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
Multidisciplinary Sciences
Marcela Pavova, Paul Eduardo Reyes-Gutierrez, Jaroslav Kozak, Juraj Dobias, Yevgen Yurenko, Martin Lepsik, Filip Teply, Jan Weber
Summary: G-quadruplexes, which are nucleic acids containing quartets of guanines, play a role in regulating gene transcription. Helquat-based compounds have been identified as a new class of anti-HIV-1 inhibitors that can stabilize G-quadruplexes in the HIV-1 long-terminal repeat sequence. This discovery can contribute to the rational design of inhibitors targeting G-quadruplexes in HIV-1.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, General & Internal
Jonathan Herskovitz, Mahmudul Hasan, Milankumar Patel, Wilson R. Blomberg, Jacob D. Cohen, Jatin Machhi, Farah Shahjin, R. Lee Mosley, JoEllyn McMillan, Bhavesh D. Kevadiya, Howard E. Gendelman
Summary: The study developed a library of gRNAs designed to disrupt five HIV-1 exons, and validated their efficacy through various delivery methods. Results showed that multi-exon gRNA disruption delivered by LNPs enables effective excision of HIV-1.
Article
Virology
Savannah F. Pedersen, Jack A. Collora, Rachel N. Kim, Kerui Yang, Anya Razmi, Allison A. Catalano, Yang-Hui Jimmy Yeh, Karam Mounzer, Pablo Tebas, Luis J. Montaner, Ya-Chi Ho
Summary: This study identified SLTM as a novel host protein that regulates HIV-1 gene expression. Knocking down SLTM can reactivate HIV-1 and induce cell death in infected cells.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Huibao Feng, Jiahui Guo, Tianmin Wang, Chong Zhang, Xin-hui Xing
Summary: The CRISPR-Cas9 system has been widely used in biotechnological applications, but off-target effects remain a major concern. A study on sgRNA libraries in living bacteria cells revealed a synergistic effect in double mutations, and identified a specific mismatch type that caused only moderate impairment on binding affinity. A biophysical model was established to understand the causal relationship between mismatch and binding behavior of dCas9, which could be repurposed as a predictive tool for sgRNA design.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Xiao-Han Liu, Bang-Rui Li, Zhan-Ming Ying, Li-Juan Tang, Fenglin Wang, Jian-Hui Jiang
Summary: The study introduces a new concept of small-molecule-mediated split-aptamer assembly for inducible CRISPR-dCas9 transcription activation. It demonstrates the quantitative detection and imaging of S-adenosyl methionine (SAM) in live cells using this inducible transcription system.
ACS CHEMICAL BIOLOGY
(2022)
Review
Virology
Lori A. Emert-Sedlak, Haibin Shi, Colin M. Tice, Li Chen, John J. Alvarado, Sherry T. Shu, Shoucheng Du, Catherine E. Thomas, Jay E. Wrobel, Allen B. Reitz, Thomas E. Smithgall
Summary: This review focuses on the discovery of pharmacological inhibitors of the HIV-1 Nef accessory protein. Nef inhibitors not only suppress HIV-1 replication, but also restore sufficient MHC-I to the surface of infected cells to trigger a cytotoxic T lymphocyte response. Combining Nef inhibitors with other therapeutic approaches may provide a path to clearing viral reservoirs.
Review
Pharmacology & Pharmacy
Sepideh Saeb, Clementine Wallet, Olivier Rohr, Christian Schwartz, Thomas Loustau
Summary: Currently, combination antiretroviral therapy (cART) is the standard treatment for HIV-1. However, it cannot eliminate latent reservoirs of the virus, leading to lifelong treatment and drug resistance. Suppressing viral latency is the biggest challenge for HIV-1 eradication. This review examines the latest advances in epigenetic transformations involved in CNS viral latency and targeting of brain reservoirs, including evidence from clinical studies and in vitro models.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Immunology
Xiaofan Yang, Ting Huang, Tiantian Wang, Hongbo Gao, Haitao Zhang, Wen Peng, Jiacong Zhao, Shujing Hu, Panpan Lu, Zhongsi Hong, Bo Li, Kai Deng
Summary: This study demonstrates the critical role of MAT2A-mediated one-carbon metabolism in regulating HIV-1 latency. Knockout of MAT2A enhances the reactivation of latent HIV-1 by reducing DNA and histone methylation. Plasma SAM levels are positively correlated with HIV-1 DNA in PBMCs from ART-treated infected individuals, suggesting SAM could serve as a potential biomarker for the latent viral reservoir.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Awadh Alanazi, Andrey Ivanov, Namita Kumari, Xionghao Lin, Songping Wang, Dmytro Kovalskyy, Sergei Nekhai
Summary: This study identified a novel benzoxazole compound, T0516-4834, that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection, suggesting its potential as a new lead for anti-HIV-1 therapeutics.
Review
Virology
Josh G. Kim, Liang Shan
Summary: HIV-1 protease plays a critical role in the maturation of viral particles and can also cleave host cell proteins. The interaction between HIV-1 protease and CARD8 inflammasome is of particular interest, as recent studies have shown that CARD8 can sense the activity of HIV-1 protease and induce cell death. Premature activation of HIV-1 protease may be used as a strategy to target CARD8-mediated cell killing and eliminate latent reservoirs in people living with HIV.
Article
Immunology
Poonam Suryawanshi, Rajani Bagul, Ashwini Shete, Madhuri Thakar
Summary: The study demonstrated that HIV-1 Env could serve as a latency reversal agent (LRA), and only ADCC mediating antibodies were able to kill the reactivated HIV reservoirs. The findings have implications in designing antibody-mediated immunotherapy for eradicating latent HIV reservoir.
FRONTIERS IN IMMUNOLOGY
(2021)
Editorial Material
Immunology
Brianna Lopez, Robert F. Siliciano
Summary: The latent reservoir for HIV-1, which hinders a cure, is challenging to study due to the scarcity of latently infected cells and the absence of distinctive markers. Sun et al. used single cell analysis of T cell surface phenotypes to demonstrate the immune selection of reservoir cells.
TRENDS IN IMMUNOLOGY
(2023)
Article
Oncology
Guanhua Wu, Qi Wang, Da Wang, Fei Xiong, Wenzheng Liu, Junsheng Chen, Bing Wang, Wenhua Huang, Xin Wang, Yongjun Chen
Summary: Cholangiocarcinoma (CCA) has shown increased expression of EZH2, SUZ12, and EED, leading to elevated levels of H3K27me3. Targeting polycomb repressor complex 2 (PRC2) can remove H3K27me3 from the secreted frizzled-related protein 1 (SFRP1) promoter, inducing DNA hypomethylation and activating SFRP1 transcription. Inhibiting PRC2, including EZH2 inhibitors like GSK343, holds promise as a potential strategy for developing anti-cancer drugs for CCA.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Sarah Klinnert, Alex Chemnitzer, Peter Rusert, Karin J. Metzner
Summary: CRISPR/dCas9-based activation systems have shown promise in reversing HIV-1 latency. In this study, the dCas9-VPR system was evaluated and the optimal gRNA target site in the HIV-1 5'LTR promoter was identified. The results demonstrated that the dCas9-VPR system can effectively activate HIV-1 and the optimal activation region is located -165 to -106 bp from the transcription start site.
JOURNAL OF GENERAL VIROLOGY
(2022)
Article
Microbiology
Gabriele Cerutti, Yicheng Guo, Tongqing Zhou, Jason Gorman, Myungjin Lee, Micah Rapp, Eswar R. Reddem, Jian Yu, Fabiana Bahna, Jude Bimela, Yaoxing Huang, Phinikoula S. Katsamba, Lihong Liu, Manoj S. Nair, Reda Rawi, Adam S. Olia, Pengfei Wang, Baoshan Zhang, Gwo-Yu Chuang, David D. Ho, Zizhang Sheng, Peter D. Kwong, Lawrence Shapiro
Summary: Structural analysis revealed that seven potent NTD-directed neutralizing antibodies target a common surface on NTD, forming a single supersite different from the recognition pattern of RBD-directed antibodies.
CELL HOST & MICROBE
(2021)
Article
Multidisciplinary Sciences
Pengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, Barney S. Graham, John R. Mascola, Jennifer Y. Chang, Michael T. Yin, Magdalena Sobieszczyk, Christos A. Kyratsous, Lawrence Shapiro, Zizhang Sheng, Yaoxing Huang, David D. Ho
Summary: The COVID-19 pandemic has had global repercussions, with promising vaccines and monoclonal antibody therapies. However, newly detected variants of SARS-CoV-2 present challenges to these treatment options.
Article
Cardiac & Cardiovascular Systems
Liuliu Yang, Yuling Han, Fabrice Jaffre, Benjamin E. Nilsson-Payant, Yaron Bram, Pengfei Wang, Jiajun Zhu, Tuo Zhang, David Redmond, Sean Houghton, Skyler Uhl, Alain Borczuk, Yaoxing Huang, Chanel Richardson, Vasuretha Chandar, Joshua A. Acklin, Jean K. Lim, Zhengming Chen, Jenny Xiang, David D. Ho, Benjamin R. tenOever, Robert E. Schwartz, Todd Evans, Shuibing Chen
Summary: Cardiac complications in COVID-19 patients are commonly associated with macrophage-mediated inflammation. The study established an immunocardiac coculture platform to model this inflammation, identifying potential drug candidates like ranolazine and tofacitinib that protect cardiomyocytes from macrophage-induced damage.
CIRCULATION RESEARCH
(2021)
Article
Multidisciplinary Sciences
Alberto Bartolome, Jiani Liang, Pengfei Wang, David D. Ho, Utpal B. Pajvani
Summary: ACE2 is both a key regulator of the renin-angiotensin system and the functional receptor of SARS-CoV-2. Research suggests that it may be affected by gamma S proteolytic activity, leading to a novel pathway for cellular ACE2 trafficking.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Micah Rapp, Yicheng Guo, Eswar R. Reddem, Jian Yu, Lihong Liu, Pengfei Wang, Gabriele Cerutti, Phinikoula Katsamba, Jude S. Bimela, Fabiana A. Bahna, Seetha M. Mannepalli, Baoshan Zhang, Peter D. Kwong, Yaoxing Huang, David D. Ho, Lawrence Shapiro, Zizhang Sheng
Summary: Antibodies derived from the VH1-2 gene have been shown to be potent neutralizing antibodies against SARS-CoV-2, with three VH1-2-derived antibodies (2-15, 2-43, and H4) using VH1-2-encoded motifs to recognize the receptor-binding domain (RBD) of the virus spike protein. Despite genetic similarities, these antibodies are able to recognize both up and down conformations of the RBD, with some antibodies using elongated CDRH3s to interact with glycan N343 on a neighboring RBD. The VH1-2 antibody class utilizes modular genetic elements for modular recognition, with VH gene specifying RBD recognition and CDRH3 specifying quaternary interactions.
Article
Engineering, Chemical
Bharat Madan, Eswar R. Reddem, Pengfei Wang, Ryan G. Casner, Manoj S. Nair, Yaoxing Huang, Ahmed S. Fahad, Matheus Oliveira de Souza, Bailey B. Banach, Sheila N. Lopez Acevedo, Xiaoli Pan, Rajani Nimrania, I-Ting Teng, Fabiana Bahna, Tongqing Zhou, Baoshan Zhang, Michael T. Yin, David D. Ho, Peter D. Kwong, Lawrence Shapiro, Brandon J. DeKosky
Summary: Screening for anti-SARS-CoV-2 mAbs at reduced pH can lead to more efficient neutralizing antibody discovery, and a potent new antibody LP5 targets the SARS-CoV-2 N-terminal domain via a unique binding recognition mode.
Article
Multidisciplinary Sciences
Medini K. Annavajhala, Hiroshi Mohri, Pengfei Wang, Manoj Nair, Jason E. Zucker, Zizhang Sheng, Angela Gomez-Simmonds, Anne L. Kelley, Maya Tagliavia, Yaoxing Huang, Trevor Bedford, David D. Ho, Anne-Catrin Uhlemann
Summary: The emergence of the B.1.526 lineage of SARS-CoV-2, with mutations such as E484K, has led to its rapid dominance in New York City. This variant is resistant to therapeutic monoclonal antibodies and less susceptible to neutralization by antibodies from recovered or vaccinated individuals, contributing to its fast spread.
Article
Multidisciplinary Sciences
Jianliang Xu, Kai Xu, Seolkyoung Jung, Andrea Conte, Jenna Lieberman, Frauke Muecksch, Julio Cesar Cetrulo Lorenzi, Solji Park, Fabian Schmidt, Zijun Wang, Yaoxing Huang, Yang Luo, Manoj S. Nair, Pengfei Wang, Jonathan E. Schulz, Lino Tessarollo, Tatsiana Bylund, Gwo-Yu Chuang, Adam S. Olia, Tyler Stephens, I-Ting Teng, Yaroslav Tsybovsky, Tongqing Zhou, Vincent Munster, David D. Ho, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig, Peter D. Kwong, Rafael Casellas
Summary: The study found that camelid nanobodies can effectively circumvent vaccine escape caused by mutations in the novel coronavirus. These nanobodies are able to neutralize SARS-CoV-2 variants through two mechanisms, demonstrating promising potential in preventing COVID-19 mortality when vaccines are compromised.
Article
Cell Biology
Xiaohua Duan, Xuming Tang, Manoj S. Nair, Tuo Zhang, Yunping Qiu, Wei Zhang, Pengfei Wang, Yaoxing Huang, Jenny Xiang, Hui Wang, Robert E. Schwartz, David D. Ho, Todd Evans, Shuibing Chen
Summary: Developing disease models to study SARS-CoV-2 infection is crucial, and research using airway organoids derived from human pluripotent stem cells has identified compounds that can block the virus. Further investigation reveals that these compounds inhibit SARS-CoV-2 infection by targeting the HIF1a-glycolysis axis.
Article
Immunology
Pengfei Wang, Ryan G. Casner, Manoj S. Nair, Jian Yu, Yicheng Guo, Maple Wang, Jasper F-W Chan, Gabriele Cerutti, Sho Iketani, Lihong Liu, Zizhang Sheng, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Yaoxing Huang, Lawrence Shapiro, David D. Ho
Summary: The development of potent and broad-spectrum antiviral therapeutics and vaccines is crucial in dealing with highly pathogenic human coronaviruses and their evolving variants. Monoclonal antibody 2-36, isolated from COVID-19-convalescent patients, has been found to cross-neutralize SARS-CoV and other coronaviruses. The cryo-EM structure of 2-36 with SARS-CoV-2 and SARS-CoV spike reveals a conserved epitope in the receptor-binding domain (RBD). This antibody can neutralize various SARS-CoV-2 variants, as well as bat and pangolin sarbecoviruses that use human ACE2 as a receptor.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Immunology
Xun Wang, Xiaoyu Zhao, Jieyu Song, Jing Wu, Yuqi Zhu, Minghui Li, Yuchen Cui, Yanjia Chen, Lulu Yang, Jun Liu, Huanzhang Zhu, Shibo Jiang, Pengfei Wang
Summary: This study found that the Omicron variant is highly resistant to neutralization by sera from convalescents or individuals vaccinated with two doses of inactivated whole-virion vaccines. However, a homologous or heterologous booster significantly increased neutralization titers. Additionally, the Omicron variant resists most monoclonal antibodies targeting distinct epitopes. These findings highlight the importance of pushing forward booster vaccinations to combat emerging SARS-CoV-2 variants.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Microbiology
Jingwen Ai, Xun Wang, Xinyi He, Xiaoyu Zhao, Yi Zhang, Yuchao Jiang, Minghui Li, Yuchen Cui, Yanjia Chen, Rui Qiao, Lin Li, Lulu Yang, Yi Li, Zixin Hu, Wenhong Zhang, Pengfei Wang
Summary: This study compared the neutralization efficacy of vaccine-induced or monoclonal antibodies against different sub-lineages of the Omicron variant. The results showed that current vaccines have low neutralization activity, but both homologous and heterologous boosters significantly improved neutralization titers. The study also found that most monoclonal antibodies lost their neutralizing activity, while some demonstrated distinct neutralization patterns among Omicron sub-lineages, indicating antigenic differences.
CELL HOST & MICROBE
(2022)
Review
Microbiology
Hao Zhou, Michelle Mohlenberg, Jigarji C. Thakor, Hardeep Singh Tuli, Pengfei Wang, Yehuda G. Assaraf, Kuldeep Dhama, Shibo Jiang
Summary: The SARS-CoV-2 virus is continuously evolving and mutating, with the emergence of the highly mutated and transmissible Omicron variant. This variant evades protection from vaccines and antibody-based therapies, but is sensitive to certain antiviral drugs. Understanding the virology and immune mechanisms of the Omicron variant is crucial for developing effective vaccines and treatments.
CLINICAL MICROBIOLOGY REVIEWS
(2022)
Article
Microbiology
Xun Wang, Minghui Li, Panpan Lu, Chen Li, Chaoyue Zhao, Xiaoyu Zhao, Rui Qiao, Yuchen Cui, Yanjia Chen, Jiayan Li, Guonan Cai, Pengfei Wang
Summary: There are concerns about the safety of SARS-CoV-2 vaccines and antibody therapeutics due to evidence of antibody-dependent enhancement (ADE) of other viruses. In this study, it was found that vaccination/convalescent sera and certain monoclonal antibodies can enhance SARS-CoV-2 infection in vitro. However, this enhancement can be prevented by blocking the interaction between antibodies and receptors.
Article
Multidisciplinary Sciences
Yuling Han, Xiaohua Duan, Liuliu Yang, Benjamin E. Nilsson-Payant, Pengfei Wang, Fuyu Duan, Xuming Tang, Tomer M. Yaron, Tuo Zhang, Skyler Uhl, Yaron Bram, Chanel Richardson, Jiajun Zhu, Zeping Zhao, David Redmond, Sean Houghton, Duc-Huy T. Nguyen, Dong Xu, Xing Wang, Jose Jessurun, Alain Borczuk, Yaoxing Huang, Jared L. Johnson, Yuru Liu, Jenny Xiang, Hui Wang, Lewis C. Cantley, Benjamin R. TenOever, David D. Ho, Fong Cheng Pan, Todd Evans, Huanhuan Joyce Chen, Robert E. Schwartz, Shuibing Chen
Summary: Researchers have developed lung and colonic organoid models using human pluripotent stem cells, which demonstrate susceptibility to SARS-CoV-2 infection. These models are valuable for studying the infection of the virus and screening drugs, with potential therapeutic implications for COVID-19.