Article
Immunology
Lesley R. de Armas, Christina Gavegnano, Suresh Pallikkuth, Stefano Rinaldi, Li Pan, Emilie Battivelli, Eric Verdin, Ramzi T. Younis, Rajendra Pahwa, Sion L. Williams, Raymond F. Schinazi, Savita Pahwa
Summary: The study used the dual reporter virus HIVGKO to investigate latency establishment and maintenance in CD4(+) T cells, and analyzed latently infected cells using single cell technologies. The research found that JAK1/2 inhibitors could reduce HIV infection events and block HIV reactivation from latent cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Shilpa Sonti, Kratika Tyagi, Amit Pande, Rene Daniel, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Summary: Drug abuse in HIV-infected individuals often leads to neurocognitive issues and CNS dysfunction. Current research focuses on understanding the shared mechanisms between drug abuse and HIV that cause neurotoxicity, which is crucial for developing effective treatment strategies.
Article
Multidisciplinary Sciences
Dajiang Li, Lilly M. Wong, Yuyang Tang, Brigitte Allard, Katherine S. James, George R. Thompson, Satya Dandekar, Edward P. Browne, Qingsheng Li, Jeremy M. Simon, Nancie M. Archin, David M. Margolis, Guochun Jiang
Summary: Activation of ISR/ATF4 signaling can reverse HIV latency and selectively eliminate HIV-positive CD4(+) T cells without affecting HIV-negative CD4(+) T cells.
Article
Microbiology
Thomas A. Packard, Roland Schwarzer, Eytan Herzig, Deepashri Rao, Xiaoyu Luo, Johanne H. Egedal, Feng Hsiao, Marek Widera, Judd F. Hultquist, Zachary W. Grimmett, Ronald J. Messer, Nevan J. Krogan, Steven G. Deeks, Nadia R. Roan, Ulf Dittmer, Kim J. Hasenkrug, Warner C. Greene
Summary: HIV infection triggers innate inflammatory response and release of CCL2 chemokine, leading to recruitment of CCR2/5(+) central memory CD4 T cells and rapid formation of latent HIV reservoir.
Review
Microbiology
Nnamdi Ikeogu, Oluwaseun Ajibola, Romaniya Zayats, Thomas T. Murooka
Summary: This review discusses the role of memory T cells in HIV infection and how HIV hijacks normal immune processes to establish long-term infection.
Article
Immunology
Marta Sanz, Ann Marie K. Weideman, Adam R. Ward, Matthew L. Clohosey, Susana Garcia-Recio, Sara R. Selitsky, Brendan T. Mann, Marie Anne Iannone, Chloe P. Whitworth, Alisha Chitrakar, Carolina Garrido, Jennifer Kirchherr, Alisha R. Coffey, Yi- Hsuan Tsai, Shahryar Samir, Yinyan Xu, Dennis Copertino, Alberto Bosque, Brad R. Jones, Joel S. Parker, Michael G. Hudgens, Nilu Goonetilleke, Natalia Soriano-Sarabia
Summary: Antiretroviral therapy (ART) cannot cure HIV-1 infection due to latent reservoirs of the virus. Current research focuses on using small molecules or latency-reversing agents (LRAs) to disrupt latency and enable immune cells to eliminate infected cells. This study investigates the use of aminobisphosphonates (N-BPs) as a novel class of LRAs and finds that they can reactivate HIV-1 from latency and induce immune effector functions. Further investigation is needed to explore the potential of N-BPs in combination with therapeutic vaccination.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Jarrod York, Kavitha Gowrishankar, Kenneth Micklethwaite, Sarah Palmer, Anthony L. Cunningham, Najla Nasr
Summary: Despite the effectiveness of ART in reducing morbidity and mortality associated with HIV infection, the latent HIV reservoir remains a major barrier to immune clearance and HIV cure. CAR T cell therapies, involving genetically engineered T cells, offer promising potential in targeting HIV-infected cells and have shown efficacy, safety, and long-term persistence in peripheral blood.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Cynthia Lungu, Riddhima Banga, Rob A. Gruters, Francesco A. Procopio
Summary: The stable HIV-1 reservoir poses a challenge for achieving a cure. There is a need for a sensitive, reproducible, cost-effective, and easily executable test for quantifying the viral reservoir. TILDA, as an alternative method, shows potential in quantifying the viral reservoir.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Michal Schwartz, Noam Stern-Ginossar
Summary: Human cytomegalovirus (HCMV) is a widely spread herpesvirus that infects the majority of humans and establishes lifelong latency. The mechanisms of HCMV latency and maintenance in dividing cells are still not fully understood. This article discusses the known latency reservoir in hematopoietic cells in the bone marrow, the gaps in our knowledge regarding HCMV genome maintenance, and the tissue origins of HCMV reactivation that have been suggested by clinical evidence.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Review
Pathology
Janet D. Siliciano, Robert F. Siliciano
Summary: This article discusses the latest developments in understanding the composition and measurement of the HIV reservoir, as well as the dynamics and stability of the reservoir. It also explores strategies to cure HIV infection.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2022)
Review
Microbiology
Divyadarshini Angamuthu, Sandhya Vivekanandan, Luke Elizabeth Hanna
Summary: The establishment, maintenance, and reversal of HIV latency in the latent reservoirs remain poorly understood and require further investigation. Currently, there are limited in vitro and in vivo models available for studying HIV latency, and the detection and quantification of these latent viral reservoirs pose a challenge. This article provides a comprehensive review of the existing models and molecular tools for studying and measuring latent HIV reservoirs.
CLINICAL MICROBIOLOGY REVIEWS
(2023)
Article
Virology
Indra Sarabia, Szu-Han Huang, Adam R. Ward, R. Brad Jones, Alberto Bosque
Summary: The establishment of HIV-1 latency has posed challenges for curing HIV-1. Current strategies to shock and kill the virus reservoir are not effective in inducing the majority of intact HIV-1 proviruses. The mechanisms behind the non-inducible HIV-1 reservoir still need further investigation.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Roux-Cil Ferreira, Jessica L. Prodger, Andrew D. Redd, Art F. Y. Poon
Summary: The long-term persistence of a population of cells carrying transcriptionally silent integrated viral DNA remains the primary barrier to developing an effective cure for people living with HIV-1. The contribution of ongoing cell division via proliferation to the latent HIV-1 reservoir is supported by the observation that proviral sequences sampled from the reservoir are often identical. However, clonality is not adequate for characterizing the dynamics and proviral composition of the reservoir due to the complexity of how infected cells are 'labeled' by proviral sequences and variation in cell birth and death rates among lineages and over time.
Article
Chemistry, Medicinal
Chenliang Zhou, Ting Li, Muye Xia, Ziyao Wu, Xuelin Zhong, Axing Li, Huba Khamis Rashid, Chengnuo Ma, Ruijing Zhou, Heng Duan, Xuanxuan Zhang, Jie Peng, Lin Li
Summary: In this study, we demonstrate that the pan-Bcl-2 antagonist obatoclax can induce HIV-1 reactivation in vitro and ex vivo, promoting transcriptional initiation and elongation through the NF-kappa B pathway. It preferentially induces apoptosis in latently infected cells, making it a promising candidate for the development of an ideal latency-reversing agent (LRA) in the shock and kill approach.
ACS INFECTIOUS DISEASES
(2023)
Article
Immunology
Thomas A. Rasmussen, Lakshmi Rajdev, Ajantha Rhodes, Ashanti Dantanarayana, Surekha Tennakoon, Socheata Chea, Tim Spelman, Shelly Lensing, Rachel Rutishauser, Sonia Bakkour, Michael Busch, Janet D. Siliciano, Robert F. Siliciano, Mark H. Einstein, Dirk P. Dittmer, Elizabeth Chiao, Steven G. Deeks, Christine Durand, Sharon R. Lewin
Summary: The study tested the combination of anti-PD-1 and anti-CTLA-4 therapy in HIV-infected individuals with cancer, finding that the combination therapy increased HIV RNA levels and potentially eliminated cells containing replication-competent HIV.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Frauke Muecksch, Zijun Wang, Alice Cho, Christian Gaebler, Tarek Ben Tanfous, Justin DaSilva, Eva Bednarski, Victor Ramos, Shuai Zong, Brianna Johnson, Raphael Raspe, Dennis Schaefer-Babajew, Irina Shimeliovich, Mridushi Daga, Kai-Hui Yao, Fabian Schmidt, Katrina G. Millard, Martina Turroja, Mila Jankovic, Thiago Y. Oliveira, Anna Gazumyan, Marina Caskey, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig
Summary: Receiving three doses of an mRNA vaccine can provide protection against the Omicron variant and induce the production of more potent and broader antibodies. This is due to the expansion and evolution of memory B cell clones, particularly the newly emerging clones that target more conserved regions.
Article
Immunology
Alice Cho, Frauke Muecksch, Zijun Wang, Tarek Ben Tanfous, Justin DaSilva, Raphael Raspe, Brianna Johnson, Eva Bednarski, Victor Ramos, Dennis Schaefer-Babajew, Irina Shimeliovich, Juan P. Dizon, Kai-Hui Yao, Fabian Schmidt, Katrina G. Millard, Martina Turroja, Mila Jankovic, Thiago Y. Oliveira, Anna Gazumyan, Christian Gaebler, Marina Caskey, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig
Summary: The article discusses the antibody immune response to the Ad26.COV2.S vaccine and mRNA vaccines after a single dose. It highlights that Ad26.COV2.S vaccination induces fewer memory B cells compared to mRNA vaccines, but the potency and breadth of the immune response are comparable. The Ad26.COV2.S vaccine also shows lower levels of neutralizing antibodies and limited efficacy against infection, especially during the Omicron surge.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Marianna Agudelo, Frauke Muecksch, Dennis Schaefer-Babajew, Alice Cho, Justin DaSilva, Eva Bednarski, Victor Ramos, Thiago Y. Oliveira, Melissa Cipolla, Anna Gazumyan, Shuai Zong, Danielle A. S. Rodrigues, Guilherme S. Lira, Luciana Conde, Renato Santana Aguiar, Orlando C. C. Ferreira Jr, Amilcar Tanuri, Katia C. Affonso, Rafael M. Galliez, Terezinha Marta Pereira Pinto Castineiras, Juliana Echevarria-Lima, Marcelo Torres Bozza, Andre M. Vale, Paul D. Bieniasz, Theodora Hatziioannou, Michel C. Nussenzweig
Summary: This paper describes the plasma and memory antibody response in a cohort of SARS-CoV-2 Gamma-infected individuals in Brazil. The results show that potent antibody neutralization is limited to Gamma and Beta variants, with lower neutralizing activity against other variants. Additionally, antibodies elicited by Gamma infection tend to recognize Class 3 epitopes more.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Zijun Wang, Pengcheng Zhou, Frauke Muecksch, Alice Cho, Tarek Ben Tanfous, Marie Canis, Leander Witte, Brianna Johnson, Raphael Raspe, Fabian Schmidt, Eva Bednarski, Justin Da Silva, Victor Ramos, Shuai Zong, Martina Turroja, Katrina G. Millard, Kai-Hui Yao, Irina Shimeliovich, Juan Dizon, Anna Kaczynska, Mila Jankovic, Anna Gazumyan, Thiago Y. Oliveira, Marina Caskey, Christian Gaebler, Paul D. Bieniasz, Theodora Hatziioannou, Michel C. Nussenzweig
Summary: Wang et al. analyze memory B cell and antibody responses in SARS-CoV-2 mRNA vaccines to breakthrough infections with Delta or Omicron BA.1 variants. They found that a third exposure to Delta increases strain-specific memory responses and overall potency and breadth of memory B cells, while a fourth exposure to Omicron BA.1 only increases strain-specific memory responses.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Zijun Wang, Frauke Muecksch, Friederike Muenn, Alice Cho, Shuai Zong, Raphael Raspe, Victor Ramos, Brianna Johnson, Tarek Ben Tanfous, Justin DaSilva, Eva Bednarski, Camila Guzman-Cardozo, Martina Turroja, Katrina G. Millard, Pinkus Tober-Lau, David Hillus, Kai-Hui Yao, Irina Shimeliovich, Juan Dizon, Anna Kaczynska, Mila Jankovic, Anna Gazumyan, Thiago Y. Oliveira, Marina Caskey, Paul D. Bieniasz, Theodora Hatziioannou, Florian Kurth, Leif Erik Sander, Michel C. Nussenzweig, Christian Gaebler
Summary: The study compares antibody immune responses following different COVID-19 vaccination regimens, revealing significant differences that can inform improved vaccination strategies. The findings highlight the importance of vaccine selection in antibody production and protection.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Eva M. Stevenson, Sandra Terry, Dennis Copertino, Louise Leyre, Ali Danesh, Jared Weiler, Adam R. Ward, Pragya Khadka, Evan McNeil, Kevin Bernard, Itzayana G. Miller, Grant B. Ellsworth, Carrie D. Johnston, Eli J. Finkelsztein, Paul Zumbo, Doron Betel, Friederike Dundar, Maggie C. Duncan, Hope R. Lapointe, Sarah Speckmaier, Nadia Moran-Garcia, Michelle Premazzi Papa, Samuel Nicholes, Carissa J. Stover, Rebecca M. Lynch, Marina Caskey, Christian Gaebler, Tae-Wook Chun, Alberto Bosque, Timothy J. Wilkin, Guinevere Q. Lee, Zabrina L. Brumme, R. Brad Jones
Summary: In a cohort of people with HIV, COVID mRNA vaccination leads to a temporary increase in a specific profile of HIV-specific T-cell responses and a corresponding decrease in residual HIV RNA, indicating productive immune engagement with infected cells.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Georg H. J. Weymar, Yotam Bar -On, Thiago Y. Oliveira, Christian Gaebler, Victor Ramos, Harald Hartweger, Gaelle Breton, Marina Caskey, Lillian B. Cohn, Mila Jankovic, Michel C. Nussenzweig
Summary: The study discovered that clones of latent cells carrying dormant HIV-1 viruses mainly exist in a specific subgroup of CD4(+) T cells, which are predominantly T effector memory cells with distinctive gene expression. This finding opens up new possibilities for eradicating HIV-1.
Article
Multidisciplinary Sciences
Dennis Schaefer-Babajew, Zijun Wang, Frauke Muecksch, Alice Cho, Maximilian Loewe, Melissa Cipolla, Raphael Raspe, Brianna Johnson, Marie Canis, Justin DaSilva, Victor Ramos, Martina Turroja, Katrina G. Millard, Fabian Schmidt, Leander Witte, Juan Dizon, Irina Shimeliovich, Kai-Hui Yao, Thiago Y. Oliveira, Anna Gazumyan, Christian Gaebler, Paul D. Bieniasz, Theodora Hatziioannou, Marina Caskey, Michel C. Nussenzweig
Summary: Feedback inhibition of humoral immunity by antibodies can enhance or inhibit immune responses. However, the influence of pre-existing antibodies on the development of memory B cells is not well understood. By studying individuals who received high-affinity anti-SARS-CoV-2 monoclonal antibodies and mRNA vaccine, it was found that the memory B cells of these individuals had altered characteristics, including expressing low-affinity IgM antibodies and showing epitope masking. This finding may help explain the changes in target profile of memory antibodies after booster vaccinations. Rating: 8.5/10
Article
Multidisciplinary Sciences
Leander Witte, Viren A. Baharani, Fabian Schmidt, Zijun Wang, Alice Cho, Raphael Raspe, Camila Guzman-Cardozo, Frauke Muecksch, Marie Canis, Debby J. Park, Christian Gaebler, Marina Caskey, Michel C. Nussenzweig, Theodora Hatziioannou, Paul D. Bieniasz
Summary: The emergence of SARS-CoV-2 variants with neutralizing antibody resistance mutations has led to waves of infection. However, repeated exposure to antigens has also resulted in the production of broadly neutralizing antibodies against these variants. Through their study, Witte et al found that specific substitutions in the spike protein of SARS-CoV-2 enable the acquisition of resistance to broadly neutralizing antibodies. These findings highlight the importance of understanding the interactions between new and old substitutions in the development of antibody escape.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Harry B. Gristick, Harald Hartweger, Maximilian Loewe, Jelle van Schooten, Victor Ramos, Thiago Y. Oliveira, Yoshiaki Nishimura, Nicholas S. Koranda, Abigail Wall, Kai -Hui Yao, Daniel Poston, Anna Gazumyan, Marie Wiatr, Marcel Horning, Jennifer R. Keeffe, Magnus A. G. Hoffmann, Zhi Yang, Morgan E. Abernathy, Kim-Marie A. Dam, Han Gao, Priyanthi N. P. Gnanapragasam, Leesa M. Kakutani, Ana Jimena Pavlovitch-Bedzyk, Michael S. Seaman, Mark Howarth, Andrew T. Mcguire, Leonidas Stamatatos, Malcolm A. Martin, Anthony P. West Jr, Michel C. Nussenzweig, Pamela J. Bjorkman
Summary: Passive transfer of broadly neutralizing anti-HIV-1 antibodies is a strategy to protect against infection, but eliciting these antibodies through vaccination has been challenging. Researchers have successfully induced CD4 binding site (CD4bs) antibody responses using the antibody IOMA, which has potential as a vaccine strategy to generate broadly neutralizing antibodies against HIV-1.
SCIENCE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Daniel B. Reeves, Christian Gaebler, Thiago Y. Oliveira, Michael J. Peluso, Joshua T. Schiffer, Lillian B. Cohn, Steven G. Deeks, Michel C. Nussenzweig
Summary: Most proviruses in people living with HIV are defective, but intact proviruses can lead to viral rebound. The two-probe intact proviral DNA assay (IPDA) found 40-fold more intact proviruses compared to the near full length (nfl) Q4PCR. Both assays showed that defective proviruses did not decay over 10 years. However, the average half-lives of intact proviruses were different: 108 months for IPDA and 65 months for Q4PCR. Misclassified defective proviruses and very long-lived intact proviruses could explain this difference.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Mohamed A. Eltanbouly, Victor Ramos, Andrew J. Maclean, Spencer T. Chen, Maximilian Loewe, Sandra Steinbach, Tarek Ben Tanfous, Brianna Johnson, Melissa Cipolla, Anna Gazumyan, Thiago Y. Oliveira, Michel C. Nussenzweig
Summary: We demonstrate in a study using multiple clones that the differentiation of GC B cells into plasma cells depends on affinity, leading to the production of serum responses with high affinity. The study compares GC cells primed for PC differentiation with GC B cells specifically chosen for further affinity maturation. Protective immune responses against various pathogens rely on the development of high-affinity antibody-secreting plasma cells (PCs) in germinal centers (GCs). Transgenic models indicate that there is a strict affinity-based barrier to PC development. However, it is unclear if a similar high-affinity barrier exists in physiological circumstances and the precise nature of the PC fate decision. In this study, we utilize a fate-mapping approach to investigate the relationship between GC B cells selected for additional rounds of affinity maturation, GC pre-PCs, and PCs. The results show that initial PC selection overlaps with GC B cell selection, but the PC compartment accumulates a less diverse collection of higher affinity antibodies over time. Thus, while the GC continues to diversify, affinity-based pre-PC selection filters the GC to allow for the accumulation of a more restricted group of high-affinity antibody-secreting PCs.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)