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Lingling Xu, Xueqing Zhang, Wenzhao Cheng, Yong Wang, Kaining Yi, Zhilong Wang, Yiling Zhang, Linxiang Shao, Tiejun Zhao
BACKGROUND: Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). ATL carries a poor prognosis due to chemotherapy resistance. Thus, it is urgent to develop new treatment strategies. Hypericin (HY) is a new-type of photosensitizer in the context of photodynamic therapy (PDT) due to its excellent photosensitizing properties and anti-tumor activities. RESULTS: In the present study, we investigated the efficacy of hypericin in ATL cells...
February 19, 2019: Retrovirology
Douglas D Richman, Karissa Huang, Steven M Lada, Xiaoying Sun, Sonia Jain, Marta Massanella, Bryson Menke
Latently infected CD4 lymphocytes preclude cure of HIV infection, even with the most effective antiretroviral therapy. The replication competent latent HIV reservoir has been quantified with the terminal dilution quantitative viral outgrowth assay, which induces virus propagation in CD4+ T cell culture supernatants following cellular activation. Efforts to improve the sensitivity of this inefficient assay have introduced more sensitive p24 ELISA and RNA PCR based endpoints, but these more sensitive endpoints have raised the question whether they are measuring induced replication competent or defective virions...
February 15, 2019: Retrovirology
Shringar Rao, Raquel Amorim, Meijuan Niu, Yann Breton, Michel J Tremblay, Andrew J Mouland
BACKGROUND: Mammalian cells harbour RNA quality control and degradative machineries such as nonsense-mediated mRNA decay that target cellular mRNAs for clearance from the cell to avoid aberrant gene expression. The role of the host mRNA decay pathways in macrophages in the context of human immunodeficiency virus type 1 (HIV-1) infection is yet to be elucidated. Macrophages are directly infected by HIV-1, mediate the dissemination of the virus and contribute to the chronic activation of the inflammatory response observed in infected individuals...
February 7, 2019: Retrovirology
Lili Wang, Sudeh Izadmehr, Edwin Kamau, Xiang-Peng Kong, Benjamin K Chen
BACKGROUND: HIV infection is enhanced by cell adhesions that form between infected and uninfected T cells called virological synapses (VS). VS are initiated by an interaction between Env and CD4 on cell surfaces and result in the recruitment of virus assembly to the site of cell-cell contact. However, the recruitment of Env to the VS and its relationship to Gag recruitment is not well defined. RESULTS: To study the trafficking of HIV-1 Env through the VS, we constructed a molecular clone of HIV carrying a green fluorescent protein-Env fusion protein called, HIV Env-isfGFP-∆V1V2...
January 15, 2019: Retrovirology
Shuhai He, Gaoying Zheng, Defang Zhou, Gen Li, Mingjun Zhu, Xusheng Du, Jing Zhou, Ziqiang Cheng
BACKGROUND: The pathogenesis of immunological tolerance caused by avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, is largely unknown. RESULTS: In this study, the development, differentiation, and immunological capability of B cells and their progenitors infected with ALV-J were studied both morphologically and functionally by using a model of ALV-J congenital infection. Compared with posthatch infection, congenital infection of ALV-J resulted in severe immunological tolerance, which was identified as the absence of detectable specific antivirus antibodies...
January 3, 2019: Retrovirology
Nathalie Désiré, Lorenzo Cerutti, Quentin Le Hingrat, Marine Perrier, Stefan Emler, Vincent Calvez, Diane Descamps, Anne-Geneviève Marcelin, Stéphane Hué, Benoit Visseaux
BACKGROUND: The large and constantly evolving HIV-1 pandemic has led to an increasingly complex diversity. Because of some taxonomic difficulties among the most diverse HIV-1 subtypes, and taking advantage of the large amount of sequence data generated in the recent years, we investigated novel lineage patterns among the main HIV-1 subtypes. RESULTS: All HIV full-length genomes available in public databases were analysed (n = 2017). Maximum likelihood phylogenies and pairwise genetic distance were obtained...
December 22, 2018: Retrovirology
Benjamin J Patters, Santosh Kumar
Human immunodeficiency virus (HIV) infection, despite great advances in antiretroviral therapy, remains a lifelong affliction. Though current treatment regimens can effectively suppress viral load to undetectable levels and preserve healthy immune function, they cannot fully alleviate all symptoms caused by the presence of the virus, such as HIV-associated neurocognitive disorders. Exosomes are small vesicles that transport cellular proteins, RNA, and small molecules between cells as a mechanism of intercellular communication...
December 22, 2018: Retrovirology
Brett D Anderson, Terumasa Ikeda, Seyed Arad Moghadasi, Amber St Martin, William L Brown, Reuben S Harris
BACKGROUND: The APOBEC3 (A3) family of DNA cytosine deaminases provides an innate barrier to infection by retroviruses including HIV-1. A total of five enzymes, A3C, A3D, A3F, A3G and A3H, are degraded by the viral accessory protein Vif and expressed at high levels in CD4+ T cells, the primary reservoir for HIV-1 replication in vivo. Apart from A3C, all of these enzymes mediate restriction of Vif-deficient HIV-1. However, a rare variant of human A3C (Ile188) was shown recently to restrict Vif-deficient HIV-1 in a 293T-based single cycle infection system...
December 17, 2018: Retrovirology
Alinda G Vos, Matthew F Chersich, Kerstin Klipstein-Grobusch, Peter Zuithoff, Michelle A Moorhouse, Samanta T Lalla-Edward, Andrew Kambugu, N Kumarasamy, Diederick E Grobbee, Roos E Barth, Willem D Venter
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...
December 14, 2018: Retrovirology
Hury Hellen Souza de Paula, Ana Cristina Garcia Ferreira, Diogo Gama Caetano, Edson Delatorre, Sylvia Lopes Maia Teixeira, Lara Esteves Coelho, Eduarda Grinsztejn João, Michelle Morata de Andrade, Sandra Wagner Cardoso, Beatriz Grinsztejn, Valdilea Gonçalves Veloso, Mariza Gonçalves Morgado, Monick Lindenmeyer Guimarães, Fernanda Heloise Côrtes
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, CD8+ CD38+ HLA-DR+ T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated...
December 12, 2018: Retrovirology
Viviane Martha Santos de Morais, Elker Lene Santos de Lima, Georgea Gertrudes de Oliveira Mendes Cahú, Thaisa Regina Rocha Lopes, Juliana Prado Gonçales, Maria Tereza Cartaxo Muniz, Maria Rosângela Cunha Duarte Coêlho
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...
November 27, 2018: Retrovirology
Jelle van Schooten, Marit J van Gils
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...
November 26, 2018: Retrovirology
Henning Gruell, Florian Klein
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. While emerging antibody-resistant viral variants have indicated limitations of antibody monotherapy, strategies to enhance the efficacy of broadly neutralizing antibodies in humans are under investigation...
November 16, 2018: Retrovirology
Tadasuke Naito, Jun-Ichirou Yasunaga, Yuichi Mitobe, Kazumasa Shirai, Hiroe Sejima, Hiroshi Ushirogawa, Yuetsu Tanaka, Tatsufumi Nakamura, Kousuke Hanada, Masahiro Fujii, Masao Matsuoka, Mineki Saito
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...
November 6, 2018: Retrovirology
Elizabeth M Anderson, Frank Maldarelli
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. The mechanisms of persistence of these chronically infected long-lived cells is uncertain, but recent research has demonstrated that the presence of the HIV provirus has enduring effects on infected cells...
October 23, 2018: Retrovirology
Laura E McCoy
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. They have also clarified the mechanisms of action of bnAbs and provided detailed descriptions of B cell ontogenies from which they arise...
October 16, 2018: Retrovirology
Bijan Mahboubi, Christina Gavegnano, Dong-Hyun Kim, Raymond F Schinazi, Baek Kim
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...
October 13, 2018: Retrovirology
Elisabeth Littwitz-Salomon, Thanh Nguyen, Simone Schimmer, Ulf Dittmer
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. However, the precise role and the physiologic importance of memory-like NK cells during retroviral infections are still under investigation...
October 6, 2018: Retrovirology
Catalina Méndez, Scott Ledger, Kathy Petoumenos, Chantelle Ahlenstiel, Anthony D Kelleher
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. Consequently, there is a growing need for alternate strategies. Here we explore a "block and lock" approach for enforcing latency to render the provirus unable to restart transcription despite exposure to reactivation stimuli...
October 4, 2018: Retrovirology
Allen Lin, Alejandro B Balazs
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...
October 1, 2018: Retrovirology
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