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Human Immunodeficiency Virus (HIV)
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Human Immunodeficiency Virus (HIV)

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 16753

Special Issue Editors

Dr. Mª Ángeles Muñoz Fernández

E-Mail Website
Guest Editor
Laboratorio InmunoBiología Molecular del Hospital General Universitario Gregorio Marañón, Spain
Interests: Human Immunodeficiency Virus; herpes virus; immunity; immunopathology; virus-cell interaction; nanotechnology; vaccines
Dr. Ignacio Rodríguez Relaño

E-Mail Website
Guest Editor
Laboratorio InmunoBiología Molecular del Hospital General Universitario Gregorio Marañón, Spain
Interests: Human Immunodeficiency Virus; Human Citomegalovirus; immunity; immunopathology; virus-cell interaction; nanotechnology; viral latency

Special Issue Information

Dear Colleagues,

Human immunodeficiency virus (HIV) remains a major public health concern due to the increasing number of infections (1.7 million new infections in 2019, with 38 million infected globally). HIV’s ability to persist in latent reservoirs is one of the major barriers to its eradication. Thus, we urgently need to develop new strategies to understand the mechanisms underlying the latency of HIV and new compounds to minimize the damage to cells of infected patients. In addition, new vaccine strategies are needed to decrease the global number of infections. Consequently, molecular and clinical research is important to improving our knowledge of viral and cellular factors that impact the pathogenicity and latency of HIV. Moreover, the analysis of interdependent consequences of viral factors and host responses has the potential to reveal important pathways involved in the pathogenicity of HIV. In this Special Issue, we invite contributors to publish their research on HIV’s molecular biology, the molecular basis of HIV’s pathogenicity, latent infection, innate immune evasion strategies, and the development of new vaccines.

Dr. Mª Ángeles Muñoz Fernández
Dr. Ignacio Rodríguez Relaño
Guest Editors

Manuscript Submission Information

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • HIV
  • immunopathology
  • virus–cell interaction
  • viral latency
  • immune signaling pathways
  • vaccines

Published Papers (5 papers)

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Research

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22 pages, 2009 KiB  
Article
Combinations of Histone Deacetylase Inhibitors with Distinct Latency Reversing Agents Variably Affect HIV Reactivation and Susceptibility to NK Cell-Mediated Killing of T Cells That Exit Viral Latency
by Daniela A. Covino, Maria G. Desimio and Margherita Doria
Int. J. Mol. Sci. 2021, 22(13), 6654; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136654 - 22 Jun 2021
Cited by 8 | Viewed by 2398
Abstract
The ‘shock-and-kill’ strategy to purge the latent HIV reservoir relies on latency-reversing agents (LRAs) to reactivate the provirus and subsequent immune-mediated killing of HIV-expressing cells. Yet, clinical trials employing histone deacetylase inhibitors (HDACis; Vorinostat, Romidepsin, Panobinostat) as LRAs failed to reduce the HIV [...] Read more.
The ‘shock-and-kill’ strategy to purge the latent HIV reservoir relies on latency-reversing agents (LRAs) to reactivate the provirus and subsequent immune-mediated killing of HIV-expressing cells. Yet, clinical trials employing histone deacetylase inhibitors (HDACis; Vorinostat, Romidepsin, Panobinostat) as LRAs failed to reduce the HIV reservoir size, stressing the need for more effective latency reversal strategies, such as 2-LRA combinations, and enhancement of the immune responses. Interestingly, several LRAs are employed to treat cancer because they up-modulate ligands for the NKG2D NK-cell activating receptor on tumor cells. Therefore, using in vitro T cell models of HIV latency and NK cells, we investigated the capacity of HDACis, either alone or combined with a distinct LRA, to potentiate the NKG2D/NKG2D ligands axis. While Bortezomib proteasome inhibitor was toxic for both T and NK cells, the GS-9620 TLR-7 agonist antagonized HIV reactivation and NKG2D ligand expression by HDACis. Conversely, co-administration of the Prostratin PKC agonist attenuated HDACi toxicity and, when combined with Romidepsin, stimulated HIV reactivation and further up-modulated NKG2D ligands on HIV+ T cells and NKG2D on NK cells, ultimately boosting NKG2D-mediated viral suppression by NK cells. These findings disclose limitations of LRA candidates and provide evidence that NK cell suppression of reactivated HIV may be modulated by specific 2-LRA combinations. Full article
(This article belongs to the Special Issue Human Immunodeficiency Virus (HIV))
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17 pages, 3814 KiB  
Article
Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
by Darío Manzanares, María Dolores Pérez-Carrión, José Luis Jiménez Blanco, Carmen Ortiz Mellet, José Manuel García Fernández and Valentín Ceña
Int. J. Mol. Sci. 2020, 21(23), 9306; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239306 - 06 Dec 2020
Cited by 10 | Viewed by 3368
Abstract
Small interfering ribonucleic acid (siRNA) has the potential to revolutionize therapeutics since it can knockdown very efficiently the target protein. It is starting to be widely used to interfere with cell infection by HIV. However, naked siRNAs are unable to get into the [...] Read more.
Small interfering ribonucleic acid (siRNA) has the potential to revolutionize therapeutics since it can knockdown very efficiently the target protein. It is starting to be widely used to interfere with cell infection by HIV. However, naked siRNAs are unable to get into the cell, requiring the use of carriers to protect them from degradation and transporting them across the cell membrane. There is no information about which is the most efficient endocytosis route for high siRNA transfection efficiency. One of the most promising carriers to efficiently deliver siRNA are cyclodextrin derivatives. We have used nanocomplexes composed of siRNA and a β-cyclodextrin derivative, AMC6, with a very high transfection efficiency to selectively knockdown clathrin heavy chain, caveolin 1, and p21 Activated Kinase 1 to specifically block clathrin-mediated, caveolin-mediated and macropinocytosis endocytic pathways. The main objective was to identify whether there is a preferential endocytic pathway associated with high siRNA transfection efficiency. We have found that macropinocytosis is the preferential entry pathway for the nanoparticle and its associated siRNA cargo. However, blockade of macropinocytosis does not affect AMC6-mediated transfection efficiency, suggesting that macropinocytosis blockade can be functionally compensated by an increase in clathrin- and caveolin-mediated endocytosis. Full article
(This article belongs to the Special Issue Human Immunodeficiency Virus (HIV))
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15 pages, 3279 KiB  
Article
Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells
by Mohammad Sadraeian, Calise Bahou, Edgar Ferreira da Cruz, Luíz Mário Ramos Janini, Ricardo Sobhie Diaz, Ross W. Boyle, Vijay Chudasama and Francisco Eduardo Gontijo Guimarães
Int. J. Mol. Sci. 2020, 21(23), 9151; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239151 - 01 Dec 2020
Cited by 16 | Viewed by 3133
Abstract
Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to [...] Read more.
Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers (PSs) with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells. Full article
(This article belongs to the Special Issue Human Immunodeficiency Virus (HIV))
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Review

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20 pages, 746 KiB  
Review
Emergence of Nanotechnology to Fight HIV Sexual Transmission: The Trip of G2-S16 Polyanionic Carbosilane Dendrimer to Possible Pre-Clinical Trials
by Ignacio Relaño-Rodríguez and Maria Ángeles Muñoz-Fernández
Int. J. Mol. Sci. 2020, 21(24), 9403; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249403 - 10 Dec 2020
Cited by 11 | Viewed by 2632
Abstract
Development of new, safe, and effective microbicides to prevent human immunodeficiency virus HIV sexual transmission is needed. Unfortunately, most microbicides proved ineffective to prevent the risk of HIV-infection in clinical trials. We are working with G2-S16 polyanionic carbosilane dendrimer (PCD) as a new [...] Read more.
Development of new, safe, and effective microbicides to prevent human immunodeficiency virus HIV sexual transmission is needed. Unfortunately, most microbicides proved ineffective to prevent the risk of HIV-infection in clinical trials. We are working with G2-S16 polyanionic carbosilane dendrimer (PCD) as a new possible vaginal topical microbicide, based on its short reaction times, wide availability, high reproducibility, and quantitative yields of reaction. G2-S16 PCD exerts anti-HIV activity at an early stage of viral replication, by blocking gp120/CD4/CCR5 interaction, and providing a barrier against infection for long periods of time. G2-S16 PCD was stable at different pH values, as well as in the presence of seminal fluids. It maintained the anti-HIV activity against R5/X4 HIV over time, did not generate any type of drug resistance, and retained the anti-HIV effect when exposed to semen-enhanced viral infection. Importantly, G2-S16 PCD did not modify vaginal microbiota neither in vitro or in vivo. Histopathological examination did not show vaginal irritation, inflammation, lesions, or damage in the vaginal mucosa, after administration of G2-S16 PCD at different concentrations and times in female mice and rabbit animal models. Based on these promising data, G2-S16 PCD could become a good, safe, and readily available candidate to use as a topical vaginal microbicide against HIV. Full article
(This article belongs to the Special Issue Human Immunodeficiency Virus (HIV))
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29 pages, 1790 KiB  
Review
Nanosystems Applied to HIV Infection: Prevention and Treatments
by Micaela A. Macchione, Dariana Aristizabal Bedoya, Francisco N. Figueroa, María Ángeles Muñoz-Fernández and Miriam C. Strumia
Int. J. Mol. Sci. 2020, 21(22), 8647; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228647 - 17 Nov 2020
Cited by 9 | Viewed by 4039
Abstract
Sexually-transmitted infections (STIs) are a global health concern worldwide as they cause acute diseases, infertility, and significant mortality. Among the bacterial, viral, and parasitic pathogens that can be sexually transmitted, human immunodeficiency virus (HIV) has caused one of the most important pandemic diseases, [...] Read more.
Sexually-transmitted infections (STIs) are a global health concern worldwide as they cause acute diseases, infertility, and significant mortality. Among the bacterial, viral, and parasitic pathogens that can be sexually transmitted, human immunodeficiency virus (HIV) has caused one of the most important pandemic diseases, which is acquired immune deficiency syndrome (AIDS). 32.7 million people have died from AIDS-related illnesses since the start of the epidemic. Moreover, in 2019, 38 million people were living with HIV worldwide. The need to deal with this viral infection becomes more obvious, because it represents not only a problem for public health, but also a substantial economic problem. In this context, it is necessary to focus efforts on developing methods for prevention, detection and treatment of HIV infections that significantly reduce the number of newly infected people and provide a better quality of life for patients. For several decades, biomedical research has been developed allowing quick solutions through the contribution of effective tools. One of them is the use of polymers as vehicles, drug carrier agents, or as macromolecular prodrugs. Moreover, nanosystems (NSs) play an especially important role in the diagnosis, prevention, and therapy against HIV infection. The purpose of this work is to review recent research into diverse NSs as potential candidates for prevention and treatment of HIV infection. Firstly, this review highlights the advantages of using nanosized structures for these medical applications. Furthermore, we provide an overview of different types of NSs used for preventing or combating HIV infection. Then, we briefly evaluate the most recent developments associated with prevention and treatment alternatives. Additionally, the implications of using different NSs are also addressed. Full article
(This article belongs to the Special Issue Human Immunodeficiency Virus (HIV))
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