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Pathogens
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Reservoirs of Persistent HIV Infection: Description, Establishment and Maintenance
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Reservoirs of Persistent HIV Infection: Description, Establishment and Maintenance

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Immunological Responses and Immune Defense Mechanisms".

Deadline for manuscript submissions: closed (1 March 2023) | Viewed by 10934

Special Issue Editors

Dr. Natalia Soriano-Sarabia

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Guest Editor
Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20052, USA
Interests: HIV latency; innate immunity; immunotherapy
Dr. Ezequiel Ruiz-Mateos

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Guest Editor
Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, 41004 Sevilla, Spain
Interests: HIV controllers; innate immunity; immunotherapy

Special Issue Information

Dear Colleagues,

The road to developing a complete cure for HIV requires multiple angles of research in order to understand how reservoirs are established and maintained, and how we can target them. Although most studied cell reservoirs are memory CD4 T cells, additional barriers include immune privileged anatomical sites, such as the central nervous system, gastrointestinal tract or lymphoid organs. Important factors that influence the size of the reservoir and potentially our ability to disrupt it include, but are not limited to, the individual characteristics of people living with HIV (PLWH), especially those with extreme phenotypes such as LTNP and elite controllers, access to antiretroviral therapy (ART), and whether therapy is started at the stage of acute or chronic infection.

This Special Issue launched by Pathogens will be devoted to “Cellular reservoirs of persistent HIV infection: beyond CD4 T cells”, and will accept both original research and review articles. This Special Issue will be focus on alternative cellular reservoirs of latent HIV infection, both in peripheral blood and in the tissue in different groups of PLWH. Potential topics include, but are not limited to, the following:

  • HIV persistence in lymphoid tissues;
  • Mechanisms of HIV latency in the gastrointestinal tract;
  • Cellular reservoirs of HIV in elite controllers and long-term non progressors;
  • Targeting the latent HIV reservoir—latency reversing agents and effector cells;
  • The shock and kill strategy in the tissue;
  • Maintenance of latency in macrophages       

This Special Issue will complement the existing literature by adding specific research in the topic.

Dr. Natalia Soriano-Sarabia
Dr. Ezequiel Ruiz-Mateos
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. Pathogens 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 2700 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

  • HIV latency
  • HIV cure
  • elite controllers
  • shock and kill
  • immune response
  • lymph node
  • GALT

Published Papers (4 papers)

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Review

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24 pages, 1220 KiB  
Review
Humanized Mice for Studies of HIV-1 Persistence and Elimination
by Chen Zhang, Lubaba A. Zaman, Larisa Y. Poluektova, Santhi Gorantla, Howard E. Gendelman and Prasanta K. Dash
Pathogens 2023, 12(7), 879; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12070879 - 27 Jun 2023
Cited by 4 | Viewed by 2567
Abstract
A major roadblock to achieving a cure for human immunodeficiency virus type one (HIV-1) is the persistence of latent viral infections in the cells and tissue compartments of an infected human host. Latent HIV-1 proviral DNA persists in resting memory CD4+ T cells [...] Read more.
A major roadblock to achieving a cure for human immunodeficiency virus type one (HIV-1) is the persistence of latent viral infections in the cells and tissue compartments of an infected human host. Latent HIV-1 proviral DNA persists in resting memory CD4+ T cells and mononuclear phagocytes (MPs; macrophages, microglia, and dendritic cells). Tissue viral reservoirs of both cell types reside in the gut, lymph nodes, bone marrow, spleen, liver, kidney, skin, adipose tissue, reproductive organs, and brain. However, despite the identification of virus-susceptible cells, several limitations persist in identifying broad latent reservoirs in infected persons. The major limitations include their relatively low abundance, the precise identification of latently infected cells, and the lack of biomarkers for identifying latent cells. While primary MP and CD4+ T cells and transformed cell lines are used to interrogate mechanisms of HIV-1 persistence, they often fail to accurately reflect the host cells and tissue environments that carry latent infections. Given the host specificity of HIV-1, there are few animal models that replicate the natural course of viral infection with any precision. These needs underlie the importance of humanized mouse models as both valuable and cost-effective tools for studying viral latency and subsequently identifying means of eliminating it. In this review, we discuss the advantages and limitations of humanized mice for studies of viral persistence and latency with an eye toward using these models to test antiretroviral and excision therapeutics. The goals of this research are to use the models to address how and under which circumstances HIV-1 latency can be detected and eliminated. Targeting latent reservoirs for an ultimate HIV-1 cure is the task at hand. Full article
(This article belongs to the Special Issue Reservoirs of Persistent HIV Infection: Description, Establishment and Maintenance)
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16 pages, 1389 KiB  
Review
Controversies in the Design of Strategies for the Cure of HIV Infection
by Alejandro de Gea-Grela and Santiago Moreno
Pathogens 2023, 12(2), 322; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12020322 - 15 Feb 2023
Cited by 1 | Viewed by 1945
Abstract
The cure for chronic human immunodeficiency virus (HIV) infections has been a goal pursued since the antiretroviral therapy that improved the clinical conditions of patients became available. However, the exclusive use of these drugs is not enough to achieve a cure, since the [...] Read more.
The cure for chronic human immunodeficiency virus (HIV) infections has been a goal pursued since the antiretroviral therapy that improved the clinical conditions of patients became available. However, the exclusive use of these drugs is not enough to achieve a cure, since the viral load rebounds when the treatment is discontinued, leading to disease progression. There are several theories and hypotheses about the biological foundations that prevent a cure. The main obstacle appears to be the existence of a latent viral reservoir that cannot be eliminated pharmacologically. This concept is the basis of the new strategies that seek a cure, known as kick and kill. However, there are other lines of study that recognize mechanisms of persistent viral replication in patients under effective treatment, and that would modify the current lines of research on the cure of HIV. Given the importance of these concepts, in this work, we propose to review the most recent evidence on these hypotheses, covering both the evidence that is positioned in favor and against, trying to expose what are some of the challenges that remain to be resolved in this field of research. Full article
(This article belongs to the Special Issue Reservoirs of Persistent HIV Infection: Description, Establishment and Maintenance)
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21 pages, 835 KiB  
Review
HIV Latency in Myeloid Cells: Challenges for a Cure
by Alisha Chitrakar, Marta Sanz, Sanjay B. Maggirwar and Natalia Soriano-Sarabia
Pathogens 2022, 11(6), 611; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11060611 - 24 May 2022
Cited by 9 | Viewed by 3464
Abstract
The use of antiretroviral therapy (ART) for Human Immunodeficiency Virus (HIV) treatment has been highly successful in controlling plasma viremia to undetectable levels. However, a complete cure for HIV is hindered by the presence of replication-competent HIV, integrated in the host genome, that [...] Read more.
The use of antiretroviral therapy (ART) for Human Immunodeficiency Virus (HIV) treatment has been highly successful in controlling plasma viremia to undetectable levels. However, a complete cure for HIV is hindered by the presence of replication-competent HIV, integrated in the host genome, that can persist long term in a resting state called viral latency. Resting memory CD4+ T cells are considered the biggest reservoir of persistent HIV infection and are often studied exclusively as the main target for an HIV cure. However, other cell types, such as circulating monocytes and tissue-resident macrophages, can harbor integrated, replication-competent HIV. To develop a cure for HIV, focus is needed not only on the T cell compartment, but also on these myeloid reservoirs of persistent HIV infection. In this review, we summarize their importance when designing HIV cure strategies and challenges associated to their identification and specific targeting by the “shock and kill” approach. Full article
(This article belongs to the Special Issue Reservoirs of Persistent HIV Infection: Description, Establishment and Maintenance)
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Other

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11 pages, 1197 KiB  
Brief Report
CXCR3 Expression Pattern on CD4+ T Cells and IP-10 Levels with Regard to the HIV-1 Reservoir in the Gut-Associated Lymphatic Tissue
by Max Augustin, Carola Horn, Meryem Seda Ercanoglu, Ute Sandaradura de Silva, Vincent Bondet, Isabelle Suarez, Seung-Hun Chon, Dirk Nierhoff, Elena Knops, Eva Heger, Carlo Vivaldi, Hartmut Schäfer, Mark Oette, Gerd Fätkenheuer, Florian Klein, Darragh Duffy, Michaela Müller-Trutwin and Clara Lehmann
Pathogens 2022, 11(4), 483; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11040483 - 18 Apr 2022
Cited by 3 | Viewed by 2192
Abstract
(1) Background: The gut-associated lymphatic tissue (GALT) represents the largest lymphoid organ, and is considered to be the largest HIV reservoir. The exact size of the GALT reservoir remains unclear. Several markers, such as the chemokine receptor CXCR3 and its pro-inflammatory ligand IP-10, [...] Read more.
(1) Background: The gut-associated lymphatic tissue (GALT) represents the largest lymphoid organ, and is considered to be the largest HIV reservoir. The exact size of the GALT reservoir remains unclear. Several markers, such as the chemokine receptor CXCR3 and its pro-inflammatory ligand IP-10, have been proposed to define the size of HIV reservoirs in the peripheral blood (PB). However, little is known about the role of CXCR3 and IP-10 within the GALT. (2) Methods: We compared the CXCR3 expression, IP-10 levels, and cell-associated HIV DNA of distinct memory CD4+ T cell subsets from the terminal ileum (TI), PB and rectum (RE) of 18 HIV+ patients with antiretroviral therapy (ART), 6 HIV+ treatment-naive patients and 16 healthy controls. (3) Results: While the relative distributions of CD4+ T cell subsets were similar in PB, TI and RE, HIV DNA and CXCR3 expression were markedly increased and IP-10 levels were decreased in TI when compared to PB. No significant correlation was found between the CXCR3 expression and memory CD4+ T cell subsets, IP-10 levels and the HIV DNA amounts measured in PB, TI or RE. (4) Conclusions: During a chronic HIV-1 infection, neither CXCR3 nor IP-10 are indicative of the size of the viral reservoir in the GALT (TI and RE). Full article
(This article belongs to the Special Issue Reservoirs of Persistent HIV Infection: Description, Establishment and Maintenance)
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