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The 7th International Conference on Retroviral Integration

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 2388

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Special Issue Editors

Prof. Dr. Alan N. Engelman

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Guest Editor

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Interests: HIV-1; integrase; integration; capsid; LEDGF/p75; CPSF6; Nup153

Prof. Dr. Mamuka Kvaratskhelia

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Guest Editor

Division of Infectious Diseases, School of Medicine, University of Colorado, Aurora, CO, USA
Interests: HIV integrase; HIV capsid; integrase and capsid host factors; integrase and capsid inhibitors

Prof. Dr. Duane P. Grandgenett

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Guest Editor

Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, Saint Louis, MO, USA
Interests: retrovirus integrases; structural biology; intasomes; assembly mechanisms; concerted integration; HIV-1 strand transfer inhibitors
Special Issues, Collections and Topics in MDPI journals

Dr. Goedele N. Maertens

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Guest Editor

Department of Infectious Disease, Imperial College London, London, UK
Interests: HTLV-1; integrase; integration; intasome assembly; PP2A-B56; integrase inhibitors
Special Issues, Collections and Topics in MDPI journals

Dr. Kristine Yoder

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Guest Editor

Cancer Biology and Genetics, The Ohio State University College of Medicine, Columbus, OH, USA
Interests: HIV; retrovirus; integrase; integration; CRISPR; chromatin
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Integration is the hallmark step of retroviral replication and forms the basis of the latent HIV reservoir that persists in the face of aggressive treatment with antiretroviral inhibitors. HIV cure research accordingly looks to activate latently infected cells for immune clearance or place them in a state of deep sleep to effect a functional cure. This Special Issue will summarize the talks presented at the 7^th International Conference on Retroviral Integration (http://www.retrointegration2023.org/), which will take place in Boulder, Colorado, during the summer of 2023 (July 31 to August 4). In addition to the relationship between sites of integration and HIV latency, the meeting will encompass other subjects topical to integrase and integration research, which include the following:

Structure and function of retroviral intasomes;
Cellular partners of HIV-1 integrase;
Retroviral vectors for human genetic therapy;
Integrase strand transfer inhibitors and drug resistance mechanisms;
Allosteric integrase inhibitors and drug resistance mechanisms;
Preintegration complex structure and function;
Nuclear import of HIV-1 cores/preintegration complexes;
Orthologous systems (retrotransposons; DNA transposons).

Prof. Dr. Alan N. Engelman
Prof. Dr. Mamuka Kvaratskhelia
Prof. Dr. Duane P. Grandgenett
Dr. Goedele N. Maertens
Dr. Kristine Yoder
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

retroviral integration
integrase
latency
HIV cure research
intasomes
gene therapy
integrase strand transfer inhibitors
allosteric integrase inhibitors
preintegration complex
nuclear import
retrotransposition

Published Papers (3 papers)

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Research

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19 pages, 8353 KiB

Open AccessArticle

HIV-1 Capsid Rapidly Induces Long-Lived CPSF6 Puncta in Non-Dividing Cells, but Similar Puncta Already Exist in Uninfected T-Cells

by Anabel Guedán, Megan Burley, Eve R. Caroe and Kate N. Bishop

Viruses 2024, 16(5), 670; https://doi.org/10.3390/v16050670 - 25 Apr 2024

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Abstract

The HIV-1 capsid (CA) protein forms the outer shell of the viral core that is released into the cytoplasm upon infection. CA binds various cellular proteins, including CPSF6, that direct HIV-1 integration into speckle-associated domains in host chromatin. Upon HIV-1 infection, CPSF6 forms puncta in the nucleus. Here, we characterised these CPSF6 puncta further in HeLa cells, T-cells and macrophages and confirmed that integration and reverse transcription are not required for puncta formation. Indeed, we found that puncta formed very rapidly after infection, correlating with the time that CA entered the nucleus. In aphidicolin-treated HeLa cells and macrophages, puncta were detected for the length of the experiment, suggesting that puncta are only lost upon cell division. CA still co-localised with CPSF6 puncta at the latest time points, considerably after the peak of reverse transcription and integration. Intriguingly, the number of puncta induced in macrophages did not correlate with the MOI or the total number of nuclear speckles present in each cell, suggesting that CA/CPSF6 is only directed to a few nuclear speckles. Furthermore, we found that CPSF6 already co-localised with nuclear speckles in uninfected T-cells, suggesting that HIV-1 promotes a natural behaviour of CPSF6. Full article

(This article belongs to the Special Issue The 7th International Conference on Retroviral Integration)

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Review

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37 pages, 1724 KiB

Open AccessReview

Brief Histories of Retroviral Integration Research and Associated International Conferences

by Duane P. Grandgenett and Alan N. Engelman

Viruses 2024, 16(4), 604; https://doi.org/10.3390/v16040604 - 13 Apr 2024

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Abstract

The field of retroviral integration research has a long history that started with the provirus hypothesis and subsequent discoveries of the retroviral reverse transcriptase and integrase enzymes. Because both enzymes are essential for retroviral replication, they became valued targets in the effort to discover effective compounds to inhibit HIV-1 replication. In 2007, the first integrase strand transfer inhibitor was licensed for clinical use, and subsequently approved second-generation integrase inhibitors are now commonly co-formulated with reverse transcriptase inhibitors to treat people living with HIV. International meetings specifically focused on integrase and retroviral integration research first convened in 1995, and this paper is part of the Viruses Special Issue on the 7th International Conference on Retroviral Integration, which was held in Boulder Colorado in the summer of 2023. Herein, we overview key historical developments in the field, especially as they pertain to the development of the strand transfer inhibitor drug class. Starting from the mid-1990s, research advancements are presented through the lens of the international conferences. Our overview highlights the impact that regularly scheduled, subject-specific international meetings can have on community-building and, as a result, on field-specific collaborations and scientific advancements. Full article

(This article belongs to the Special Issue The 7th International Conference on Retroviral Integration)

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14 pages, 11410 KiB

Open AccessReview

Optimizing the Multimerization Properties of Quinoline-Based Allosteric HIV-1 Integrase Inhibitors

by Jian Sun and Jacques J. Kessl

Viruses 2024, 16(2), 200; https://doi.org/10.3390/v16020200 - 28 Jan 2024

Cited by 1 | Viewed by 616

Abstract

Allosteric HIV-1 Integrase (IN) Inhibitors or ALLINIs bind at the dimer interface of the IN, away from the enzymatic catalytic site, and disable viral replication by inducing over-multimerization of IN. Interestingly, these inhibitors are capable of impacting both the early and late stages of viral replication. To better understand the important binding features of multi-substituted quinoline-based ALLINIs, we have surveyed published studies on IN multimerization and antiviral properties of various substituted quinolines at the 4, 6, 7, and 8 positions. Here we show how the efficacy of these inhibitors can be modulated by the nature of the substitutions at those positions. These features not only improve the overall antiviral potencies of these compounds but also significantly shift the selectivity toward the viral maturation stage. Thus, to fully maximize the potency of ALLINIs, the interactions between the inhibitor and multiple IN subunits need to be simultaneously optimized. Full article

(This article belongs to the Special Issue The 7th International Conference on Retroviral Integration)

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