Review
Virology
Katherine M. Bricker, Ann Chahroudi, Maud Mavigner
Summary: The "shock and kill" strategy for treating HIV-1 involves reactivating latent infected cells with LRAs, exposing them to immune system killing. Progress has been made in this area through the NHP model, which has both advantages and limitations for evaluating treatment efficacy.
Review
Immunology
Anna Kula-Pacurar, Anthony Rodari, Gilles Darcis, Carine Van Lint
Summary: The shock-and-kill strategy relies on latency reversing agents (LRAs) to reactivate HIV-1 and induce immune responses or cytopathic effects for elimination of latent virus. LRAs, particularly immunomodulatory ones, show potential for controlling HIV transcription pathways, but the precise mechanisms are not fully understood, complicating efforts to develop more efficient and safer cure strategies. Deciphering these mechanisms is crucial in designing approaches to eliminate latent HIV infection.
SEMINARS IN IMMUNOLOGY
(2021)
Article
Immunology
Min Li, Marietta M. Budai, Min Chen, Jin Wang
Summary: The study presents a strategy called selective elimination of host cells harboring replication-competent HIV (SECH) that targets HIV-1 reservoirs through inhibition of autophagy and promotion of apoptosis. This strategy has been shown to effectively clear latent HIV-1 reservoirs in different subsets of T cells. The findings provide a potential method for eradicating HIV-1 infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Mohsen Sheykhhasan, Aidin Foroutan, Hamed Manoochehri, Saeideh Gholamzadeh Khoei, Naresh Poondla, Massoud Saidijam
Summary: HIV/AIDS remains a major global public health issue, with gene therapy showing promising results in combating HIV infection. Traditional treatment methods have limitations and side effects, making gene therapy an effective alternative.
Article
Biochemistry & Molecular Biology
Mohammad Aqueel Khan, Sanjeev Kumar Singh
Summary: The study focuses on HIV-1 latency and its role in hindering the eradication of HIV-1 infection. Using an atom-based 3D-QSAR model, the researchers aim to understand the structural requirements for developing potent HIV-1 latency reversal agents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Microbiology
Anthony Rodari, Gilles Darcis, Carine M. Van Lint
Summary: cART effectively reduces HIV-1 replication but cannot cure the infection due to the persistence of stable HIV-1-infected cellular reservoirs, leading to viral rebound upon cART interruption. The shock and kill strategy aims to reactivate latent viral gene expression and eliminate infected cells to reduce the size of the HIV-1 reservoir. Different classes of latency reversing agents (LRAs) have been studied to improve reactivation of viral gene expression, and combining multiple LRAs simultaneously or sequentially may optimize the shock strategy.
ANNUAL REVIEW OF VIROLOGY, VOL 8
(2021)
Review
Biochemistry & Molecular Biology
Annika P. Schnell, Stephan Kohrt, Andrea K. Thoma-Kress
Summary: HTLV-1, a retrovirus infecting CD4(+) T-cells and causing ATLL, evades efficient CTL responses by repressing viral gene expression. Therapeutic strategies aim to transiently activate viral gene expression and antigen presentation to enhance CTL responses and expose the latent HTLV-1 reservoir. LRAs like HDACi and P-TEFb activators, studied in the context of HIV, may also be effective against HTLV-1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Sushant Khanal, Madison Schank, Mohamed El Gazzar, Jonathan P. Moorman, Zhi Q. Yao
Summary: Eradication of latent HIV infection is a global health challenge, with popular strategies for HIV cure involving reactivation and killing of virus-infected cells. While antiretroviral therapy can halt HIV replication, it cannot completely eliminate latent proviruses, leading to reservoirs of infection that can cause cellular and systemic complications in HIV patients despite lack of active viral production. Studies into the mechanisms of HIV latency and reservoir formation are crucial for identifying strategies to eliminate viral reservoirs and ultimately cure HIV infection.
Article
Multidisciplinary Sciences
Alice Cho, Christian Gaebler, Thiago Olveira, Victor Ramos, Marwa Saad, Julio C. C. Lorenzi, Anna Gazumyan, Susan Moir, Marina Caskey, Tae-Wook Chun, Michel C. Nussenzweig
Summary: HIV-1 infection leads to the formation of a long-lasting reservoir of latently infected CD4(+) T cells, consisting of intact and defective proviruses. This study used Q4PCR to quantify the reservoir content and found that the defective reservoir remained stable while the intact proviral reservoir decayed over time. Both the intact and defective proviral reservoirs showed dynamic changes, with an enrichment of intact proviruses in expanded CD4(+) T cell clones and a decrease in overall reservoir complexity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biotechnology & Applied Microbiology
Preethi B. Balakrishnan, Carissa S. Holmberg, Debbie K. Ledezma, Alberto Bosque, Rohan Fernandes
Summary: This study investigates the use of nanoparticles as carriers to deliver drugs for the reactivation of latent HIV infection. The results show that polymeric-coated nanoparticles are more effective than free polymers in activating latent HIV and enhancing immune activation.
Review
Virology
Gerard Campos-Gonzalez, Javier Martinez-Picado, Talia Velasco-Hernandez, Maria Salgado
Summary: Chimeric antigen receptor (CAR) technology has had a significant impact on the treatment of blood malignancies, particularly various types of leukemia. However, applying this technology to HIV treatment presents numerous challenges that hinder its widespread adoption.
Review
Chemistry, Medicinal
Juliana Romano Lopes, Diego Eidy Chiba, Jean Leandro Dos Santos
Summary: The challenge of curing all HIV patients lies in eliminating the latent reservoir of the virus, with the 'kick-and-kill' approach showing promise but facing limitations in current latency reversal agents. Complete depletion of the latent virus reservoir is crucial for achieving this goal.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Medicine, General & Internal
Silvere D. Zaongo, Yue Wang, Ping Ma, Fang-Zhou Song, Yao-Kai Chen
Summary: Recent research has introduced a promising alternative therapeutic option for HIV/AIDS, known as selective elimination of host cells capable of producing HIV (SECH). This approach requires the simultaneous administration of drugs targeting specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. However, there are still three major challenges that may restrict the application of the SECH strategy in HIV/AIDS patients.
CHINESE MEDICAL JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Mizushi Yanagihara, Naoki Kishimoto, Kanae Nakahara, Towa Abe, Satoshi Miura, Bangzhong Lin, Megumi Fumimoto, Junichi Haruta, Shogo Misumi, Mitsuhiro Arisawa, Kenichi Murai
Summary: Structurally simplified analogues of ansellone A were synthesized by replacing the decalin skeleton with a lipophilic chain, and their HIV latency-reversing activities were evaluated. Two analogues with ether and alkenyl side chains showed comparable activities to ansellone A. The simplified compounds were easily synthesized using Prins cyclisation chemistry.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Plant Sciences
Haitao Zhang, Jinfeng Cai, Chunna Li, Lisi Deng, Hongqiong Zhu, Ting Huang, Jiacong Zhao, Jiasheng Zhou, Kai Deng, Zhongsi Hong, Jinyu Xia
Summary: This study found that wogonin can suppress latent HIV-1 reactivation by inhibiting the expression of histone acetyltransferase p300 and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. This discovery holds promising significance for future applications in HIV-1 functional cure.
Article
Biochemistry & Molecular Biology
Joelma M. M. Sarturi, Luciano Dornelles, Natalia V. V. Segatto, Tiago Collares, Fabiana K. K. Seixas, Bruna Candia Piccoli, Fernanda D'Avila da Silva, Folorunsho Bright Omage, Joao Batista Teixeira da Rocha, Renata A. A. Balaguez, Diego Alves, Eder J. J. Lenardao, Eric F. F. Lopes, Anna Kula-Pacurar, Krzysztof Pyrc, Luca Sancineto, Oscar E. D. Rodrigues
Summary: This study synthesized and evaluated the multi-target behavior of new 5'-hydroxy-3-(chalcogenyl-triazoyl)-thymidine derivatives as antioxidant and anti-HIV agents. The compounds showed good activity and no apparent toxicity in mice. The design strategy of modifying the AZT nucleus via the 1,3-dipolar Huisgen cycloaddition reaction proved effective in achieving the desired biological activities.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Luxsena Sukumaran, Ken M. Kunisaki, Nicholas Bakewell, Alan Winston, Patrick W. G. Mallon, Nicki Doyle, Jane Anderson, Marta Boffito, Lewis Haddow, Frank A. Post, Jaime H. Vera, Memory Sachikonye, Caroline A. Sabin
Summary: HIV patients have a higher risk of cardiovascular diseases, which may be attributed to inflammation and immune activation. Three distinct inflammatory profiles were identified, and their associations with cardiovascular disease risk were assessed. The results showed that HIV patients with gut/immune activation and neurovascular inflammation profiles had higher cardiovascular disease risk compared to those with relatively low inflammation.
Article
Endocrinology & Metabolism
Neil E. Wrigley Kelly, Conor De Barra, Ferrah Shaamile, Aisling Holland, Liam Shaw, Patrick W. G. Mallon, Jean O'Connell, Andrew E. Hogan, Donal O'Shea
Summary: People with obesity who have completed a primary course of ChAdOx1 COVID-19 vaccination have robust, durable, and functional antigen-specific T cell immunity that is comparable to that seen in people without obesity.
INTERNATIONAL JOURNAL OF OBESITY
(2023)
Review
Immunology
Rachel MacCann, Alan L. L. Landay, Patrick W. G. Mallon
Summary: The article reviews alterations in microbiota composition, diversity, and functional features in relation to chronic inflammation and comorbidities associated with HIV infection. The gut microbiome plays a crucial role in host immunity, and disruption of gut homeostasis can lead to systemic inflammation and immune activation. Ageing and HIV share similar features of intestinal damage and changes in bacterial composition, contributing to a proinflammatory state and age-related comorbidities. The nicotinamide adenine dinucleotide (NAD+)-producing kynurenine pathway (KP) is explored as a potential inflammatory pathway involved in metabolic changes and age-related diseases in PWH.
CURRENT OPINION IN HIV AND AIDS
(2023)
Review
Medicine, General & Internal
Areti Angeliki Veroniki, Andrea C. Tricco, Jennifer Watt, Sofia Tsokani, Paul A. Khan, Charlene Soobiah, Ahmed Negm, Amanda Doherty-Kirby, Paul Taylor, Carole Lunny, Jessie McGowan, Julian Little, Patrick Mallon, David Moher, Sabrina Wong, Jacqueline Dinnes, Yemisi Takwoingi, Lynora Saxinger, Adrienne Chan, Wanrudee Isaranuwatchai, Bryn Lander, Adrienne Meyers, Guillaume Poliquin, Sharon E. Straus
Summary: This study aimed to determine the most sensitive and specific rapid test for the diagnosis of SARS-CoV-2 through a rapid review and diagnostic test accuracy network meta-analysis. The results showed that rapid molecular tests had high sensitivity and specificity, while rapid antigen tests were mainly associated with high specificity.
Article
Biotechnology & Applied Microbiology
Kevin Purves, Ruth Haverty, Tiina O'Neill, David Folan, Sophie O'Reilly, Alan W. Baird, Dimitri Scholz, Patrick W. Mallon, Virginie Gautier, Michael Folan, Nicola F. Fletcher
Summary: ViruSAL, a novel proprietary formulation, has been shown to effectively inhibit diverse enveloped viral infections in vitro and in vivo. In this study, we evaluated the ability of ViruSAL to inhibit SARS-CoV-2 infectivity using physiologically relevant models of the human bronchial epithelium. Our results demonstrated that ViruSAL potently inhibited SARS-CoV-2 infection in a concentration- and time-dependent manner in bronchial airway models. Importantly, ViruSAL also showed inhibitory effects on viral infection when added post-infection, without causing cellular toxicity. Additionally, intranasal instillation of ViruSAL in a rat model did not lead to any toxicity or pathological changes.
JOURNAL OF GENERAL VIROLOGY
(2023)
Review
Virology
Estelle Plant, Maxime Bellefroid, Carine Van Lint
Summary: Bovine Leukemia Virus (BLV) is the cause of enzootic bovine leukosis, which is characterized by the proliferation of B cells in cattle. BLV has the ability to remain dormant in the host, evade the immune system, and promote tumor development. This review summarizes the molecular mechanisms regulating BLV transcription units, including cis-regulatory elements and epigenetic modifications. It also discusses the role of BLV miRNAs and antisense transcripts in tumorigenesis and the relevance of BLV as a model for studying HTLV-1.
Editorial Material
Immunology
Patrick W. G. Mallon
CURRENT OPINION IN HIV AND AIDS
(2023)
Editorial Material
Immunology
Alexander O. O. Pasternak, Olivier Rohr, Carine Van Lint, Anna Kula-Pacurar
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Correction
Immunology
Alexander O. Pasternak, Olivier Rohr, Carine Van Lint, Anna Kula-Pacurar
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Immunology
Rachel MacCann, Alejandro Abner Garcia Leon, Gabriel Gonzalez, Michael J. Carr, Eoin R. Feeney, Obada Yousif, Aoife G. Cotter, Eoghan de Barra, Corinna Sadlier, Peter Doran, Patrick W. Mallon
Summary: This study suggests that early host immune responses, including defects in mast cell activation and interferon responses, are associated with more severe outcomes in COVID-19. Understanding this pathway could lead to better treatments for vulnerable individuals.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Grace Kenny, Liam Townsend, Stefano Savinelli, Patrick W. G. Mallon
Summary: The emergence of persistent ill-health in the aftermath of SARS-CoV-2 infection has presented significant challenges. The symptoms of long COVID are highly variable and the underlying pathophysiology remains poorly understood. Current potential therapies are being investigated, but no proven effective treatment exists.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Infectious Diseases
Jessica Doctor, Alan Winston, Jaime H. Vera, Frank A. Post, Marta Boffito, Patrick W. G. Mallon, Jane Anderson, Christina Prechtl, Ian Williams, Margaret Johnson, Emmanouil Bagkeris, Memory Sachikonye, Caroline A. Sabin, POPPY Study
Summary: This study investigates the association between the use of anticholinergic medications (ACMs) and recurrent falls and frailty in people with HIV. The results show that ACM users have a higher incidence of recurrent falls and frailty compared to non-users. Therefore, clinicians should be aware of this and aim to reduce the use of ACMs.
Review
Virology
Nicolas Lambert, Majdouline El Moussaoui, Frederic Baron, Pierre Maquet, Gilles Darcis
Summary: Opportunistic viral infections of the central nervous system are a significant cause of morbidity and mortality among immunocompromised patients. Antiviral treatments are usually ineffective, so the prognosis depends on timely immune reconstitution. Virus-specific T-cells are increasingly being recognized as a valuable tool to treat these infections, and have potential applications in the treatment of progressive multiple sclerosis and EBV-associated central nervous system inflammatory disease. The key future milestones of this treatment strategy are also discussed.
Article
Microbiology
Gilles Vossius, Cecile Meex, Filip Moerman, Marie Thys, Marie Ernst, Marie-Eve Bourgeois, Lea Wagner, Thibaut Delahaye, Gilles Darcis
Summary: The study aimed to assess the impact of third-generation cephalosporins (3GCs) vs. alternative antibiotics on clinical outcomes in bloodstream infections (BSIs) due to AmpC-inducible Enterobacterales (AmpC-E). The findings suggest that 3GC definitive therapy may not result in poorer clinical outcomes for the treatment of BSIs caused by AmpC-E.