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  • Article
  • Open Access
1,837 Views
15 Pages

Development and Evaluation of a Novel Relatively Low-Cost Method to Derive HIV-1 Integration Sites and Proviral Sequences

  • Samantha R. Hardy,
  • Sheila Styrchak,
  • Tim De Meyer,
  • Laurens Lambrechts and ,
  • Tine Struyve,
  • Basiel Cole,
  • Liesbet Termote,
  • Sherry McLaughlin,
  • James I. Mullins and
  • Lisa M. Frenkel
  • + 6 authors+ 1 author

2 March 2026

In people taking antiretroviral therapy (ART) for HIV infection, the methods to characterize latent and active HIV reservoirs remain costly and labor-intensive. Our objective was to develop a relatively low-cost technique to amplify and sequence the...

(This article belongs to the Section Human Virology and Viral Diseases)
  • Review
  • Open Access
9 Citations
5,121 Views
14 Pages

10 December 2021

Development of potential HIV-1 curative interventions requires accurate characterization of the proviral reservoir, defined as host-integrated viral DNA genomes that drive rebound of viremia upon halting ART (antiretroviral therapy). Evaluation of su...

(This article belongs to the Section Human Virology and Viral Diseases)
  • Article
  • Open Access
13 Citations
4,530 Views
17 Pages

7 May 2022

Bovine leukemia virus (BLV) infects cattle and integrates into host DNA, causing enzootic bovine leukosis (EBL), an aggressive B-cell lymphoma. Here, we developed a novel proviral DNA-capture sequencing (proviral DNA-capture-seq) method investigating...

(This article belongs to the Special Issue Novel Diagnostic Technologies for SARS-CoV-2 and Other Emerging Viruses)
  • Review
  • Open Access
29 Citations
7,438 Views
19 Pages

17 September 2021

More than 50% of the HIV-1 latent reservoir is maintained by clonal expansion. The clonally expanded HIV-1-infected cells can contribute to persistent nonsuppressible low-level viremia and viral rebound. HIV-1 integration site and proviral genome lan...

(This article belongs to the Special Issue HIV Infection and Spread between T Cells)
  • Article
  • Open Access
13 Citations
5,720 Views
13 Pages

Tracking HIV-1-Infected Cell Clones Using Integration Site-Specific qPCR

  • Leah D. Brandt,
  • Shuang Guo,
  • Kevin W. Joseph,
  • Jana L. Jacobs and ,
  • Asma Naqvi,
  • John M. Coffin,
  • Mary F. Kearney,
  • Elias K. Halvas,
  • Xiaolin Wu and
  • John W. Mellors
  • + 6 authors+ 1 author

25 June 2021

Efforts to cure HIV-1 infection require better quantification of the HIV-1 reservoir, particularly the clones of cells harboring replication-competent (intact) proviruses, termed repliclones. The digital droplet PCR assays commonly used to quantify i...

(This article belongs to the Special Issue Mechanisms of Viral Persistence)
  • Article
  • Open Access
3 Citations
1,732 Views
22 Pages

Diversity of Integration Sites of Bovine Leukemia Virus (BLV) and Roles of Genes Related to Development of BLV-Induced Lymphoma in a Large Cohort

  • Ryosuke Matsuura,
  • Meripet Polat Yamanaka,
  • Noriko Fukushi,
  • Susumu Saito and ,
  • Keisuke Fukumoto,
  • Kazuyoshi Hosomichi,
  • Shin-nosuke Takeshima and
  • Yoko Aida
  • + 3 authors+ 0 author

Bovine leukemia virus (BLV) causes enzootic bovine leukosis (EBL), yet its pathogenic mechanisms remain largely unclear. In particular, the role of BLV genomic integration sites (IS(s)) in BLV-induced leukemogenesis has not been fully elucidated. Her...

(This article belongs to the Special Issue The Interaction Between Cell and Virus, 3rd Edition)
  • Article
  • Open Access
24 Citations
4,822 Views
12 Pages

30 October 2019

Based on the up-regulation of the proviral integration site of the Moloney murine leukemia virus (Pim) kinase family (Pim1, 2, and 3) observed in several types of leukemias and lymphomas, the development of pan-Pim inhibitors is an attractive therape...

(This article belongs to the Section Physical Chemistry and Chemical Physics)
  • Review
  • Open Access
17 Citations
6,480 Views
23 Pages

The Impact of Cellular Proliferation on the HIV-1 Reservoir

  • Maria C. Virgilio and
  • Kathleen L. Collins

21 January 2020

Human immunodeficiency virus (HIV) is a chronic infection that destroys the immune system in infected individuals. Although antiretroviral therapy is effective at preventing infection of new cells, it is not curative. The inability to clear infection...

(This article belongs to the Special Issue HIV-1 Latency: Regulation and Reversal)
  • Article
  • Open Access
14 Citations
4,489 Views
17 Pages

Isolation of a Human Betaretrovirus from Patients with Primary Biliary Cholangitis

  • Mariam Goubran,
  • Weiwei Wang,
  • Stanislav Indik,
  • Alexander Faschinger and ,
  • Shawn T. Wasilenko,
  • Jasper Bintner,
  • Eric J. Carpenter,
  • Guangzhi Zhang,
  • Paulo Nuin and
  • Andrew L. Mason
  • + 7 authors+ 2 authors

24 April 2022

A human betaretrovirus (HBRV) has been linked with the autoimmune liver disease, primary biliary cholangitis (PBC), and various cancers, including breast cancer and lymphoma. HBRV is closely related to the mouse mammary tumor virus, and represents th...

(This article belongs to the Special Issue Human Betaretrovirus and Related Diseases)
  • Review
  • Open Access
3 Citations
1,969 Views
47 Pages

The block-and-lock strategy aims to achieve a functional cure for human immunodeficiency virus type 1 (HIV-1) infection by enforcing durable, drug-independent silencing of proviral transcription. Several latency-promoting agents have been described t...

(This article belongs to the Special Issue Advances on Viral Immunology and Pathogenesis of Viral Infections)
  • Article
  • Open Access
2 Citations
2,036 Views
17 Pages

Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting

  • Dalibor Miklík,
  • Martina Slavková,
  • Dana Kučerová,
  • Chahrazed Mekadim and ,
  • Jakub Mrázek and
  • Jiří Hejnar
  • + 1 author+ 0 author

25 September 2024

Retroviruses integrate into the genomes of infected host cells to form proviruses, a genetic platform for stable viral gene expression. Epigenetic silencing can, however, hamper proviral transcriptional activity. As gammaretroviruses (γRVs) pre...

(This article belongs to the Section General Virology)
  • Article
  • Open Access
5 Citations
5,366 Views
11 Pages

10 February 2018

Avian leukosis virus (ALV) is a simple retrovirus that can induce B-cell lymphoma in chicken(s) and other birds by insertional mutagenesis. The promoter region of telomerase reverse transcriptase (TERT) has been identified as an important integration...

(This article belongs to the Special Issue Homage to Jan Svoboda: Recent Advances in Topics Pioneered by his Prague School)
  • Review
  • Open Access
33 Citations
8,807 Views
12 Pages

Insight in HIV Integration Site Selection Provides a Block-and-Lock Strategy for a Functional Cure of HIV Infection

  • Zeger Debyser,
  • Gerlinde Vansant,
  • Anne Bruggemans,
  • Julie Janssens and
  • Frauke Christ

26 December 2018

Despite significant improvements in therapy, the HIV/AIDS pandemic remains an important threat to public health. Current treatments fail to eradicate HIV as proviral DNA persists in long-living cellular reservoirs, leading to viral rebound whenever t...

(This article belongs to the Special Issue Homage to Jan Svoboda: Recent Advances in Topics Pioneered by his Prague School)
  • Article
  • Open Access
10 Citations
9,149 Views
19 Pages

24 November 2015

Transcriptome analysis of polar bear (Ursus maritimus) tissues identified sequences with similarity to Porcine Endogenous Retroviruses (PERV). Based on these sequences, four proviral copies and 15 solo long terminal repeats (LTRs) of a newly describe...

(This article belongs to the Special Issue Next Generation Sequencing: New Developments and Discoveries in Virology)
  • Article
  • Open Access
13 Citations
6,091 Views
17 Pages

8 March 2018

Individual groups of retroviruses and retroviral vectors differ in their integration site preference and interaction with the host genome. Hence, immediately after infection genome-wide distribution of integrated proviruses is non-random. During long...

(This article belongs to the Special Issue Homage to Jan Svoboda: Recent Advances in Topics Pioneered by his Prague School)
  • Review
  • Open Access
21 Citations
4,766 Views
12 Pages

21 November 2022

The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases is a family of serine/threonine kinases that regulates numerous signaling networks that promote cell growth, proliferation, and survival. PIM kinases are commonly upregulat...

(This article belongs to the Special Issue Inhibiting Immune Checkpoint-Expressing Cells for Tumor Therapy)
  • Review
  • Open Access
16 Citations
6,251 Views
26 Pages

Fighting HIV-1 Persistence: At the Crossroads of “Shoc-K and B-Lock”

  • Chiara Acchioni,
  • Enrico Palermo,
  • Silvia Sandini,
  • Marta Acchioni and ,
  • John Hiscott and
  • Marco Sgarbanti
  • + 1 author+ 0 author

20 November 2021

Despite the success of highly active antiretroviral therapy (HAART), integrated HIV-1 proviral DNA cannot be eradicated from an infected individual. HAART is not able to eliminate latently infected cells that remain invisible to the immune system. Vi...

(This article belongs to the Special Issue Pathogenesis, Molecular Epidemiology, and Immune Response to Lentiviral Infections)
  • Article
  • Open Access
26 Citations
6,129 Views
20 Pages

New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation

  • Bruno Oyallon,
  • Marie Brachet-Botineau,
  • Cédric Logé,
  • Thomas Robert and ,
  • Stéphane Bach,
  • Sajida Ibrahim,
  • William Raoul,
  • Cécile Croix,
  • Pascal Berthelot and
  • Caroline Denevault-Sabourin
  • + 9 authors+ 4 authors

6 February 2021

Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playin...

(This article belongs to the Special Issue Kinase Inhibitors 2021)
  • Review
  • Open Access
44 Citations
10,011 Views
41 Pages

HIV-1 Proviral Transcription and Latency in the New Era

  • Ashutosh Shukla,
  • Nora-Guadalupe P. Ramirez and
  • Iván D’Orso

18 May 2020

Three decades of extensive work in the HIV field have revealed key viral and host cell factors controlling proviral transcription. Various models of transcriptional regulation have emerged based on the collective information from in vitro assays and...

(This article belongs to the Special Issue HIV-1 Transcription Regulation)
  • Review
  • Open Access
8 Citations
4,933 Views
17 Pages

Is the Central Nervous System Reservoir a Hurdle for an HIV Cure?

  • Nazanin Mohammadzadeh,
  • Nicolas Chomont,
  • Jerome Estaquier,
  • Eric A. Cohen and
  • Christopher Power

5 December 2023

There is currently no cure for HIV infection although adherence to effective antiretroviral therapy (ART) suppresses replication of the virus in blood, increases CD4+ T-cell counts, reverses immunodeficiency, and increases life expectancy. Despite th...

(This article belongs to the Special Issue Neurotropic Viral Pathogens)
  • Article
  • Open Access
7 Citations
4,780 Views
31 Pages

Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases

  • Viet Hung Dao,
  • Isabelle Ourliac-Garnier,
  • Cédric Logé,
  • Florence O. McCarthy and ,
  • Stéphane Bach,
  • Teresinha Gonçalves da Silva,
  • Caroline Denevault-Sabourin,
  • Jérôme Thiéfaine,
  • Blandine Baratte and
  • Pascal Marchand
  • + 9 authors+ 4 authors

30 October 2021

Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as t...

(This article belongs to the Special Issue Kinase Inhibitors 2021)
  • Article
  • Open Access
26 Citations
5,154 Views
26 Pages

HIV-1 Gag Forms Ribonucleoprotein Complexes with Unspliced Viral RNA at Transcription Sites

  • Kevin M. Tuffy,
  • Rebecca J. Kaddis Maldonado,
  • Jordan Chang,
  • Paul Rosenfeld and ,
  • Alan Cochrane and
  • Leslie J. Parent
  • + 1 author+ 0 author

9 November 2020

The ability of the retroviral Gag protein of Rous sarcoma virus (RSV) to transiently traffic through the nucleus is well-established and has been implicated in genomic RNA (gRNA) packaging Although other retroviral Gag proteins (human immunodeficienc...

(This article belongs to the Special Issue Function and Structure of Viral Ribonucleoproteins Complexes)
  • Review
  • Open Access
40 Citations
8,788 Views
35 Pages

11 May 2020

HIV-1 establishes a life-long infection when proviral DNA integrates into the host genome. The provirus can then either actively transcribe RNA or enter a latent state, without viral production. The switch between these two states is governed in grea...

(This article belongs to the Special Issue HIV-1 Transcription Regulation)
  • Article
  • Open Access
8 Citations
3,518 Views
13 Pages

PIM Kinases as Potential Biomarkers and Therapeutic Targets in Inflammatory Arthritides

  • Elisa Assirelli,
  • Jacopo Ciaffi,
  • Valentina Scorcu,
  • Susanna Naldi and ,
  • Veronica Brusi,
  • Luana Mancarella,
  • Lucia Lisi,
  • Federica Pignatti,
  • Francesco Ursini and
  • Simona Neri
  • + 5 authors+ 0 author

The Proviral Integration site for the Moloney murine leukemia virus (PIM)-1 kinase and its family members (PIM-2 and PIM-3) regulate several cellular functions including survival, proliferation, and apoptosis. Recent studies showed their involvement...

(This article belongs to the Special Issue Molecular and Therapeutic Research in Rheumatoid Arthritis)
  • Communication
  • Open Access
111 Views
14 Pages

Distinct HIV-1 Proviral Integration Region Landscapes Across Acute Naïve, Chronic Naïve, and Successfully Treated Patient Cohorts

  • Giuseppe Sberna,
  • Giulia Berno,
  • Cesare Ernesto Maria Gruber,
  • Gabriella Rozera and ,
  • Elisabetta Lazzari,
  • Lavinia Fabeni,
  • Federica Forbici,
  • Valentina Mazzotta,
  • Roberta Gagliardini and
  • Isabella Abbate
  • + 10 authors+ 5 authors

28 October 2026

HIV-1 proviral integration into the human genome dictates viral and host gene expression, as well as HIV reservoir persistence. This study analyzed insertion site (IS) landscapes in three groups of people with HIV (PWH): acute (AHI) naïve (n = 8...

(This article belongs to the Special Issue HIV Reservoirs, Latency, and the Factors Responsible (2nd Edition))
  • Review
  • Open Access
87 Citations
17,707 Views
14 Pages

PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation of Ovarian Cancer

  • Aziz Ur Rehman Aziz,
  • Sumbal Farid,
  • Kairong Qin,
  • Hanqin Wang and
  • Bo Liu

4 February 2018

Ovarian cancer is a medical term that includes a number of tumors with different molecular biology, phenotypes, tumor progression, etiology, and even different diagnosis. Some specific treatments are required to address this heterogeneity of ovarian...

(This article belongs to the Special Issue TOR Signaling Pathway)
  • Feature Paper
  • Article
  • Open Access
11 Citations
4,401 Views
14 Pages

16 March 2022

Proviral integration sites for Moloney murine leukemia virus (PIM) kinases are upregulated at the protein level in response to hypoxia and have multiple protumorigenic functions, promoting cell growth, survival, and angiogenesis. However, the mechani...

(This article belongs to the Special Issue Hypoxia and Cancer: Mechanisms of Resistance and Metastasis)
  • Article
  • Open Access
7 Citations
3,714 Views
19 Pages

Engineered Fully Human Single-Chain Monoclonal Antibodies to PIM2 Kinase

  • Kanasap Kaewchim,
  • Kittirat Glab-ampai,
  • Kodchakorn Mahasongkram,
  • Monrat Chulanetra and ,
  • Watee Seesuay,
  • Wanpen Chaicumpa and
  • Nitat Sookrung
  • + 2 authors+ 0 author

25 October 2021

Proviral integration site of Moloney virus-2 (PIM2) is overexpressed in multiple human cancer cells and high level is related to poor prognosis; thus, PIM2 kinase is a rational target of anti-cancer therapeutics. Several chemical inhibitors targeting...

(This article belongs to the Special Issue Computational Methods for Drug Discovery and Design II)
  • Review
  • Open Access
146 Citations
17,919 Views
23 Pages

16 June 2016

HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and...

(This article belongs to the Section Animal Viruses)
  • Article
  • Open Access
8 Citations
4,539 Views
25 Pages

HIV-1 Transcription Inhibition Using Small RNA-Binding Molecules

  • Pooja Khatkar,
  • Gifty Mensah,
  • Shangbo Ning,
  • Maria Cowen and ,
  • Yuriy Kim,
  • Anastasia Williams,
  • Fardokht A. Abulwerdi,
  • Yunjie Zhao,
  • Chen Zeng and
  • Fatah Kashanchi
  • + 6 authors+ 1 author

25 December 2023

The HIV-1 transactivator protein Tat interacts with the transactivation response element (TAR) at the three-nucleotide UCU bulge to facilitate the recruitment of transcription elongation factor-b (P-TEFb) and induce the transcription of the integrate...

(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
  • Article
  • Open Access
2 Citations
3,320 Views
13 Pages

4 November 2024

The persistent challenge of idiopathic pulmonary fibrosis (IPF), characterized by disease progression and high mortality, underscores the urgent need for innovative therapeutic strategies. We have developed a novel small molecule—catechin deriv...

(This article belongs to the Special Issue Role of Natural Compounds in Human Health and Disease)
  • Review
  • Open Access
2 Citations
2,771 Views
27 Pages

22 January 2026

HTLV-1 and HIV-1 represent biologically significant, structurally close, and equally problematic yet divergent human retroviruses. Although both infect CD4+ T cells and share similar structural elements, they differ markedly in genomic stability, tra...

(This article belongs to the Special Issue Unraveling the Pathogenesis of Persistent Virus Infection)