1,512 results match your criteria Retrovirology[Journal]


Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir.

Retrovirology 2018 Dec 14;15(1):77. Epub 2018 Dec 14.

Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.

Background: HIV infection and antiretroviral treatment are associated with changes in lipid levels, insulin resistance and risk of cardiovascular disease (CVD). We investigated these changes in the first 96 weeks of treatment with low-dose stavudine or tenofovir regimens.

Methods: This is a secondary analysis of a double blind, randomised controlled trial performed in South-Africa, Uganda and India comparing low-dose stavudine (20 mg twice daily) with tenofovir in combination with efavirenz and lamivudine in antiretroviral-naïve adults (n = 1067) (Clinicaltrials. Read More

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December 2018

Reduction of inflammation and T cell activation after 6 months of cART initiation during acute, but not in early chronic HIV-1 infection.

Retrovirology 2018 Dec 12;15(1):76. Epub 2018 Dec 12.

Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz -IOC, FIOCRUZ, Av Brasil, 4365, Pavilhão Leônidas Deane, sala 401, Rio de Janeiro, 21040360, Brazil.

Objectives: To investigate the impact of early combined antiretroviral therapy (cART) on inflammation biomarkers and immune activation during acute and early chronic HIV-1 infection.

Methods: We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of inflammation biomarkers, CD8CD38HLA-DR T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Read More

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December 2018
1 Read

MBL2 gene polymorphisms in HHV-8 infection in people living with HIV/AIDS.

Retrovirology 2018 Nov 27;15(1):75. Epub 2018 Nov 27.

Virology Division, Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, 50670-901, Brazil.

Background: Host genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of MBL protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections. The aim of this study was to estimate the frequency of alleles, genotypes and haplotypes related to -550, -221 and exon 1 polymorphisms of the MBL2 gene and investigate their association with HHV-8 in people living with HIV/AIDS (PLWHA), as well as the impacts on CD4 cell count and HIV viral load in HIV/HHV-8 coinfected and HIV monoinfected patients.

Results: A cross sectional study in PLWHA, with and without HHV-8 infection, exploring associations between different factors, was performed in the outpatient infectious and parasitic diseases clinic at a referral hospital. Read More

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November 2018
2 Reads

HIV-1 immunogens and strategies to drive antibody responses towards neutralization breadth.

Retrovirology 2018 Nov 26;15(1):74. Epub 2018 Nov 26.

Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Location AMC, Meibergdreef 9, Room K3-105, 1105AZ, Amsterdam, The Netherlands.

Despite enormous efforts no HIV-1 vaccine has been developed that elicits broadly neutralizing antibodies (bNAbs) to protect against infection to date. The high antigenic diversity and dense N-linked glycan armor, which covers nearly the entire HIV-1 envelope protein (Env), are major roadblocks for the development of bNAbs by vaccination. In addition, the naive human antibody repertoire features a low frequency of exceptionally long heavy chain complementary determining regions (CDRH3s), which is a typical characteristic that many HIV-1 bNAbs use to penetrate the glycan armor. Read More

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November 2018
1 Read

Antibody-mediated prevention and treatment of HIV-1 infection.

Retrovirology 2018 Nov 16;15(1):73. Epub 2018 Nov 16.

Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Fürst-Pückler-Str. 56, 50935, Cologne, Germany.

Novel broadly neutralizing antibodies targeting HIV-1 hold promise for their use in the prevention and treatment of HIV-1 infection. Pre-clinical results have encouraged the evaluation of these antibodies in healthy and HIV-1-infected humans. In first clinical trials, highly potent broadly neutralizing antibodies have demonstrated their safety and significant antiviral activity by reducing viremia and delaying the time to viral rebound in individuals interrupting antiretroviral therapy. Read More

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November 2018
5 Reads

Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP.

Retrovirology 2018 Nov 6;15(1):72. Epub 2018 Nov 6.

Department of Microbiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan.

Background: Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, there is an association between HTLV-1 tax subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. To investigate the role of HTLV-1 subgroups in viral pathogenesis, we studied the functional difference in the subgroup-specific viral transcriptional regulators Tax and HBZ using microarray analysis, reporter gene assays, and evaluation of viral-host protein-protein interaction.

Results: (1) Transcriptional changes in Jurkat Tet-On human T-cells that express each subgroup of Tax or HBZ protein under the control of an inducible promoter revealed different target gene profiles; (2) the number of differentially regulated genes induced by HBZ was 2-3 times higher than that induced by Tax; (3) Tax and HBZ induced the expression of different classes of non-coding RNAs (ncRNAs); (4) the chemokine CXCL10, which has been proposed as a prognostic biomarker for HAM/TSP, was more efficiently induced by subgroup-A Tax (Tax-A) than subgroup-B Tax (Tax-B), in vitro as well as in unmanipulated (ex vivo) PBMCs obtained from HAM/TSP patients; (5) reporter gene assays indicated that although transient Tax expression in an HTLV-1-negative human T-cell line activated the CXCL10 gene promoter through the NF-κB pathway, there was no difference in the ability of each subgroup of Tax to activate the CXCL10 promoter; however, (6) chromatin immunoprecipitation assays showed that the ternary complex containing Tax-A is more efficiently recruited onto the promoter region of CXCL10, which contains two NF-κB binding sites, than that containing Tax-B. Read More

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November 2018
3 Reads

The role of integration and clonal expansion in HIV infection: live long and prosper.

Retrovirology 2018 Oct 23;15(1):71. Epub 2018 Oct 23.

HIV Dynamics and Replication Program, NCI, NIH, Frederick, MD, 21702, USA.

Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells with replication competent HIV proviruses form a reservoir that persists despite cART and such reservoirs are at the center of efforts to eradicate or control infection without cART. Read More

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October 2018
3 Reads

The expanding array of HIV broadly neutralizing antibodies.

Authors:
Laura E McCoy

Retrovirology 2018 Oct 16;15(1):70. Epub 2018 Oct 16.

Division of Infection and Immunity, University College London, London, UK.

A large array of broadly neutralizing antibodies (bnAbs) against HIV have been isolated and described, particularly in the last decade. This continually expanding array of bnAbs has crucially led to the identification of novel epitopes on the HIV envelope protein via which antibodies can block a broad range of HIV strains. Moreover, these studies have produced high-resolution understanding of these sites of vulnerability on the envelope protein. Read More

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October 2018
5 Reads

Host SAMHD1 protein restricts endogenous reverse transcription of HIV-1 in nondividing macrophages.

Retrovirology 2018 Oct 13;15(1):69. Epub 2018 Oct 13.

Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, 30322, USA.

Background: SAM domain and HD domain containing protein 1 (SAMHD1) is a host anti-HIV-1 restriction factor known to suppress viral reverse transcription in nondividing myeloid cells by its dNTP triphosphorylase activity that depletes cellular dNTPs. However, HIV-2 and some SIV strains rapidly replicate in macrophages due to their accessory protein, viral protein X (Vpx), which proteosomally degrades SAMHD1 and elevates dNTP levels. Endogenous reverse transcription (ERT) of retroviruses is the extra-cellular reverse transcription step that partially synthesizes proviral DNAs within cell-free viral particles before the viruses infect new cells. Read More

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October 2018
3 Reads

Friend retrovirus infection induces the development of memory-like natural killer cells.

Retrovirology 2018 10 6;15(1):68. Epub 2018 Oct 6.

Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Traditionally, NK cells belong to the innate immune system and eliminate virus-infected cells through their germline-encoded receptors. However, NK cells were recently reported to possess memory-like functions that were predominantly provided by hepatic NK cells. Memory properties were mainly documented in contact hypersensitivity models or during cytomegalovirus infections. Read More

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October 2018
1 Read

RNA-induced epigenetic silencing inhibits HIV-1 reactivation from latency.

Retrovirology 2018 10 4;15(1):67. Epub 2018 Oct 4.

Department of Immunovirology and Pathogenesis, Level 5, Wallace Wurth Building, The Kirby Institute for Infection and Immunity, UNSW Sydney, Kensington, Sydney, NSW, 2052, Australia.

Background: Current antiretroviral therapy is effective in controlling HIV-1 infection. However, cessation of therapy is associated with rapid return of viremia from the viral reservoir. Eradicating the HIV-1 reservoir has proven difficult with the limited success of latency reactivation strategies and reflects the complexity of HIV-1 latency. Read More

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October 2018
3 Reads

Adeno-associated virus gene delivery of broadly neutralizing antibodies as prevention and therapy against HIV-1.

Retrovirology 2018 10 1;15(1):66. Epub 2018 Oct 1.

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.

Vectored gene delivery of HIV-1 broadly neutralizing antibodies (bNAbs) using recombinant adeno-associated virus (rAAV) is a promising alternative to conventional vaccines for preventing new HIV-1 infections and for therapeutically suppressing established HIV-1 infections. Passive infusion of single bNAbs has already shown promise in initial clinical trials to temporarily decrease HIV-1 load in viremic patients, and to delay viral rebound from latent reservoirs in suppressed patients during analytical treatment interruptions of antiretroviral therapy. Long-term, continuous, systemic expression of such bNAbs could be achieved with a single injection of rAAV encoding antibody genes into muscle tissue, which would bypass the challenges of eliciting such bNAbs through traditional vaccination in naïve patients, and of life-long repeated passive transfers of such biologics for therapy. Read More

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October 2018
2 Reads

Cellular RelB interacts with the transactivator Tat and enhance HIV-1 expression.

Retrovirology 2018 09 21;15(1):65. Epub 2018 Sep 21.

Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.

Background: Human immunodeficiency virus type 1 (HIV-1) Tat protein plays an essential role in HIV-1 gene transcription. Tat transactivates HIV-1 long terminal repeat (LTR)-directed gene expression through direct interactions with the transactivation-responsive region (TAR) element and other cis elements in the LTR. The TAR-independent Tat-mediated LTR transactivation is modulated by several host factors, but the mechanism is not fully understood. Read More

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September 2018
7 Reads

Potent suppression of HIV-1 cell attachment by Kudzu root extract.

Retrovirology 2018 09 20;15(1):64. Epub 2018 Sep 20.

Department of Immunology and Microbiology, The Scripps Research Institute, 130 Scripps Way, 3C1, Jupiter, FL, 33458, USA.

There is a constant need to improve antiretrovirals against HIV since therapy is limited by cost, side effects and the emergence of drug resistance. Kudzu is a climbing vine from which the root extract (Pueraria lobata), rich in isoflavones and saponins, has long been used in traditional Chinese medicine for a variety of purposes, from weight loss to alcoholism prevention. Here we show that Kudzu root extract significantly inhibits HIV-1 entry into cell lines, primary human CD4T lymphocytes and macrophages, without cell-associated toxicity. Read More

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September 2018
7 Reads

Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing antibodies.

Retrovirology 2018 09 12;15(1):63. Epub 2018 Sep 12.

Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.

An effective HIV-1 vaccine probably will need to be able to induce broadly neutralizing HIV-1 antibodies (bNAbs) in order to be efficacious. The many bNAbs that have been isolated from HIV-1 infected patients illustrate that the human immune system is able to elicit this type of antibodies. The elucidation of the structure of the HIV-1 envelope glycoprotein (Env) trimer has further fueled the search for Env immunogens that induce bNAbs, but while native Env trimer mimetics are often capable of inducing strain-specific neutralizing antibodies (NAbs) against the parental virus, they have not yet induced potent bNAb responses. Read More

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September 2018
1 Read

Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control.

Retrovirology 2018 09 10;15(1):62. Epub 2018 Sep 10.

Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz -FIOCRUZ, Av. Brasil 4365, Rio de Janeiro, RJ, 21045-900, Brazil.

Background: Despite the low level of viral replication in HIV controllers (HICs), studies have reported viral mutations related to escape from cytotoxic T-lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important for understanding viremia control. To analyze the HIV-1 mutational profile and dynamics of CTL-escape mutants in HICs, we selected 11 long-term non-progressor individuals and divided them into the following groups: (1) viremic controllers (VCs; n = 5) and (2) elite controllers (ECs; n = 6). Read More

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September 2018
2 Reads

Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers.

Retrovirology 2018 09 5;15(1):61. Epub 2018 Sep 5.

Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Broadly neutralizing antibodies (bNAbs), able to prevent viral entry by diverse global viruses, are a major focus of HIV vaccine design, with data from animal studies confirming their ability to prevent HIV infection. However, traditional vaccine approaches have failed to elicit these types of antibodies. During chronic HIV infection, a subset of individuals develops bNAbs, some of which are extremely broad and potent. Read More

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September 2018

Engineering multi-specific antibodies against HIV-1.

Retrovirology 2018 08 29;15(1):60. Epub 2018 Aug 29.

Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY, 10016, USA.

As increasing numbers of broadly neutralizing monoclonal antibodies (mAbs) against HIV-1 enter clinical trials, it is becoming evident that combinations of mAbs are necessary to block infection by the diverse array of globally circulating HIV-1 strains and to limit the emergence of resistant viruses. Multi-specific antibodies, in which two or more HIV-1 entry-targeting moieties are engineered into a single molecule, have expanded rapidly in recent years and offer an attractive solution that can improve neutralization breadth and erect a higher barrier against viral resistance. In some unique cases, multi-specific HIV-1 antibodies have demonstrated vastly improved antiviral potency due to increased avidity or enhanced spatiotemporal functional activity. Read More

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August 2018
2 Reads

Nomenclature for endogenous retrovirus (ERV) loci.

Retrovirology 2018 08 28;15(1):59. Epub 2018 Aug 28.

Biology Department, Boston College, Chestnut Hill, Massachusetts, 02467, USA.

Retroviral integration into germline DNA can result in the formation of a vertically inherited proviral sequence called an endogenous retrovirus (ERV). Over the course of their evolution, vertebrate genomes have accumulated many thousands of ERV loci. These sequences provide useful retrospective information about ancient retroviruses, and have also played an important role in shaping the evolution of vertebrate genomes. Read More

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August 2018
34 Reads

Importance of Fc-mediated functions of anti-HIV-1 broadly neutralizing antibodies.

Retrovirology 2018 08 22;15(1):58. Epub 2018 Aug 22.

Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia.

Anti-HIV-1 broadly neutralizing antibodies (BnAbs) exhibit an impressive capacity to protect against chimeric SIV-HIV (SHIV) challenges in macaques and potently reduce viremia in both SHIV-infected macaques and HIV-1-infected humans. There is a body of evidence suggesting Fc-mediated functions of anti-HIV-1 binding antibodies are important in protecting from infection and controlling viremia. The degree to which the efficacy of BnAbs is assisted by Fc-mediated functions is of great interest. Read More

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August 2018
5 Reads

Promoter expression of HERV-K (HML-2) provirus-derived sequences is related to LTR sequence variation and polymorphic transcription factor binding sites.

Retrovirology 2018 08 20;15(1):57. Epub 2018 Aug 20.

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.

Background: Increased transcription of the human endogenous retrovirus group HERV-K (HML-2) is often seen during disease. Although the mechanism of its tissue-specific activation is unclear, research shows that LTR CpG hypomethylation alone is not sufficient to induce its promoter activity and that the transcriptional milieu of a malignant cell contributes, at least partly, to differential HML-2 expression.

Results: We analyzed the relationship between LTR sequence variation and promoter expression patterns in human breast cancer cell lines, finding them to be positively correlated. Read More

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Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir.

Retrovirology 2018 08 17;15(1):56. Epub 2018 Aug 17.

McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.

Background: Integrase strand transfer inhibitors (INSTIs) are recommended for first-line HIV therapy based on their relatively high genetic barrier to resistance. Although raltegravir (RAL) and elvitegravir (EVG) resistance profiles are well-characterized, resistance patterns for dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB) remain largely unknown. Here, in vitro drug selections compared the development of resistance to DTG, BIC, CAB, EVG and RAL using clinical isolates from treatment-naïve primary HIV infection (PHI) cohort participants (n = 12), and pNL4. Read More

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The role of follicular helper CD4 T cells in the development of HIV-1 specific broadly neutralizing antibody responses.

Retrovirology 2018 08 6;15(1):54. Epub 2018 Aug 6.

Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, USA.

The induction of HIV-1-specific antibodies that can neutralize a broad number of isolates is a major goal of HIV-1 vaccination strategies. However, to date no candidate HIV-1 vaccine has successfully elicited broadly neutralizing antibodies of sufficient quality and breadth for protection. In this review, we focus on the role of follicular helper CD4 T-cells (Tfh) in the development of such cross-reactive protective antibodies. Read More

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Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design.

Retrovirology 2018 07 28;15(1):53. Epub 2018 Jul 28.

Department of Immunology, Duke University, DUMC 3010, Durham, NC, 27710, USA.

A central puzzle in HIV-1 research is the inability of vaccination or even infection to reliably elicit humoral responses against broadly neutralizing epitopes in the HIV-1 envelope protein. In infected individuals, broadly neutralizing antibodies (bNAbs) do arise in a substantial minority, but only after 2 or more years of chronic infection. All known bNAbs possess at least one of three traits: a high frequency of somatic hypermutation, a long third complementarity determining region in the antibody heavy chain (HCDR3), or significant poly- or autoreactivity. Read More

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HIV-1 cell-to-cell transmission and broadly neutralizing antibodies.

Retrovirology 2018 07 28;15(1):51. Epub 2018 Jul 28.

Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France.

HIV-1 spreads through contacts between infected and target cells. Polarized viral budding at the contact site forms the virological synapse. Additional cellular processes, such as nanotubes, filopodia, virus accumulation in endocytic or phagocytic compartments promote efficient viral propagation. Read More

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July 2018
12 Reads

Broadly neutralizing antibodies: What is needed to move from a rare event in HIV-1 infection to vaccine efficacy?

Retrovirology 2018 07 28;15(1):52. Epub 2018 Jul 28.

Institute of Medical Virology, University of Zurich, Zurich, Switzerland.

The elicitation of broadly neutralizing antibodies (bnAbs) is considered crucial for an effective, preventive HIV-1 vaccine. Led by the discovery of a new generation of potent bnAbs, the field has significantly advanced over the past decade. There is a wealth of knowledge about the development of bnAbs in natural infection, their specificity, potency, breadth and function. Read More

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Cell surface ectodomain integrity of a subset of functional HIV-1 envelopes is dependent on a conserved hydrophilic domain containing region in their C-terminal tail.

Retrovirology 2018 07 20;15(1):50. Epub 2018 Jul 20.

THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, P.O. Box # 04, Faridabad, Haryana, 1221001, India.

Background: HIV-1 Env gp160 is cleaved to form gp120 and gp41 and the functional HIV-1 Env is a trimer of non-covalently associated heterodimeric subunits, gp120 and gp41. The cleaved, native, trimeric form of Envs expose only broadly neutralizing antibody (bNAb) epitopes while occluding epitopes targeted by non-neutralizing antibodies (non-NAbs). We and others have previously observed that efficient cleavage of Envs into their constituent subunits co-relates with specific binding to bNAbs and poor binding to non-neutralizing antibodies (non-NAbs). Read More

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July 2018
1 Read
4.180 Impact Factor

Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity.

Retrovirology 2018 07 16;15(1):49. Epub 2018 Jul 16.

Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, China.

Background: Semen is a critical vector for human immunodeficiency virus (HIV) sexual transmission and harbors seminal amyloid fibrils that can markedly enhance HIV infection. Semen-derived enhancer of viral infection (SEVI) is one of the best-characterized seminal amyloid fibrils. Due to their highly cationic properties, SEVI fibrils can capture HIV virions, increase viral attachment to target cells, and augment viral fusion. Read More

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July 2018
2 Reads

The invariant arginine within the chromatin-binding motif regulates both nucleolar localization and chromatin binding of Foamy virus Gag.

Retrovirology 2018 07 11;15(1):48. Epub 2018 Jul 11.

CNRS UMR7212, Hôpital St Louis, Inserm U944, Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Background: Nuclear localization of Gag is a property shared by many retroviruses and retrotransposons. The importance of this stage for retroviral replication is still unknown, but studies on the Rous Sarcoma virus indicate that Gag might select the viral RNA genome for packaging in the nucleus. In the case of Foamy viruses, genome encapsidation is mediated by Gag C-terminal domain (CTD), which harbors three clusters of glycine and arginine residues named GR boxes (GRI-III). Read More

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July 2018
5 Reads

Quantitation of the latent HIV-1 reservoir from the sequence diversity in viral outgrowth assays.

Retrovirology 2018 07 5;15(1):47. Epub 2018 Jul 5.

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, MD, USA.

Background: The ability of HIV-1 to integrate into the genomes of quiescent host immune cells, establishing a long-lived latent viral reservoir (LVR), is the primary obstacle to curing these infections. Quantitative viral outgrowth assays (QVOAs) are the gold standard for estimating the size of the replication-competent HIV-1 LVR, measured by the number of infectious units per million (IUPM) cells. QVOAs are time-consuming because they rely on culturing replicate wells to amplify the production of virus antigen or nucleic acid to reproducibly detectable levels. Read More

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July 2018
9 Reads

Global phosphoproteomics of CCR5-tropic HIV-1 signaling reveals reprogramming of cellular protein production pathways and identifies p70-S6K1 and MK2 as HIV-responsive kinases required for optimal infection of CD4+ T cells.

Retrovirology 2018 07 3;15(1):44. Epub 2018 Jul 3.

Department of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.

Background: Viral reprogramming of host cells enhances replication and is initiated by viral interaction with the cell surface. Upon human immunodeficiency virus (HIV) binding to CD4+ T cells, a signal transduction cascade is initiated that reorganizes the actin cytoskeleton, activates transcription factors, and alters mRNA splicing pathways.

Methods: We used a quantitative mass spectrometry-based phosphoproteomic approach to investigate signal transduction cascades initiated by CCR5-tropic HIV, which accounts for virtually all transmitted viruses and the vast majority of viruses worldwide. Read More

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July 2018
19 Reads

CD8 T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication.

Retrovirology 2018 07 3;15(1):46. Epub 2018 Jul 3.

Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.

Background: Development of AIDS vaccines for effective prevention of circulating HIV-1 is required, but no trial has demonstrated definitive effects on the prevention. Several recent T-cell vaccine trials showed no protection against HIV-1 acquisition although the vaccines induced HIV-1-specific T-cell responses, suggesting that the vaccine-induced T cells have insufficient capacities to suppress HIV-1 replication and/or cross-recognize circulating HIV-1. Therefore, it is necessary to develop T-cell vaccines that elicit T cells recognizing shared protective epitopes with strong ability to suppress HIV-1. Read More

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July 2018
15 Reads

Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs.

Retrovirology 2018 07 3;15(1):45. Epub 2018 Jul 3.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, China.

Background: Co-infection with avian leukosis virus subgroup J and reticuloendotheliosis virus induces synergistic pathogenic effects and increases mortality. However, the role of exosomal miRNAs in the molecular mechanism of the synergistic infection of the two viruses remains unknown.

Results: In this study, exosomal RNAs from CEF cells infected with ALV-J, REV or both at the optimal synergistic infection time were analysed by Illumina RNA deep sequencing. Read More

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July 2018
2 Reads

The KT Jeang Retrovirology prize 2018: Eric Freed.

Authors:

Retrovirology 2018 Jul 2;15(1):43. Epub 2018 Jul 2.

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July 2018
9 Reads

The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level.

Retrovirology 2018 06 28;15(1):42. Epub 2018 Jun 28.

HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.

Background: The ability of human immunodeficiency virus type 1 (HIV-1) to form a stable viral reservoir is the major obstacle to an HIV-1 cure and post-transcriptional events contribute to the maintenance of viral latency. RNA surveillance proteins such as UPF1, UPF2 and SMG6 affect RNA stability and metabolism. In our previous work, we demonstrated that UPF1 stabilises HIV-1 genomic RNA (vRNA) and enhances its translatability in the cytoplasm. Read More

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Super-resolution fluorescence microscopy studies of human immunodeficiency virus.

Retrovirology 2018 06 8;15(1):41. Epub 2018 Jun 8.

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.

Super-resolution fluorescence microscopy combines the ability to observe biological processes beyond the diffraction limit of conventional light microscopy with all advantages of the fluorescence readout such as labelling specificity and non-invasive live-cell imaging. Due to their subdiffraction size (< 200 nm) viruses are ideal candidates for super-resolution microscopy studies, and Human Immunodeficiency Virus type 1 (HIV-1) is to date the most studied virus by this technique. This review outlines principles of different super-resolution techniques as well as their advantages and disadvantages for virological studies, especially in the context of live-cell imaging applications. Read More

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June 2018
7 Reads

Obituary: Remembering Professor David Cooper.

Retrovirology 2018 May 24;15(1):40. Epub 2018 May 24.

The Kirby Institute, UNSW Australia, Sydney, NSW, 2052, Australia.

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May 2018
1 Read

HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription.

Retrovirology 2018 05 23;15(1):39. Epub 2018 May 23.

Center for Sickle Cell Disease, Howard University, 1840 7th Street, N.W. HURB1, Suite 202, Washington, DC, 20001, USA.

Background: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functionality.

Results: Mass spectrometry analysis showed primarily Tat Ser-16 phosphorylation in cultured cells. Read More

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May 2018
6 Reads

Efficacies of Cabotegravir and Bictegravir against drug-resistant HIV-1 integrase mutants.

Retrovirology 2018 05 16;15(1):37. Epub 2018 May 16.

HIV Dynamics and Replication Program, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD, USA.

Background: Integrase strand transfer inhibitors (INSTIs) are the class of antiretroviral (ARV) drugs most recently approved by the FDA for the treatment of HIV-1 infections. INSTIs block the strand transfer reaction catalyzed by HIV-1 integrase (IN) and have been shown to potently inhibit infection by wild-type HIV-1. Of the three current FDA-approved INSTIs, Dolutegravir (DTG), has been the most effective, in part because treatment does not readily select for resistant mutants. Read More

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Replacement of feline foamy virus bet by feline immunodeficiency virus vif yields replicative virus with novel vaccine candidate potential.

Retrovirology 2018 05 16;15(1):38. Epub 2018 May 16.

Department of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center, (Deutsches Krebsforschungszentrum Heidelberg, DKFZ), Im Neuenheimer Feld 242, 69120, Heidelberg, Germany.

Background: Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events. Read More

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May 2018
3 Reads

HIV latency reversing agents act through Tat post translational modifications.

Retrovirology 2018 05 11;15(1):36. Epub 2018 May 11.

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.

Background: Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV replication from latently infected cells. A limited number of studies have demonstrated additive effects of LRAs with the viral protein Tat in initiating transcription, but less is known about how LRAs interact with Tat, particularly through basic residues that may be post-translationally modified to alter the behaviour of Tat for processive transcription and co-transcriptional RNA processing.

Results: Here we show that various lysine and arginine mutations reduce the capacity of Tat to induce both transcription and mRNA splicing. Read More

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May 2018
2 Reads

CLIP-related methodologies and their application to retrovirology.

Retrovirology 2018 05 2;15(1):35. Epub 2018 May 2.

Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.

Virtually every step of HIV-1 replication and numerous cellular antiviral defense mechanisms are regulated by the binding of a viral or cellular RNA-binding protein (RBP) to distinct sequence or structural elements on HIV-1 RNAs. Until recently, these protein-RNA interactions were studied largely by in vitro binding assays complemented with genetics approaches. However, these methods are highly limited in the identification of the relevant targets of RBPs in physiologically relevant settings. Read More

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May 2018
1 Read

Reconstruction of a replication-competent ancestral murine endogenous retrovirus-L.

Retrovirology 2018 05 2;15(1):34. Epub 2018 May 2.

Laboratory of Retrovirology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.

Background: About 10% of the mouse genome is composed of endogenous retroviruses (ERVs) that represent a molecular fossil record of past retroviral infections. One such retrovirus, murine ERV-L (MuERV-L) is an env-deficient ERV that has undergone episodic proliferation, with the most recent amplification occurring ~ 2 million years ago. MuERV-L related sequences have been co-opted by mice for antiretroviral defense, and possibly as promoters for some genes that regulate totipotency in early mouse embryos. Read More

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May 2018
1 Read

The HTLV-1 oncoprotein Tax is modified by the ubiquitin related modifier 1 (Urm1).

Retrovirology 2018 04 17;15(1):33. Epub 2018 Apr 17.

Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

Background: Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy secondary to chronic human T-cell lymphotropic virus 1 infection, triggered by the virally encoded oncoprotein Tax. The transforming activity and subcellular localization of Tax is strongly influenced by posttranslational modifications, among which ubiquitylation and SUMOylation have been identified as key regulators of the nuclear/cytoplasmic shuttling of Tax, as well as its ability to activate NF-κB signaling.

Results: Adding to the complex posttranslational modification landscape of Tax, we here demonstrate that Tax also interacts with the ubiquitin-related modifier 1 (Urm1). Read More

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April 2018
3 Reads

HIV-1 protease with leucine zipper fused at N-terminus exhibits enhanced linker amino acid-dependent activity.

Retrovirology 2018 04 14;15(1):32. Epub 2018 Apr 14.

Department of Medical Research, Taipei Veterans General Hospital and Institute of Clinical Medicine, National Yang-Ming University School of Medicine, 201, Sec. 2, Shih-Pai Road, Taipei, 11217, Taiwan.

Background: HIV-1 protease (PR) activation is triggered by Gag-Pol dimerization. Premature PR activation results in reduced virion yields due to enhanced Gag cleavage. A p6* transframe peptide located directly upstream of protease is believed to play a modulating role in PR activation. Read More

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New World feline APOBEC3 potently controls inter-genus lentiviral transmission.

Retrovirology 2018 04 10;15(1):31. Epub 2018 Apr 10.

Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.

Background: The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentiviral replication. In turn, the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated antiviral effect by degrading A3 proteins. Read More

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April 2018
2 Reads

Total HIV DNA: a global marker of HIV persistence.

Retrovirology 2018 04 3;15(1):30. Epub 2018 Apr 3.

Laboratoire de Virologie, APHP Hôpital Necker Enfants Malades, Paris, France.

Among the different markers of HIV persistence in infected cells, total HIV DNA is to date the most widely used. It allows an overall quantification of all viral forms of HIV DNA in infected cells, each playing a different role in HIV replication and pathophysiology. The real-time PCR technology is to date, a precise, sensitive and reproducible technology that allows the description of the distribution of HIV infected cells in blood and tissues. Read More

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April 2018
1 Read

Six-helix bundle completion in the distal C-terminal heptad repeat region of gp41 is required for efficient human immunodeficiency virus type 1 infection.

Retrovirology 2018 04 2;15(1):27. Epub 2018 Apr 2.

Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Background: The native pre-fusion structure of gp120/gp41 complex of human immunodeficiency virus type 1 was recently revealed. In the model, the helices of gp41 (α6, α7, α8, and α9) form a four-helix collar underneath trimeric gp120. Gp41 is a class I fusion protein and mediates membrane fusion by forming a post-fusion structure called the six-helix bundle (6HB). Read More

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April 2018
4 Reads

Why was PERV not transmitted during preclinical and clinical xenotransplantation trials and after inoculation of animals?

Authors:
Joachim Denner

Retrovirology 2018 04 2;15(1):28. Epub 2018 Apr 2.

Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany.

Porcine endogenous retroviruses (PERVs) are present in the genome of all pigs, they infect certain human cells and therefore pose a special risk for xenotransplantation using pig cells, tissues and organs. Xenotransplantation is being developed in order to alleviate the reduced availability of human organs. Despite the fact that PERVs are able to infect certain human cells and cells from other species, transmission of PERVs has not been observed when animals (including non-human primates) were inoculated with PERV preparations or during preclinical xenotransplantations. Read More

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April 2018
1 Read

Pre-exposure prophylaxis (PrEP) in an era of stalled HIV prevention: Can it change the game?

Retrovirology 2018 Apr 2;15(1):29. Epub 2018 Apr 2.

Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Hillbrow Health Precinct, 22 Esselen Street, Hillbrow, Johannesburg, 2001, South Africa.

Pre-exposure prophylaxis (PrEP) for HIV prevention has evolved significantly over the years where clinical trials have now demonstrated the efficacy of oral PrEP, and the field is scaling-up implementation. The WHO and UNAIDS have made PrEP implementation a priority for populations at highest risk, and several countries have developed guidelines and national plans accordingly, largely based on evidence generated by demonstration projects. PrEP presents the opportunity to change the face of HIV prevention by offering a new option for protection against HIV and disrupting current HIV prevention systems. Read More

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April 2018
3 Reads