-contribution-of-the-transmembrane-region-to-the-ectodomain-conformation-of-the-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein
#6
Hanh T Nguyen, Navid Madani, Haitao Ding, Emerald Elder, Amy Princiotto, Christopher Gu, Patrice Darby, James Alin, Alon Herschhorn, John C Kappes, Youdong Mao, Joseph G Sodroski
BACKGROUND: The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env), a Type 1 transmembrane protein, assembles into a trimeric spike complex that mediates virus entry into host cells. The high potential energy of the metastable, unliganded Env trimer is maintained by multiple non-covalent contacts among the gp120 exterior and gp41 transmembrane Env subunits. Structural studies suggest that the gp41 transmembrane region forms a left-handed coiled coil that contributes to the Env trimer interprotomer contacts...
February 16, 2017: Virology Journal
https://www.readbyqxmd.com/read/28207902/methamphetamine-treatment-outcomes-among-gay-men-attending-a-lgbti-specific-treatment-service-in-sydney-australia
#7
Toby Lea, Johann Kolstee, Sarah Lambert, Ross Ness, Siobhan Hannan, Martin Holt
Gay and bisexual men (GBM) report higher rates of methamphetamine use compared to heterosexual men, and thus have a heightened risk of developing problems from their use. We examined treatment outcomes among GBM clients receiving outpatient counseling at a lesbian, gay, bisexual, transgender and intersex (LGBTI)-specific, harm reduction treatment service in Sydney, Australia. GBM receiving treatment for methamphetamine use from ACON's Substance Support Service between 2012-15 (n = 101) were interviewed at treatment commencement, and after 4 sessions (n = 60; follow-up 1) and 8 sessions (n = 32; follow-up 2)...
2017: PloS One
https://www.readbyqxmd.com/read/28207491/intrastructural-help-improving-the-hiv-1-envelope-antibody-response-induced-by-virus-like-particle-vaccines
#8
Vladimir Temchura, Klaus Überla
PURPOSE OF REVIEW: The importance of IgG Fc-effector functions for the efficacy of HIV vaccines is increasingly recognized. Although different types of vaccines were shown to induce antibodies with different Fc-activities, there is no clear strategy how to raise antibody responses with a desired pattern of Fc-effector functions. Given the central role of T-helper cells in regulating the germinal center reaction and the differentiation of B cells in an antigen-specific manner, the review will discuss whether T-helper cells directed against non-HIV envelope (Env) antigens could be harnessed to improve the HIV-Env antibody response...
February 14, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28207276/hydrophobic-nanoparticles-reduce-the-%C3%AE-sheet-content-of-sevi-amyloid-fibrils-and-inhibit-sevi-enhanced-hiv-infectivity
#9
Daniel A Sheik, Jeffrey M Chamberlain, Lauren R Brooks, Melissa L Clark, Young Hun Kim, Geoffray Leriche, Clifford P Kubiak, Stephen Dewhurst, Jerry Yang
Semen-Derived Enhancer of Virus Infection (SEVI) fibrils are naturally abundant amyloid aggregates found in semen that facilitate viral attachment and internalization of HIV in cells, thereby increasing the probability of infection. Mature SEVI fibrils are comprised of aggregated peptides exhibiting high β-sheet secondary structural characteristics. Herein, we show that polymers containing hydrophobic side chains can interact with SEVI and reduce its β-sheet content by ~45% compared to the β-sheet content of SEVI in the presence of polymers with hydrophilic side chains, as estimated by Polarization Modulation-Infrared Reflectance Absorption Spectroscopy Measurements...
February 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28205255/effect-of-postnatal-hiv-treatment-on-clinical-mastitis-and-breast-inflammation-in-hiv-infected-breast-feeding-women
#10
Sabrina Zadrozny, Daniel Westreich, Michael G Hudgens, Charles Chasela, Denise J Jamieson, Francis Martinson, Chifundo Zimba, Gerald Tegha, Irving Hoffman, William C Miller, Brian W Pence, Caroline C King, Athena P Kourtis, Wezi Msungama, Charles van der Horst
BACKGROUND: The relationship between mastitis and antiretroviral therapy among HIV-positive, breast-feeding women is unclear. METHODS: In the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, conducted in Lilongwe, Malawi, 2369 mother-infant pairs were randomized to a nutritional supplement group and to one of three treatment groups: maternal antiretroviral therapy (ART), infant nevirapine (NVP) or standard of care for 24 weeks of exclusive breast-feeding and 4 weeks of weaning...
February 16, 2017: Paediatric and Perinatal Epidemiology
https://www.readbyqxmd.com/read/28203694/frailty-and-physical-function-in-older-hiv-infected-adults
#11
Fatima Brañas, Zaida Jiménez, Matilde Sánchez-Conde, Fernando Dronda, Juan Carlos López-Bernaldo De Quirós, María J Pérez-Elías, Pilar Miralles, Margarita Ramírez, Ana Moreno, Juan Berenguer, Santiago Moreno
No abstract text is available yet for this article.
February 14, 2017: Age and Ageing
https://www.readbyqxmd.com/read/28203239/sublingual-priming-with-a-hiv-gp41-based-subunit-vaccine-elicits-mucosal-antibodies-and-persistent-b-memory-responses-in-non-human-primates
#12
Selma Bekri, Pierre Bourdely, Carmelo Luci, Nathalie Dereuddre-Bosquet, Bin Su, Frédéric Martinon, Véronique M Braud, Irene Luque, Pedro L Mateo, Sara Crespillo, Francisco Conejero-Lara, Christiane Moog, Roger Le Grand, Fabienne Anjuère
Persistent B cell responses in mucosal tissues are crucial to control infection against sexually transmitted pathogens like human immunodeficiency virus 1 (HIV-1). The genital tract is a major site of infection by HIV. Sublingual (SL) immunization in mice was previously shown to generate HIV-specific B cell immunity that disseminates to the genital tract. We report here the immunogenicity in female cynomolgus macaques of a SL vaccine based on a modified gp41 polypeptide coupled to the cholera toxin B subunit designed to expose hidden epitopes and to improve mucosal retention...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28202771/delayed-differentiation-of-potent-effector-cd8-t-cells-reducing-viremia-and-reservoir-seeding-in-acute-hiv-infection
#13
Hiroshi Takata, Supranee Buranapraditkun, Cari Kessing, James L K Fletcher, Roshell Muir, Virginie Tardif, Pearline Cartwright, Claire Vandergeeten, Wendy Bakeman, Carmen N Nichols, Suteeraporn Pinyakorn, Pokrath Hansasuta, Eugene Kroon, Thep Chalermchai, Robert O'Connell, Jerome Kim, Nittaya Phanuphak, Merlin L Robb, Nelson L Michael, Nicolas Chomont, Elias K Haddad, Jintanat Ananworanich, Lydie Trautmann
CD8(+) T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8(+) T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8(+) T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8(+) T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI)...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28202766/inhibition-of-hiv-1-maturation-via-small-molecule-targeting-of-the-amino-terminal-domain-in-the-viral-capsid-protein
#14
Weifeng Wang, Jing Zhou, Upul D Halambage, Kellie A Jurado, Augusta V Jamin, Yujie Wang, Alan N Engelman, Christopher Aiken
The HIV-1 capsid protein is an attractive therapeutic target owing to its multifunctionality in virus replication and the high fitness cost of amino acid substitutions in capsid to HIV-1 infectivity. To date, small molecule inhibitors have been identified that inhibit HIV-1 capsid assembly and/or impair its function in target cells. Here we describe the mechanism of action of the previously reported capsid-targeting HIV-1 inhibitor, BI compound 1 (C1). We show that C1 acts during HIV-1 maturation to prevent assembly of a mature viral capsid...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202763/inhibition-of-vpx-mediated-samhd1-and-vpr-mediated-hltf-degradation-by-selective-disruption-of-viral-crl4-dcaf1-e3-ubiquitin-ligase-assembly
#15
Hong Wang, Haoran Guo, Jiaming Su, Yajuan Rui, Wenwen Zheng, Wenying Gao, Wenyan Zhang, Zhaolong Li, Guanchen Liu, Wei Wei, Xiao-Fang Yu
The lentiviral accessory proteins Vpx and Vpr are known to utilize CRL4 (DCAF1) E3 ligase to induce the degradation of the host restriction factor SAMHD1 or transcriptional factor HLTF, respectively. Selective disruption of viral CRL4 (DCAF1) E3 ligase could be a promising antiviral strategy. Recently, we have determined that post-translational modification (neddylation) of Cullin-4 is required for the activation of Vpx-CRL4 (DCAF1) E3 ligase. However, the mechanism of Vpx/Vpr-CRL4 (DCAF1) E3 ligase assembly is still poorly understood...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202762/maternal-binding-and-neutralizing-igg-responses-targeting-the-c-terminal-region-of-the-v3-loop-are-predictive-of-reduced-peripartum-hiv-1-transmission-risk
#16
David R Martinez, Nathan Vandergrift, Ayooluwa O Douglas, Erin McGuire, John Bainbridge, Nathan I Nicely, David C Montefiori, Georgia D Tomaras, Genevieve G Fouda, Sallie R Permar
The development of an effective maternal HIV-1 vaccine that could synergize with antiretroviral therapy (ART) to eliminate pediatric HIV-1 infection will require the characterization of maternal immune responses capable of blocking transmission of autologous HIV viruses to the infant. We previously identified that maternal plasma antibody binding to linear epitopes within the variable loop 3 (V3) region of HIV envelope (Env) and neutralizing responses against easy to neutralize tier 1 viruses were associated with reduced risk of peripartum HIV infection in the historic U...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202751/superiority-in-rhesus-macaques-of-targeting-hiv-1-env-gp140-to-cd40-versus-lox-1-in-combination-with-replication-competent-nyvac-kc-for-induction-of-env-specific-antibody-and-t-cell-responses
#17
Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D Tomaras, David C Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E Foulds, Shing-Fen Kao, Xuesong Yu, Alicia Sato, Nicole L Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres Salazar, Steve Self, Jimmy Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy
We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P =0...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202615/il-13-mediated-regulation-of-learning-and-memory
#18
Tiroyaone M Brombacher, Justin K Nono, Keisha S De Gouveia, Nokuthula Makena, Matthew Darby, Jacqueline Womersley, Ousman Tamgue, Frank Brombacher
The role of proinflammatory cytokines in cognitive function has been investigated with both beneficial and possible detrimental effects, depending on the cytokine. More recently, the type 2 IL-4 has been demonstrated to play a role in cognition. In this study, using the Morris water maze task, we demonstrate that IL-13-deficient mice are significantly impaired in working memory as well as attenuated reference memory, both functions essential for effective complex learning. During the learning process, wild-type mice increased the number of CD4(+) T cells in the meninges and production of IL-13, whereas neither Morris water maze-trained IL-4 nor trained IL-13-deficient mice were able to increase CD4(+) T cells in the meninges...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28198713/cd1d-restricted-natural-killer-t-cells-are-preserved-in-indian-long-term-non-progressors-ltnps
#19
Dharmendra Singh, Manisha Ghate, Sheela Godbole, Smita Kulkarni, Madhuri Thakar
BACKGROUND: Natural killer T (NKT) cells act as a bridge between innate and adaptive immune responses. Limited information is available regarding the role of NKT cells in the HIV disease progression especially HIV-1 C infection. METHODOLOGY: NKT cells were characterized for their frequency and the activation, aging, exhaustion status and their proliferation ability in 32 long term non progressors (LTNPs), 40 progressors, 18 patients before and after suppressive cART along with 35 HIV-1 negative subjects using multicolor flowcytometry...
February 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28196864/mechanistic-understanding-of-n-glycosylation-in-ebola-virus-glycoprotein-maturation-and-function
#20
Bin Wang, Yujie Wang, Dylan A Frabutt, Xihe Zhang, Xiaoyu Yao, Dan Hu, Zhuo Zhang, Chaonan Liu, Shimin Zheng, Shi-Hua Xiang, Yong-Hui Zheng
The Ebola virus (EBOV) trimeric envelope glycoprotein (GP) precursors are cleaved into the receptor-binding GP1 and the fusion-mediating GP2 subunits and incorporated into virions to initiate infection. GP1 and GP2 form heterodimers, which have 15 or 2 N-glycosylation sites (NGSs), respectively. Here, we investigated the mechanism of how N-glycosylation contributes to GP expression, maturation, and function. As reported before, we found that although GP1 NGSs are not critical, the two GP2 NGSs, N563 and N618, are essential to the GP function...
February 14, 2017: Journal of Biological Chemistry
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