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HIV mutant

Rafael Conceição de Souza, Gabriela de Medeiros Muniz, Andrei Santos Siqueira, Adonis de Melo Lima, Alessandra Pereira da Silva, Evonnildo Costa Gonçalves, João Lídio da Silva Gonçalves Vianez Júnior
Human immunodeficiency virus (HIV) infections continue to exert an enormous impact on global human health. This led experts to emphasize the importance of new measures for preventing HIV infections, including the development of vaccines and novel drugs. In this context, a promising approach involves the use of lectins that can bind the surface envelope glycoprotein gp120 of HIV with high affinity, preventing viral entry. The cyanobacterial lectin microvirin (MVN) has been proposed as a candidate for development as a topical microbicide because of its ability to bind to high mannose-type glycans, potently inhibiting HIV-1 entry...
November 2016: Journal of Molecular Modeling
Yusuke Matsui, Keisuke Shindo, Kayoko Nagata, Noriyoshi Yoshinaga, Kotaro Shirakawa, Masayuki Kobayashi, Akifumi Takaori-Kondo
HIV type 1 overcomes the host restriction factor apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) proteins by organizing an E3 ubiquitin ligase complex together with viral infectivity factor (Vif) and a host transcription cofactor core binding factor β (CBFβ ). CBFβ is essential for Vif to counteract APOBEC3 by enabling the recruitment of cullin 5 to the complex and increasing steady-state level of Vif protein, however, the mechanisms by which CBFβ up-regulates Vif protein remains unclear...
October 7, 2016: Journal of Biological Chemistry
François E Dufrasne, Catherine Lombard, Patrick Goubau, Jean Ruelle
BST-2 or tetherin is a host cell restriction factor that prevents the budding of enveloped viruses at the cell surface, thus impairing the viral spread. Several countermeasures to evade this antiviral factor have been positively selected in retroviruses: the human immunodeficiency virus type 2 (HIV-2) relies on the envelope glycoprotein (Env) to overcome BST-2 restriction. The Env gp36 ectodomain seems involved in this anti-tetherin activity, however residues and regions interacting with BST-2 are not clearly defined...
October 14, 2016: Viruses
Xiao Li, Ping Gao, Boshi Huang, Zhongxia Zhou, Zhao Yu, Zheng Yuan, Huiqing Liu, Christophe Pannecouque, Dirk Daelemans, Erik De Clercq, Peng Zhan, Xinyong Liu
To further explore the chemical space around the entrance channel of HIV-1 reverse transcriptase (RT), a series of novel indolylarylsulfones (IASs) bearing N-substituted piperidine at indole-2-carboxamide were identified as potent HIV NNRTIs by structure-guided scaffold morphing and fragment rearrangement. All the IASs exhibited moderate to excellent potency against wild-type HIV-1 with EC50 values ranging from 0.62 μM to 0.006 μM 8 (EC50 = 6 nM) and 18 (EC50 = 9 nM) were identified as the most potent compounds, which were more active than NVP and DLV, and reached the same order of EFV and ETV...
October 5, 2016: European Journal of Medicinal Chemistry
Merlin L Robb, Jintanat Ananworanich
PURPOSE OF REVIEW: Understanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption). RECENT FINDINGS: The AHI period is brief and peak viremia predicts a viral set point that occurs 4-5 weeks following infection...
September 29, 2016: Current Opinion in HIV and AIDS
Yangdong Sun, Qiao Ye, Min Wu, Yonghong Wu, Chenggang Zhang, Weiqun Yan
This study aimed to validate the high yield and soluble expression of proteins carrying the transactivator of transcription (Tat) peptide tag, and further explored the potential mechanism by which the Tat tag increases expression. Escherichia coli superoxide dismutase (SOD) proteins, including SodA, SodB and SodC, were selected for analysis. As expected, the yields and the solubility of Tat-tagged proteins were higher than those of Tat-free proteins, and similar results were observed for the total SOD enzyme activity...
October 14, 2016: Experimental & Molecular Medicine
Mahmoud Mohammad Yaseen, Mohammad Mahmoud Yaseen, Mohammad Ali Alqudah
Although available antiretroviral therapy (ART) has changed human immunodeficiency virus (HIV)-1 infection to a non-fatal chronic disease, the economic burden of lifelong therapy, severe adverse ART effects, daily ART adherence, and emergence of ART-resistant HIV-1 mutants require prospecting for alternative therapeutic modalities. Indeed, a growing body of evidence suggests that broadly neutralizing anti-HIV-1 antibodies (BNAbs) may offer one such feasible alternative. To evaluate their therapeutic potential in established HIV-1 infection, we sought to address recent advances in pre-clinical and clinical investigations in this area of HIV-1 research...
October 14, 2016: International Reviews of Immunology
Ting Yuan, Weitong Yao, Kenzo Tokunaga, Rongge Yang, Binlian Sun
BACKGROUND: Several members of the TRIM family have been implicated in antiviral defense. Our previous report showed that human TRIM11 potently inhibited HIV-1 transduction by reducing the viral reverse transcripts. These results prompted us to examine the effect of TRIM11 on HIV-1 uncoating, which is closely related to viral reverse transcription. RESULTS: Using a combination of in vitro binding and in situ proximity ligation assay, we showed that TRIM11 could interact with HIV-1 capsid...
October 13, 2016: Retrovirology
Tomáš Kroupa, Hana Langerová, Michal Doležal, Jan Prchal, Vojtěch Spiwok, Eric Hunter, Michaela Rumlová, Richard Hrabal, Tomáš Ruml
Matrix proteins play a key role in the transport of retroviral proteins inside infected cells and in the interaction with cellular membranes. In most retroviruses, retroviral matrix proteins are N-terminally myristoylated. This modification serves as a membrane targeting signal and also as an anchor for the membrane interaction. The aim of this work was to characterize interactions anchoring retroviral matrix protein at the plasma membrane of infected cell. To address this issue, we compared the structures and membrane affinity of the Mason-Pfizer monkey virus (M-PMV) wild-type matrix protein with its two budding deficient double mutants, i...
October 7, 2016: Journal of Molecular Biology
Bilal Nizami, Dominique Sydow, Gerhard Wolber, Bahareh Honarparvar
Regardless of advances in anti-HIV therapy, HIV infection remains an immense challenge due to the rapid onset of mutation instigating drug resistance. Rilpivirine is a second generation di-aryl pyrimidine (DAPY) derivative, known to effectively inhibit wild-type (WT) as well as various mutant HIV-1 reverse transcriptase (RT). In this study, a cumulative 240 ns of molecular dynamic (MD) simulations of WT HIV-1 RT and its corresponding K103N mutated form, complexed with rilpivirine, were performed in solution...
September 9, 2016: Molecular BioSystems
Merlin L Robb, Jintanat Ananworanich
PURPOSE OF REVIEW: Understanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption). RECENT FINDINGS: The AHI period is brief and peak viremia predicts a viral set point that occurs 4-5 weeks following infection...
November 2016: Current Opinion in HIV and AIDS
Wiyada Dankai, Monsicha Pongpom, Sirida Youngchim, Chester R Cooper, Nongnuch Vanittanakom
Talaromyces marneffei, formerly Penicillium marneffei, is a thermally dimorphic fungus. It causes a fatal disseminated disease in patients infected with the human immunodeficiency virus (HIV). Studies on the stress defense mechanism of T. marneffei can lead to a better understanding of the pathogenicity and the progression of the disease due to this fungus. The basic leucine-zipper (bZip) transcription factor gene in Saccharomyces cerevisiae, named yap1 (yeast activating protein-1), is known as a crucial central regulator of stress responses including those caused by oxidative agents, cadmium, and drugs...
2016: PloS One
Dennis C Liotta, George R Painter
The HIV/AIDS epidemic, which was first reported on in 1981, progressed in just 10 years to a disease afflicting 10 million people worldwide including 1 million in the US. In 1987, AZT was approved for treating HIV/AIDS. Unfortunately, its clinical usefullness was severly limited by associated toxicities and the emergence of resistance. Three other drugs that were approved in the early 1990s suffered from similar liabilities. In 1990, the Liotta group at Emory University developed a highly diastereoselective synthesis of racemic 3'-thia-2',3'-dideoxycytidine and 3'-thia-2',3'-5-fluorodideoxycytidine and demonstrated that these compounds exhibited excellent anti-HIV activity with no apparent cytotoxicity...
October 5, 2016: Accounts of Chemical Research
Janani Varadarajan, Mary Jane McWilliams, Bryan T Mott, Craig J Thomas, Steven J Smith, Stephen H Hughes
BACKGROUND: HIV-1 integrase is the target for three FDA-approved drugs, raltegravir, elvitegravir, and dolutegravir. All three drugs bind at the active site of integrase and block the strand transfer step of integration. We previously showed that sub-optimal doses of the anti-HIV drug raltegravir can cause aberrant HIV integrations that are accompanied by a variety of deletions, duplications, insertions and inversions of the adjacent host sequences. RESULTS: We show here that a second drug, elvitegravir, also causes similar aberrant integrations...
September 29, 2016: Retrovirology
Birthe Trautz, Virginia Pierini, Rebecka Wombacher, Bettina Stolp, Amanda J Chase, Massimo Pizzato, Oliver T Fackler
: SERINC 3 and 5 are recently identified host cell inhibitors of HIV-1 particle infectivity that are counteracted by the viral pathogenesis factor Nef. Here we confirm that HIV-1 Nef, but not HIV-1 Vpu, antagonizes the particle infectivity restriction of SERINC5. SERINC5 antagonism occurred in parallel to other Nef activities including cell surface receptor downregulation, trans-Golgi-network targeting of Lck and inhibition of host cell actin dynamics. Interaction motifs with host cell endocytic machinery, Nef-associated kinase complex as well as CD4 cytoplasmic tail/HIV-1 protease were identified as essential Nef determinants for SERINC5 antagonism...
September 28, 2016: Journal of Virology
Muntasir Alam, Takeo Kuwata, Kazuya Shimura, Masaru Yokoyama, Kristel Paola Ramirez Valdez, Kazuki Tanaka, Yasuhiro Maruta, Shinya Oishi, Nobutaka Fujii, Hironori Sato, Masao Matsuoka, Shuzo Matsushita
BACKGROUND: HIV-1 typically develops resistance to any single antiretroviral agent. Combined anti-retroviral therapy to reduce drug-resistance development is necessary to control HIV-1 infection. Here, to assess the utility of a combination of antibody and fusion inhibitor treatments, we investigated the potency of monoclonal antibodies at neutralizing HIV-1 variants that are resistant to fusion inhibitors. RESULTS: Mutations that confer resistance to four fusion inhibitors, enfuvirtide, C34, SC34, and SC34EK, were introduced into the envelope of HIV-1JR-FL, a CCR5-tropic tier 2 strain...
September 27, 2016: Retrovirology
Ming-Tain Lai, Vandna Munshi, Meiqing Lu, MeiZhen Feng, Renee Hrin-Solt, Philip M McKenna, Daria J Hazuda, Michael D Miller
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a mainstay of therapy for human immunodeficiency type 1 virus (HIV-1) infections. However, their effectiveness can be hampered by the emergence of resistant mutations. To aid in designing effective NNRTIs against the resistant mutants, it is important to understand the resistance mechanism of the mutations. Here, we investigate the mechanism of the two most prevalent NNRTI-associated mutations with K103N or Y181C substitution. Virus and reverse transcriptase (RT) with K103N/Y188F, K103A, or K103E substitutions and with Y181F, Y188F, or Y181F/Y188F substitutions were employed to study the resistance mechanism of the K103N and Y181C mutants, respectively...
2016: Viruses
Xiaojun Xu, Shi-Jie Chen
RNA/RNA interactions are essential for genomic RNA dimerization and regulation of gene expression. Intermolecular loop-loop base pairing is a widespread and functionally important tertiary structure motif in RNA machinery. However, computational prediction of intermolecular loop-loop base pairing is challenged by the entropy and free energy calculation due to the conformational constraint and the intermolecular interactions. In this chapter, we describe a recently developed statistical mechanics-based method for the prediction of RNA/RNA complex structures and stabilities...
2016: Methods in Molecular Biology
Nopporn Chutiwitoonchai, Lowela Siarot, Eri Takeda, Tatsuo Shioda, Motoki Ueda, Yoko Aida
HIV-1 budding requires interaction between Gag and cellular TSG101 to initiate viral particle assembly and release via the endosomal sorting complexes required for transport (ESCRT) pathway. However, some reports show that overexpression of TSG101 inhibits virus release by disruption of Gag targeting process. Since a HIV-1 accessory protein, Vpr binds to Gag p6 domain at the position close to the binding site for TSG101, whether Vpr implicates TSG101 overexpression effect has not been investigated. Here, we found that Vpr abrogates TSG101 overexpression effect to rescue viral production...
2016: PloS One
Fredrick Kateera, Sam L Nsobya, Steven Tukwasibwe, Emmanuel Hakizimana, Leon Mutesa, Petra F Mens, Martin P Grobusch, Michèle van Vugt, Nirbhay Kumar
Faced with intense levels of chloroquine (CQ) resistance in Plasmodium falciparum malaria, Rwanda replaced CQ with amodiaquine (AQ)+sulfadoxine-pyrimethamine (SP) in 2001, and subsequently with artemether-lumefantrine (AL) in 2006, as first-line treatments for uncomplicated malaria. Following years of discontinuation of CQ use, re-emergence of CQ-susceptible parasites has been reported in countries including Malawi, Kenya and Tanzania. In contrast, high levels of SP resistant mutant parasites continue to be reported even in countries of presumed reduced SP drug selection pressure...
September 17, 2016: Acta Tropica
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