Article
Veterinary Sciences
Kimberly Schmitt, James Curlin, Leila Remling-Mulder, Jared Morrison, Ryan Moriarty, Kelly Goff, Mark Stenglein, Shelby O'Connor, Preston Marx, Ramesh Akkina
Summary: Using humanized mice, researchers observed the evolution of SIV chimpanzee into HIV-1 Group M, with higher viral load, increased CD4(+) T-cell decline, and nonsynonymous substitutions indicating viral evolution.
JOURNAL OF MEDICAL PRIMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Prasanta K. Dash, Chen Chen, Rafal Kaminski, Hang Su, Pietro Mancuso, Brady Sillman, Chen Zhang, Shuren Liao, Sruthi Sravanam, Hong Liu, Emiko Waight, Lili Guo, Saumi Mathews, Rahsan Sariyer, R. Lee Mosley, Larisa Y. Poluektova, Maurizio Caocci, Shohreh Amini, Santhi Gorantla, Tricia H. Burdo, Benson Edagwa, Howard E. Gendelman, Kamel Khalili
Summary: Treatment of HIV-1ADA-infected CD34+ NSG-humanized mice with long-acting ester prodrugs of cabotegravir, lamivudine, and abacavir in combination with native rilpivirine followed by dual CRISPR-Cas9 editing of CCR5 and HIV-1 proviral DNA led to elimination of replication-competent virus in 58% of infected mice and restoration of human CD4+ T cell numbers. The dual CRISPR therapy demonstrated statistically significant improvements in HIV-1 cure percentages compared to single treatments. Rating: 9/10
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Shawn Abeynaike, Silke Paust
Summary: While HIV-1 infection can now be managed with lifelong treatment, complete eradication remains a challenge due to the virus's ability to remain in dormant state in tissue reservoirs and its high mutation rate. Developing a suitable animal model is critical for evaluating pathogenesis and therapeutic approaches for HIV-1 cure strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Mathieu Amand, Philipp Adams, Rafaela Schober, Gilles Iserentant, Jean-Yves Servais, Michel Moutschen, Carole Seguin-Devaux
Summary: HIV-1 infection leads to inflammasome activation, and inhibiting caspase-1 with VX-765 reduces immune activation, viral load, and HIV-1 reservoir formation. The study showed increased expression of caspase-1, NLRP3, IL-1 beta, IFI16, and AIM2 after HIV-1 infection. Treatment with VX-765 significantly reduced TNF-alpha, IL-18, CD4(+) T cells, viral load, and HIV-1 DNA in the spleen.
Article
Medicine, Research & Experimental
Can M. Sungur, Qiankun Wang, Ayse N. Ozanturk, Hongbo Gao, Aaron J. Schmitz, Marina Cella, Wayne M. Yokoyama, Liang Shan
Summary: The role of NK cells in HIV-1 infections was investigated using a humanized mouse model. The study showed that NK cells directly provided anti-HIV-1 responses in nonlymphoid organs, but had limited functionality in lymphoid organs. Antiretroviral therapy and a broadly neutralizing antibody, PGT121, were found to enhance NK cell function and reduce viral load.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Veterinary Sciences
James Z. Curlin, Kimberly Schmitt, Leila Remling-Mulder, Corina Valencia Tibbitts, Shelby O'Connor, Preston Marx, Ramesh Akkina
Summary: HIV-1 originated from SIVcpz and evolved in humans. Humanized mice prove to be an effective tool for studying viral evolution by measuring viral loads, analyzing CD4(+) T cell decline, and observing genetic changes. Through four serial passages, numerous non-synonymous mutations were identified, which play a crucial role in the adaptation and evolution of SIVcpz to human immune cells.
JOURNAL OF MEDICAL PRIMATOLOGY
(2023)
Review
Microbiology
Chen Zhang, Lubaba A. Zaman, Larisa Y. Poluektova, Santhi Gorantla, Howard E. Gendelman, Prasanta K. Dash
Summary: The persistence of latent viral infections in HIV-1 infected individuals is a major obstacle to finding a cure. The identification of latent viral reservoirs is limited by their low abundance, the difficulty in accurately identifying latently infected cells, and the lack of biomarkers for identifying latent cells. Humanized mouse models are valuable tools for studying viral persistence and latency, as they can replicate the host cells and tissue environments that carry latent infections. These models can be used to test antiretroviral and excision therapeutics to address the detection and elimination of HIV-1 latency.
Article
Biology
Ting Guo, Qi Deng, Zhipeng Qiu, Libin Rong
Summary: Despite years of cART, HIV persists and rebounds in infected individuals, and the sources contributing to viral persistence and rebound are not fully understood. This study used HIV infection models to fit viral load data in treated and untreated humanized mice, and found that the loss of infected CD4+ T cells and macrophages contributes to viral decay, and latent infection of CD4+ T cells may cause the last phase of viral decay. Furthermore, the study suggests that pre-ART viral load and latent reservoir size can affect viral growth rate and predict the time to rebound, and early and prolonged cART can delay viral rebound after treatment cessation.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Virology
Maarja Gruenbach, Christina K. S. Muller, Erika Schlaepfer, Luca Baroncini, Doris Russenberger, Nicole P. Kadzioch, Benjamin Escher, Martin Schlapschy, Arne Skerra, Simon Bredl, Roberto F. Speck
Summary: The research explored the efficacy of novel, long-acting IFN-alpha 14 in controlling HIV replication in HIV-infected humanized mice. The study found that IFN-alpha 14 had no effect on chronic HIV infection but demonstrated a transiently restored responsiveness to IFN and a temporary lower HIV burden after stopping cART when mice were treated with cART first. These findings emphasize the value of cART-mediated HIV suppression and immune reconstitution in creating a window of opportunity for exploring novel immunotherapies, the potential of IFNs for constraining HIV, and the value of humanized mice for exploring novel immunotherapies.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Wenli Mu, Anjie Zhen, Mayra A. Carrillo, Valerie Rezek, Heather Martin, Miguel Lizarraga, Scott Kitchen
Summary: The HIV-1 pandemic continues to spread globally, and developing a cure strategy for HIV infection is crucial. Humanized mouse models have been developed to mimic HIV-1 infection and study potential treatments. However, current administration of antiretroviral therapy to the animals is ineffective, difficult, or unsafe. This article describes a novel oral cART method that successfully suppresses viral replication and improves the overall health of HIV-1 infected humanized mice.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Medicine, General & Internal
Yufei Mo, Ming Yue, Lok Yan Yim, Runhong Zhou, Chunhao Yu, Qiaoli Peng, Ying Zhou, Tsz-Yat Luk, Grace Chung-Yan Lui, Huarong Huang, Chun Yu Hubert Lim, Hui Wang, Li Liu, Hongzhe Sun, Jun Wang, Youqiang Song, Zhiwei Chen
Summary: The study found that nicotinamide mononucleotide (NMN) can modulate CD4+ T cell activation and suppress viral replication during HIV-1 infection. This discovery may provide a basis for the potential use of NMN in combination with antiretroviral therapy (ART) as a treatment option.
Article
Immunology
Matthew T. Ollerton, Joy M. Folkvord, Kristina K. Peachman, Soumya Shashikumar, Elaine B. Morrison, Linda L. Jagodzinski, Sheila A. Peel, Mohammad Khreiss, Richard T. D'Aquila, Sofia Casares, Mangala Rao, Elizabeth Connick
Summary: Humanized DRAGA mice can generate virus-specific antibodies in HIV-1 infection, but their support for germinal center responses is limited.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Philipp Adams, Virginie Fievez, Rafaela Schober, Mathieu Amand, Gilles Iserentant, Sofie Rutsaert, Geraldine Dessilly, Guido Vanham, Fanny Hedin, Antonio Cosma, Michel Moutschen, Linos Vandekerckhove, Carole Seguin-Devaux
Summary: CD32 may label highly activated/exhausted memory CD4(+) T-cell subsets that contain only a small proportion of the translation-competent reservoir.
Article
Microbiology
Jonathan M. O. Rawson, Olga A. Nikolaitchik, Jennifer A. Yoo, Xayathed Somoulay, Matthew A. Brown, Franck S. Mbuntcha Bogni, Vinay K. Pathak, Ferri Soheilian, Ryan L. Slack, Stefan G. Sarafianos, Wei-Shau Hu
Summary: Novel retroviruses can emerge from recombination between distantly related retroviruses. These recombinants may initially have replication defects, but they can adapt and enhance their replication by acquiring substitutions.
Article
Microbiology
Zhe Zhao, Riku Fagerlund, Helena Tossavainen, Kristina Hopfensperger, Rishikesh Lotke, Smitha Srinivasachar Badarinarayan, Frank Kirchhoff, Perttu Permi, Kei Sato, Daniel Sauter, Kalle Saksela
Summary: The accessory protein Nef of HIV and SIV interacts with cellular protein kinases and signaling proteins through a canonical SH3 binding motif. The study shows that Nef proteins have evolved a structural strategy called the R-clamp to facilitate salt bridge formation. Evolutionarily diverse Nef proteins exhibit different R-clamp designs, indicating a high level of diversity in the evolution of primate lentiviral proteins.
Article
Veterinary Sciences
James Curlin, Kimberly Schmitt, Leila Remling-Mulder, Ryan Moriarty, Mark Stenglein, Shelby O'Connor, Preston Marx, Ramesh Akkina
JOURNAL OF MEDICAL PRIMATOLOGY
(2020)
Article
Veterinary Sciences
James Curlin, Kimberly Schmitt, Leila Remling-Mulder, Ryan Moriarty, Kelly Goff, Shelby O'Connor, Mark Stenglein, Preston Marx, Ramesh Akkina
JOURNAL OF MEDICAL PRIMATOLOGY
(2020)
Article
Veterinary Sciences
Kimberly Schmitt, James Curlin, Leila Remling-Mulder, Ryan Moriarty, Kelly Goff, Shelby O'Connor, Mark Stenglein, Preston Marx, Ramesh Akkina
JOURNAL OF MEDICAL PRIMATOLOGY
(2020)
Article
Veterinary Sciences
Kimberly Schmitt, James Curlin, Leila Remling-Mulder, Jared Morrison, Ryan Moriarty, Kelly Goff, Mark Stenglein, Shelby O'Connor, Preston Marx, Ramesh Akkina
Summary: Using humanized mice, researchers observed the evolution of SIV chimpanzee into HIV-1 Group M, with higher viral load, increased CD4(+) T-cell decline, and nonsynonymous substitutions indicating viral evolution.
JOURNAL OF MEDICAL PRIMATOLOGY
(2022)
Article
Veterinary Sciences
James Z. Curlin, Kimberly Schmitt, Leila Remling-Mulder, Jared Morrison, John J. Baczenas, Corina Valencia Tibbits, Kelly Goff, Shelby O'Connor, Mark Stenglein, Preston Marx, Ramesh Akkina
Summary: Serial passage of SIVmac239 enables a better understanding of the genetic changes required for cross-species transmission of primate lentiviruses to humans. Using humanized mice, it is shown that adaptive mutations continue to accumulate in SIVmac239 during four consecutive passages, leading to persistent decline of CD4(+) T cells and increased plasma viral loads.
JOURNAL OF MEDICAL PRIMATOLOGY
(2022)
Article
Immunology
Kimberly Schmitt, James Z. Curlin, Leila Remling-Mulder, Tawfik Aboellail, Ramesh Akkina
Summary: In this study, neonatal humanized mice were used to model congenital zika syndrome (CZS) and evaluate the viral effects on human hematopoietic stem cells. The mice exhibited symptoms of stunted growth, abnormal posture, ruffled fur, and ocular defects, along with gross pathologies in the brain and visceral organs. The study confirmed that ZIKV actively infected human CD34(+) hematopoietic stem cells and restricted the development of terminally differentiated B cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Veterinary Sciences
James Z. Curlin, Kimberly Schmitt, Leila Remling-Mulder, Corina Valencia Tibbitts, Shelby O'Connor, Preston Marx, Ramesh Akkina
Summary: HIV-2 Group F virus, originating from NHPs, was isolated from only two individuals. After two serial passages in hu-mice, increased viral loads, decline in CD4+ T cells, and nonsynonymous genetic changes were observed, indicating its potential for further evolution and spread in humans.
JOURNAL OF MEDICAL PRIMATOLOGY
(2023)
Article
Veterinary Sciences
James Z. Curlin, Kimberly Schmitt, Leila Remling-Mulder, Corina Valencia Tibbitts, Shelby O'Connor, Preston Marx, Ramesh Akkina
Summary: HIV-1 originated from SIVcpz and evolved in humans. Humanized mice prove to be an effective tool for studying viral evolution by measuring viral loads, analyzing CD4(+) T cell decline, and observing genetic changes. Through four serial passages, numerous non-synonymous mutations were identified, which play a crucial role in the adaptation and evolution of SIVcpz to human immune cells.
JOURNAL OF MEDICAL PRIMATOLOGY
(2023)