Alex J Holloway, Tais B Saito, Kubra F Naqvi, Matthew B Huante, Xiuzhen Fan, Joshua G Lisinicchia, Benjamin B Gelman, Janice J Endsley, Mark A Endsley
The study of HIV infection and pathogenicity in physical reservoirs requires a biologically relevant model. The human immune system (HIS) mouse is an established model of HIV infection, but defects in immune tissue reconstitution remain a challenge for examining pathology in tissues. We utilized exogenous injection of the human recombinant FMS-like tyrosine kinase 3 ligand (rFLT-3 L) into the hematopoietic stem cell (HSC) cord blood HIS mouse model to significantly expand the total area of lymph node (LN) and the number of circulating human T cells...
May 2, 2024: Retrovirology
Sarah N'Da Konan, Emmanuel Ségéral, Fabienne Bejjani, Maryam Bendoumou, Mélissa Ait Said, Sarah Gallois-Montbrun, Stéphane Emiliani
No abstract text is available yet for this article.
April 30, 2024: Retrovirology
Sara Coelho Rangel, Michelly Damasceno da Silva, Décio Gilberto Natrielli Filho, Samuel Nascimento Santos, Jonatas Bussador do Amaral, Jefferson Russo Victor, Kevin Cezar Nascimento Silva, Izabela Dorota Tuleta, Carolina Nunes França, Marina Tiemi Shio, Lucas Melo Neves, André Luis Lacerda Bachi, Luiz Henrique da Silva Nali
BACKGROUND: Bipolar disorder (BD) and schizophrenia (SZ) are the two main mental disorders with unknown etiology that significantly impact individuals' quality of life. The potential pro-inflammatory role in their pathogenesis is postulated and Human Endogenous Retrovirus W (HERV-W) is an emerging candidate to modulate this pathogenic finding. HERVs, ancient retroviruses in the human genome, may play roles in inflammation and disease pathogenesis. Despite HERVs' involvement in autoimmune diseases, their influence on mental disorders remains underexplored...
April 22, 2024: Retrovirology
Uri Mbonye, Jonathan Karn
Transcriptionally latent forms of replication-competent proviruses, present primarily in a small subset of memory CD4+ T cells, pose the primary barrier to a cure for HIV-1 infection because they are the source of the viral rebound that almost inevitably follows the interruption of antiretroviral therapy. Over the last 30 years, many of the factors essential for initiating HIV-1 transcription have been identified in studies performed using transformed cell lines, such as the Jurkat T-cell model. However, as highlighted in this review, several poorly understood mechanisms still need to be elucidated, including the molecular basis for promoter-proximal pausing of the transcribing complex and the detailed mechanism of the delivery of P-TEFb from 7SK snRNP...
April 5, 2024: Retrovirology
Sergio P Alpuche-Lazcano, Robert J Scarborough, Anne Gatignol
Human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV) have replicative and latent stages of infection. The status of the viruses is dependent on the cells that harbour them and on different events that change the transcriptional and post-transcriptional events. Non-coding (nc)RNAs are key factors in the regulation of retrovirus replication cycles. Notably, micro (mi)RNAs and long non-coding (lnc)RNAs are important regulators that can induce switches between active transcription-replication and latency of retroviruses and have important impacts on their pathogenesis...
February 29, 2024: Retrovirology
Boying Liang, Tengyue Yan, Huilin Wei, Die Zhang, Lanxiang Li, Zengjing Liu, Wen Li, Yuluan Zhang, Nili Jiang, Qiuxia Meng, Guiyang Jiang, Yanling Hu, Jing Leng
Human endogenous retroviruses (HERVs) are the remnants of ancient retroviral infections integrated into the human genome. Although most HERVs are silenced or rendered inactive by various regulatory mechanisms, they retain the potential to influence the nearby genes. We analyzed the regulatory map of 91 HERV-Ks on neighboring genes in human breast cancer and investigated the impact of HERV-Ks on the tumor microenvironment (TME) and prognosis of breast cancer. Nine RNA-seq datasets were obtained from GEO and NCBI SRA...
February 22, 2024: Retrovirology
Elliott S Chiu, Coby A McDonald, Roderick B Gagne, Henry Dunkleberger, Matthew Moxcey, Sue VandeWoude
Endogenous retroviruses (ERV) are indicators of vertebrate evolutionary history and play important roles as homeostatic regulators. ERV long terminal repeat (LTR) elements may act as cis-activating promoters or trans-activating enhancer elements modifying gene transcription distant from LTR insertion sites. We previously documented that endogenous feline leukemia virus (FeLV)-LTR copy number variation in individual cats tracks inversely with susceptibility to virulent FeLV disease. To evaluate FeLV-LTR insertion characteristics, we assessed enFeLV-LTR integration site diversity in 20 cats from three genetically distinct populations using a baited linker-mediated PCR approach...
February 12, 2024: Retrovirology
Xiaowei Chen, Xiao Wang
The p6 domain of the Gag precursors (Gag p6) in human immunodeficiency virus type 1 (HIV-1) plays multifunctional roles in the viral life cycle. It utilizes the endosomal sorting complex required for transport (ESCRT) system to facilitate viral budding and release from the plasma membrane through the interactions with the ESCRT-I component tumor susceptibility gene 101 (TSG101) and with the ALG-2 interacting protein X (ALIX). Moreover, Gag p6 contributes to viral replication by a range of posttranslational modifications such as SUMOylation, ubiquitination and phosphorylation...
January 23, 2024: Retrovirology
Natacha Faivre, Christel Verollet, Fabrice Dumas
Chemokines are cytokines whose primary role is cellular activation and stimulation of leukocyte migration. They perform their various functions by interacting with G protein-coupled cell surface receptors (GPCRs) and are involved in the regulation of many biological processes such as apoptosis, proliferation, angiogenesis, hematopoiesis or organogenesis. They contribute to the maintenance of the homeostasis of lymphocytes and coordinate the function of the immune system. However, chemokines and their receptors are sometimes hijacked by some pathogens to infect the host organism...
January 23, 2024: Retrovirology
Thumbi Ndung'u
No abstract text is available yet for this article.
October 18, 2023: Retrovirology
Charbel Akkawi, Jerome Feuillard, Felipe Leon Diaz, Khalid Belkhir, Nelly Godefroy, Jean-Marie Peloponese, Marylene Mougel, Sebastien Laine
BACKGROUND: The murine leukemia virus (MLV) has been a powerful model of pathogenesis for the discovery of genes involved in cancer. Its splice donor (SD')-associated retroelement (SDARE) is important for infectivity and tumorigenesis, but the mechanism remains poorly characterized. Here, we show for the first time that P50 protein, which is produced from SDARE, acts as an accessory protein that transregulates transcription and induces cell transformation. RESULTS: By infecting cells with MLV particles containing SDARE transcript alone (lacking genomic RNA), we show that SDARE can spread to neighbouring cells as shown by the presence of P50 in infected cells...
September 12, 2023: Retrovirology
Joy Twentyman, Anthony Khalifeh, Abby L Felton, Michael Emerman, Molly Ohainle
Human immunodeficiency virus (HIV) and other lentiviruses adapt to new hosts by evolving to evade host-specific innate immune proteins that differ in sequence and often viral recognition between host species. Understanding how these host antiviral proteins, called restriction factors, constrain lentivirus replication and transmission is key to understanding the emergence of pandemic viruses like HIV-1. Human TRIM34, a paralogue of the well-characterized lentiviral restriction factor TRIM5α, was previously identified by our lab via CRISPR-Cas9 screening as a restriction factor of certain HIV and SIV capsids...
August 22, 2023: Retrovirology
Merle Flecks, Nicole Fischer, Jacomina Krijnse Locker, Ralf R Tönjes, Antonia W Godehardt
BACKGROUND: Using pigs as organ donors has advanced xenotransplantation to the point that it is almost ready for clinical use. However, there is still a zoonotic risk associated with xenotransplantation, and the potential transmission of porcine endogenous retroviruses needs to be surveyed. Despite significant attempts to eliminate this risk, by the selection of PERV-C free pigs with low expression of PERV-A, -B, and by the genome-wide inactivation of PERV using CRISPR/Cas9, the impact of superinfection resistance (SIR) was not investigated...
August 21, 2023: Retrovirology
Rachel M Podgorski, Jake A Robinson, Mandy D Smith, Suvadip Mallick, Huaqing Zhao, Ronald S Veazey, Dennis L Kolson, Katharine J Bar, Tricia H Burdo
A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV...
August 10, 2023: Retrovirology
María José Lista, AnneCaroline Jousset, Mingpan Cheng, Violaine SaintAndré, Elouan Perrot, Melissa Rodrigues, Carmelo Di Primo, Danielle Gadelle, Elenia Toccafondi, Emmanuel Segeral, Clarisse BerliozTorrent, Stéphane Emiliani, JeanLouis Mergny, Marc Lavigne
No abstract text is available yet for this article.
July 11, 2023: Retrovirology
Estelle Plant, Maxime Bellefroid, Carine Van Lint
Bovine Leukemia Virus (BLV) is the etiological agent of enzootic bovine leukosis, a disease characterized by the neoplastic proliferation of B cells in cattle. While most European countries have introduced efficient eradication programs, BLV is still present worldwide and no treatment is available. A major feature of BLV infection is the viral latency, which enables the escape from the host immune system, the maintenance of a persistent infection and ultimately the tumoral development. BLV latency is a multifactorial phenomenon resulting in the silencing of viral genes due to genetic and epigenetic repressions of the viral promoter located in the 5' Long Terminal Repeat (5'LTR)...
June 2, 2023: Retrovirology
María José Lista, Anne-Caroline Jousset, Mingpan Cheng, Violaine Saint-André, Elouan Perrot, Melissa Rodrigues, Carmelo Di Primo, Danielle Gadelle, Elenia Toccafondi, Emmanuel Segeral, Clarisse Berlioz-Torrent, Stéphane Emiliani, Jean-Louis Mergny, Marc Lavigne
BACKGROUND: Once integrated in the genome of infected cells, HIV-1 provirus is transcribed by the cellular transcription machinery. This process is regulated by both viral and cellular factors, which are necessary for an efficient viral replication as well as for the setting up of viral latency, leading to a repressed transcription of the integrated provirus. RESULTS: In this study, we examined the role of two parameters in HIV-1 LTR promoter activity. We identified DNA topoisomerase1 (TOP1) to be a potent repressor of this promoter and linked this repression to its catalytic domain...
May 30, 2023: Retrovirology
Philippe Colin, Rajesh P Ringe, Anila Yasmeen, Gabriel Ozorowski, Thomas J Ketas, Wen-Hsin Lee, Andrew B Ward, John P Moore, P J Klasse
BACKGROUND: Neutralizing antibodies (NAbs) protect against HIV-1 acquisition in animal models and show promise in treatment of infection. They act by binding to the viral envelope glycoprotein (Env), thereby blocking its receptor interactions and fusogenic function. The potency of neutralization is largely determined by affinity. Less well explained is the persistent fraction, the plateau of remaining infectivity at the highest antibody concentrations. RESULTS: We observed different persistent fractions for neutralization of pseudovirus derived from two Tier-2 isolates of HIV-1, BG505 (Clade A) and B41 (Clade B): it was pronounced for B41 but not BG505 neutralization by NAb PGT151, directed to the interface between the outer and transmembrane subunits of Env, and negligible for either virus by NAb PGT145 to an apical epitope...
May 27, 2023: Retrovirology
Brian Nyiro, Sharon Bright Amanya, Alice Bayiyana, Francis Wasswa, Eva Nabulime, Alex Kayongo, Immaculate Nankya, Gerald Mboowa, David Patrick Kateete, Obondo James Sande
BACKGROUND: Several mechanisms including reduced CCR5 expression, protective HLA, viral restriction factors, broadly neutralizing antibodies, and more efficient T-cell responses, have been reported to account for HIV control among HIV controllers. However, no one mechanism universally accounts for HIV control among all controllers. In this study we determined whether reduced CCR5 expression accounts for HIV control among Ugandan HIV controllers. We determined CCR5 expression among Ugandan HIV controllers compared with treated HIV non-controllers through ex-vivo characterization of CD4 + T cells isolated from archived PBMCs collected from the two distinct groups...
May 25, 2023: Retrovirology
Jessica Eddy, Fisher Pham, Rachel Chee, Esther Park, Nathan Dapprich, Stacy L DeRuiter, Anding Shen
BACKGROUND: With suppressive antiretroviral therapy, HIV infection is well-managed in most patients. However, eradication and cure are still beyond reach due to latent viral reservoirs in CD4 + T cells, particularly in lymphoid tissue environments including the gut associated lymphatic tissues. In HIV patients, there is extensive depletion of T helper cells, particularly T helper 17 cells from the intestinal mucosal area, and the gut is one of the largest viral reservoir sites...
May 18, 2023: Retrovirology
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