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Retrovirology

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https://www.readbyqxmd.com/read/27905985/tlr7-8-agonist-induces-a-post-entry-samhd1-independent-block-to-hiv-1-infection-of-monocytes
#1
Henning Hofmann, Bénédicte Vanwalscappel, Nicolin Bloch, Nathaniel R Landau
BACKGROUND: Monocytes, the primary myeloid cell-type in peripheral blood, are resistant to HIV-1 infection as a result of the lentiviral restriction factor SAMHD1. Toll-like receptors recognize microbial pathogen components, inducing the expression of antiviral host proteins and proinflammatory cytokines. TLR agonists that mimic microbial ligands have been found to have activity against HIV-1 in macrophages. The induction of restriction factors in monocytes by TLR agonist activation has not been well studied...
December 1, 2016: Retrovirology
https://www.readbyqxmd.com/read/27894306/first-phase-i-human-clinical-trial-of-a-killed-whole-hiv-1-vaccine-demonstration-of-its-safety-and-enhancement-of-anti-hiv-antibody-responses
#2
Eunsil Choi, Chad J Michalski, Seung Ho Choo, Gyoung Nyoun Kim, Elizabeth Banasikowska, Sangkyun Lee, Kunyu Wu, Hwa-Yong An, Anthony Mills, Stefan Schneider, U Fritz Bredeek, Daniel R Coulston, Shilei Ding, Andrés Finzi, Meijuan Tian, Katja Klein, Eric J Arts, Jamie F S Mann, Yong Gao, C Yong Kang
BACKGROUND: Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus...
November 28, 2016: Retrovirology
https://www.readbyqxmd.com/read/27871328/membrane-bound-modified-form-of-clade-b-env-jrcsf-is-suitable-for-immunogen-design-as-it-is-efficiently-cleaved-and-displays-all-the-broadly-neutralizing-epitopes-including-v2-and-c2-domain-dependent-conformational-epitopes
#3
Supratik Das, Saikat Boliar, Nivedita Mitra, Sweety Samal, Manish Bansal, Wayne C Koff, Bimal K Chakrabarti
BACKGROUND: Antigenicity of HIV-1 envelope proteins (Envs) of both lab-adapted and primary isolates expressed on the cell surface rarely match with in vitro neutralization of viruses, pseudo-typed with corresponding Envs. Often, both neutralizing and non-neutralizing antibodies bind to Envs expressed on the cell membrane. This could be due to the lack of efficient cleavage of Env expressed on the cell surface. Naturally occurring, efficiently cleaved Envs with appropriate antigenic properties are relatively rare...
November 21, 2016: Retrovirology
https://www.readbyqxmd.com/read/27846847/hiv-and-zika-when-will-we-be-able-to-end-these-epidemics
#4
EDITORIAL
Mark A Wainberg, Andrew M L Lever
No abstract text is available yet for this article.
November 15, 2016: Retrovirology
https://www.readbyqxmd.com/read/27835956/sl1-revisited-functional-analysis-of-the-structure-and-conformation-of-hiv-1-genome-rna
#5
Sayuri Sakuragi, Masaru Yokoyama, Tatsuo Shioda, Hironori Sato, Jun-Ichi Sakuragi
BACKGROUND: The dimer initiation site/dimer linkage sequence (DIS/DLS) region of HIV is located on the 5' end of the viral genome and suggested to form complex secondary/tertiary structures. Within this structure, stem-loop 1 (SL1) is believed to be most important and an essential key to dimerization, since the sequence and predicted secondary structure of SL1 are highly stable and conserved among various virus subtypes. In particular, a six-base palindromic sequence is always present at the hairpin loop of SL1 and the formation of kissing-loop structure at this position between the two strands of genomic RNA is suggested to trigger dimerization...
November 11, 2016: Retrovirology
https://www.readbyqxmd.com/read/27821119/insufficient-natural-killer-cell-responses-against-retroviruses-how-to-improve-nk-cell-killing-of-retrovirus-infected-cells
#6
REVIEW
Elisabeth Littwitz-Salomon, Ulf Dittmer, Kathrin Sutter
Natural killer (NK) cells belong to the innate immune system and protect against cancers and a variety of viruses including retroviruses by killing transformed or infected cells. They express activating and inhibitory receptors on their cell surface and often become activated after recognizing virus-infected cells. They have diverse antiviral effector functions like the release of cytotoxic granules, cytokine production and antibody dependent cellular cytotoxicity. The importance of NK cell activity in retroviral infections became evident due to the discovery of several viral strategies to escape recognition and elimination by NK cells...
November 8, 2016: Retrovirology
https://www.readbyqxmd.com/read/27814766/antibody-dependent-cd56-t-cell-responses-are-functionally-impaired-in-long-term-hiv-1-infection
#7
Xueying Fan, Liyan Zhu, Hua Liang, Zhe Xie, Xiangbo Huang, Shuo Wang, Tao Shen
BACKGROUND: Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in slowing human immunodeficiency virus type-1 (HIV-1) disease progression and protecting from HIV-1 infection. Besides classic NK cells, CD56+ T cells also have some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. However, little is known about the potentials of antibody-dependent CD56+ T cell responses and the association between antibody-dependent CD56+ T cell responses and HIV-1 disease progression...
November 4, 2016: Retrovirology
https://www.readbyqxmd.com/read/27814725/whole-genome-sequencing-of-51-breast-cancers-reveals-that-tumors-are-devoid-of-bovine-leukemia-virus-dna
#8
Nicolas A Gillet, Luc Willems
Controversy exists regarding the association of bovine leukemia virus (BLV) and breast cancer. PCR-based experimental evidence indicates that BLV DNA is present in breast tissue and that as many as 37% of cancer cases may be attributable to viral exposure. Since this association might have major consequences for human health, we evaluated 51 whole genomes of breast cancer samples for the presence of BLV DNA. Among 32 billion sequencing reads retrieved from the NCBI database of genotype and phenotype, none mapped on different strains of the BLV genome...
November 4, 2016: Retrovirology
https://www.readbyqxmd.com/read/27809912/frequency-and-env-determinants-of-hiv-1-subtype-c-strains-from-antiretroviral-therapy-naive-subjects-that-display-incomplete-inhibition-by-maraviroc
#9
Katharina Borm, Martin R Jakobsen, Kieran Cashin, Jacqueline K Flynn, Paula Ellenberg, Lars Ostergaard, Benhur Lee, Melissa J Churchill, Michael Roche, Paul R Gorry
BACKGROUND: Entry of human immunodeficiency virus type 1 (HIV-1) into cells involves the interaction of the viral gp120 envelope glycoproteins (Env) with cellular CD4 and a secondary coreceptor, which is typically one of the chemokine receptors CCR5 or CXCR4. CCR5-using (R5) HIV-1 strains that display reduced sensitivity to CCR5 antagonists can use antagonist-bound CCR5 for entry. In this study, we investigated whether naturally occurring gp120 alterations in HIV-1 subtype C (C-HIV) variants exist in antiretroviral therapy (ART)-naïve subjects that may influence their sensitivity to the CCR5 antagonist maraviroc (MVC)...
November 3, 2016: Retrovirology
https://www.readbyqxmd.com/read/27760548/atl-derived-exosomes-modulate-mesenchymal-stem-cells-potential-role-in-leukemia-progression
#10
Jamal El-Saghir, Farah Nassar, Nadim Tawil, Marwan El-Sabban
BACKGROUND: Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Exosomes can potentially transfer their cargo to other cells, implicating them in many patho-physiological processes. Mesenchymal stem cells (MSCs), residents of the bone marrow and metastatic niches, potentially interact with cancer cells and/or their derived exosomes. In this study, we investigated whether exosomes derived from adult T-cell leukemia/lymphoma (ATL) cells act as intercellular messengers delivering leukemia-related genes that modulate the properties of human MSCs in favor of leukemia...
October 19, 2016: Retrovirology
https://www.readbyqxmd.com/read/27737691/an-hiv-1-capsid-binding-protein-trim11-accelerates-viral-uncoating
#11
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
https://www.readbyqxmd.com/read/27682062/drug-resistant-integrase-mutants-cause-aberrant-hiv-integrations
#12
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
https://www.readbyqxmd.com/read/27670680/enhanced-antibody-mediated-neutralization-of-hiv-1-variants-that-are-resistant-to-fusion-inhibitors
#13
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
https://www.readbyqxmd.com/read/27377064/retrovirus-integration-database-rid-a-public-database-for-retroviral-insertion-sites-into-host-genomes
#14
Wei Shao, Jigui Shan, Mary F Kearney, Xiaolin Wu, Frank Maldarelli, John W Mellors, Brian Luke, John M Coffin, Stephen H Hughes
UNLABELLED: The NCI Retrovirus Integration Database is a MySql-based relational database created for storing and retrieving comprehensive information about retroviral integration sites, primarily, but not exclusively, HIV-1. The database is accessible to the public for submission or extraction of data originating from experiments aimed at collecting information related to retroviral integration sites including: the site of integration into the host genome, the virus family and subtype, the origin of the sample, gene exons/introns associated with integration, and proviral orientation...
July 4, 2016: Retrovirology
https://www.readbyqxmd.com/read/27246201/molecular-clock-of-hiv-1-envelope-genes-under-early-immune-selection
#15
Sung Yong Park, Tanzy M T Love, Alan S Perelson, Wendy J Mack, Ha Youn Lee
BACKGROUND: The molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1's early evolution in the presence of immune selection has not yet been fully examined. RESULTS: We identified molecular clock signatures from 1587 previously published HIV-1 full envelope gene sequences obtained since acute infection in 15 subjects...
June 1, 2016: Retrovirology
https://www.readbyqxmd.com/read/27000403/the-interferon-induced-antiviral-protein-pml-trim19-promotes-the-restriction-and-transcriptional-silencing-of-lentiviruses-in-a-context-specific-isoform-specific-fashion
#16
Nasser Masroori, Natacha Merindol, Lionel Berthoux
BACKGROUND: The promyelocytic leukemia (PML) protein, a type I interferon (IFN-I)-induced gene product and a member of the tripartite motif (TRIM) family, modulates the transcriptional activity of viruses belonging to various families. Whether PML has an impact on the replication of HIV-1 has not been fully addressed, but recent studies point to its possible involvement in the restriction of HIV-1 in human cells and in the maintenance of transcriptional latency in human cell lines in which HIV-1 is constitutively repressed...
March 22, 2016: Retrovirology
https://www.readbyqxmd.com/read/26979152/analysis-of-the-mechanical-properties-of-wild-type-and-hyperstable-mutants-of-the-hiv-1-capsid
#17
Ruben Ramalho, Sanela Rankovic, Jing Zhou, Christopher Aiken, Itay Rousso
BACKGROUND: The human immunodeficiency virus (HIV-1) capsid is a self-assembled protein shell that contains the viral genome. During the stages between viral entry into a host cell and nuclear import of the viral DNA, the capsid dissociates in a process known as uncoating, which leads to the release of the viral genetic material. Mutations that alter the stability of the capsid affect the uncoating rate and impair HIV-1 infectivity. RESULTS: To gain further insight into the role of capsid stability during uncoating, we used atomic force spectroscopy to quantify the stiffness of the capsid...
March 15, 2016: Retrovirology
https://www.readbyqxmd.com/read/26852322/human-endogenous-retrovirus-herv-expression-is-not-induced-by-treatment-with-the-histone-deacetylase-hdac-inhibitors-in-cellular-models-of-hiv-1-latency
#18
Tara Hurst, Matthew Pace, Aris Katzourakis, Rodney Phillips, Paul Klenerman, John Frater, Gkikas Magiorkinis
BACKGROUND: While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells...
February 6, 2016: Retrovirology
https://www.readbyqxmd.com/read/26837192/mechanisms-of-escape-from-the-pgt128-family-of-anti-hiv-broadly-neutralizing-antibodies
#19
Stefanie A Krumm, Hajer Mohammed, Khoa M Le, Max Crispin, Terri Wrin, Pascal Poignard, Dennis R Burton, Katie J Doores
BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. The PGT125-131 bnAb family is of particular interest due to its superior breadth and potency. The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop...
February 2, 2016: Retrovirology
https://www.readbyqxmd.com/read/26767784/identification-and-spontaneous-immune-targeting-of-an-endogenous-retrovirus-k-envelope-protein-in-the-indian-rhesus-macaque-model-of-human-disease
#20
Helen L Wu, Enrique J Léon, Lyle T Wallace, Francesca A Nimiyongskul, Matthew B Buechler, Laura P Newman, Philip A Castrovinci, R Paul Johnson, Robert J Gifford, R Brad Jones, Jonah B Sacha
BACKGROUND: Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that have invaded the germ line of both humans and non-human primates. Most ERVs are functionally crippled by deletions, mutations, and hypermethylation, leading to the view that they are inert genomic fossils. However, some ERVs can produce mRNA transcripts, functional viral proteins, and even non-infectious virus particles during certain developmental and pathological processes. While there have been reports of ERV-specific immunity associated with ERV activity in humans, adaptive immune responses to ERV-encoded gene products remain poorly defined and have not been investigated in the physiologically relevant non-human primate model of human disease...
January 15, 2016: Retrovirology
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