Article
Virology
Siva Thirugnanam, Edith M. Walker, Faith Schiro, Pyone P. Aye, Jay Rappaport, Namita Rout
Summary: Previous studies have shown that the loss of CD161-expressing CD4(+) Th17 cells is associated with the progression of chronic HIV infection. These cells are significantly reduced in the peripheral blood and gut mucosa of HIV-infected individuals, leading to inflammation and disruption of the gut barrier. However, the impact of HIV infection on CD161-expressing CD8(+) T cells is still unclear.
Article
Immunology
Brianna C. Davey, Mary S. Pampusch, Emily K. Cartwright, Hadia M. Abdelaal, Eva G. Rakasz, Aaron Rendahl, Edward A. Berger, Pamela J. Skinner
Summary: T cells expressing a SIV-specific chimeric antigen receptor (CAR) and CXCR5 were infused into SIV-infected rhesus macaques on antiretroviral therapy (ART) to assess their ability to control the virus. These cells showed evidence of functionality but failed to persist in the animals beyond 28 days, possibly due to the development of anti-CAR antibodies. The study suggests that the CD4 and CD28 domains of the CAR are immunogenic and could impact the long-term persistence of CAR immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Victoria E. K. Walker-Sperling, Noe B. Mercado, Abishek Chandrashekar, Erica N. Borducchi, Jinyan Liu, Joseph P. Nkolola, Mark Lewis, Jeffrey P. Murry, Yunling Yang, Romas Geleziunas, Merlin L. Robb, Nelson L. Michael, Maria G. Pau, Frank Wegmann, Hanneke Schuitemaker, Emily J. Fray, Mithra R. Kumar, Janet D. Siliciano, Robert F. Siliciano, Dan H. Barouch
Summary: This study suggests that combining active and passive immunization may have the potential in curing HIV-1. In SHIV-infected rhesus macaques, a combination of therapeutic vaccination and antibody administration with vesatolimod resulted in 70% post-ART virologic control.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Vijayakumar Velu, Kehmia Titanji, Hasan Ahmed, Ravi Dyavar Shetty, Lakshmi S. Chennareddi, Gordon J. Freeman, Rafi Ahmed, Rama Rao Amara
Summary: The study demonstrated that PD-1 blockade following ART interruption significantly enhances the function of anti-viral CD8 T cells and improves viral control. It suggests the potential synergistic effects of PD-1 blockade with other immunotherapies inducing functional CD8 T-cell responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Urmi Roy, Romulo S. de Oliveira, Eric J. C. Galvez, Achim Gronow, Marijana Basic, Laura Garcia Perez, Nicola Gagliani, Andre Bleich, Samuel Huber, Till Strowig
Summary: The study reveals that segmented filamentous bacteria (SFB) not only induce Th17 cells but also distinct IL-17A negative CD4+ T cell populations in the intestine, some of which produce IL-22 upon restimulation and during enteric infections. These cells, presumably Th22 cells, develop independently of intestinal Th17 cells and produce a different set of cytokines compared to Th17 cells. This suggests that aside from Th17, SFB can also induce CD4+ T cell populations that serve as an immediate source of IL-22 during intestinal inflammation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Guangjie Liu, Li Qin, Youjia Li, Siting Zhao, Mikhail Shugay, Yongxiang Yan, Yijian Ye, Yue Chen, Cuizhu Huang, Nashun Bayaer, Dickson Adah, Hui Zhang, Zhong Su, Xiaoping Chen
Summary: This study found that pre-existing malaria can increase viral loads of SIV, while subsequent malaria can improve the survival rate of SIV-infected animals. These findings have important implications for research on human HIV and malaria coinfection.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Virology
Maud Mavigner, Laura E. Liao, Alyssa D. Brooks, Ruian Ke, Cameron Mattingly, Nils Schoof, Julia McBrien, Diane Carnathan, Shan Liang, Thomas H. Vanderford, Mirko Paiardini, Deanna Kulpa, Jeffrey D. Lifson, Richard M. Dunham, Kirk A. Easley, David M. Margolis, Alan S. Perelson, Guido Silvestri, Ann Chahroudi
Summary: The study demonstrated that inducing latency reversal using the SMAC mimetic/IAP inhibitor AZD5582, in combination with CD8 alpha cell depletion, can enhance viral latency reversal in SIV-infected rhesus macaques. All six animals treated with the combined therapy showed increased on-ART viremia, indicating a potential role of CD8(+) T cells in maintaining and inhibiting latency reversal during HIV/SIV infection.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Nichole R. Klatt, Courtney Broedlow, Jessica M. Osborn, Andrew T. Gustin, Sandra Dross, Megan A. O'Connor, Ernesto Coronado, Philip Barnette, Tiffany Hensley-McBain, Alexander S. Zevin, Roshell Muir, Alexander Roederer, Solomon Wangari, Naoto Iwayama, Chul Y. Ahrens, Jeremy Smedley, Cassandra Moats, Rebecca M. Lynch, Elias K. Haddad, Nancy L. Haigwood, Deborah H. Fuller, Jennifer A. Manuzak
Summary: Although probiotics were well-tolerated when administered with SIV/HIV vaccination, vaccine-specific responses were not significantly enhanced. Additional work will be necessary to develop more effective strategies of microbiome modulation in order to enhance mucosal vaccine immunogenicity and improve protective immune responses.
Article
Microbiology
Ling Tong, Zhe Cong, Long Tian, Jingjing Zhang, Jiahan Lu, Qiuhan Lu, Ting Chen, Yuhong Wang, Qiang Wei, Jing Xue
Summary: This study used rhesus monkeys to simulate different stages of HIV infection and found shifts in SIV-specific immunity at different levels of viral replication. By comparing immune responses at different stages, it revealed the dynamic changes in individual immune competence.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xue-Hui Wang, Tian-Zhang Song, Hong-Yi Zheng, Yi-Hui Li, Yong-Tang Zheng
Summary: The destruction of intestinal epithelial barrier appears earlier than mucosal immune dysfunction in early stages of HIV and SIV infections, primarily due to oxidative stress-induced DNA damage and apoptosis. Mitochondrial dysfunction and oxidative stress are identified as key contributors to gut epithelial barrier disruption in early SIV-infected rhesus macaques.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Immunology
Nuria Pedreno-Lopez, Brandon C. Rosen, Walter J. Flores, Matthew J. Gorman, Thomas B. Voigt, Michael J. Ricciardi, Kristin Crosno, Kim L. Weisgrau, Christopher L. Parks, Jeffrey D. Lifson, Galit Alter, Eva G. Rakasz, Diogo M. Magnani, Mauricio A. Martins, David I. Watkins
Summary: The study suggests that non-neutralizing antibodies may contribute to the suppression of SIVmac239 viremia in Indian rhesus macaques, even in the absence of neutralizing activity prior to infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Yizi He, Chunxiu Wu, Zijian Liu, Yudi Zhang, Fengling Feng, Zihan Lin, Congcong Wang, Qing Yang, Ziyu Wen, Yichu Liu, Fan Zhang, Yanqin Lin, Hao Zhang, Linbing Qu, Linghua Li, Weiping Cai, Caijun Sun, Ling Chen, Pingchao Li
Summary: Arsenic trioxide (As2O3) can reactivate the viral reservoir, delay viral rebound after antiretroviral therapy (ART) interruption, and induce apoptosis of SIV-infected CD4(+) T cells, thus blocking the secondary infection of bystanders.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Yizi He, Chunxiu Wu, Zijian Liu, Yudi Zhang, Fengling Feng, Zihan Lin, Congcong Wang, Qing Yang, Ziyu Wen, Yichu Liu, Fan Zhang, Yanqin Lin, Hao Zhang, Linbing Qu, Linghua Li, Weiping Cai, Caijun Sun, Ling Chen, Pingchao Li
Summary: This study demonstrates the potential of arsenic trioxide (As2O3) as a component of the shock-and-kill strategy for achieving a functional cure for HIV. As2O3 not only impacts viral latency and reactivates the viral reservoir, but also induces apoptosis of HIV-infected cells, preventing secondary infection. Additionally, the combination of As2O3 and antiretroviral therapy (ART) effectively restores CD4(+) T cell count, delays disease progression, and improves survival in acutely SIV-infected macaques.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Roslyn A. Taylor, Michael D. McRaven, Ann M. Carias, Meegan R. Anderson, Edgar Matias, Mariluz Arainga, Edward J. Allen, Kenneth A. Rogers, Sandeep Gupta, Viraj Kulkarni, Samir Lakhashe, Ramon Lorenzo-Redondo, Yanique Thomas, Amanda Strickland, Francois J. Villinger, Ruth M. Ruprecht, Thomas J. Hope
Summary: The study showed that HIV rapidly spread and penetrated the entire gastrointestinal tract in neonatal rhesus macaques as early as four hours after oral viral challenge, with the largest number of infected cells found in the small and large intestine at 96 hours, predominantly T cells. These findings highlight the importance of understanding viral distribution and infection dynamics in neonates.
Article
Virology
Xinjie Li, Liyan Zhu, Yue Yin, Xueying Fan, Linting Lv, Yuqi Zhang, Yijin Pan, Yangxuanyu Yan, Hua Liang, Jing Xue, Tao Shen
Summary: This study investigates the impact of NK cells on the viral levels of SIV-infected macaques and finds a significant positive correlation between the frequency of NK cells and the ratios of cellular SIV DNA/RNA. However, the limited abundance of NK cells in lymph nodes restricts their cytotoxicity effect on the latent SIV viral load.
Article
Immunology
Violeta J. Rodriguez, John M. Abbamonte, Manasi S. Parrish, Deborah L. Jones, Stephen Weiss, Suresh Pallikkuth, Michal Toborek, Maria L. Alcaide, Dushyantha Jayaweera, Savita Pahwa, Tatjana Rundek, Barry E. Hurwitz, Mahendra Kumar
Summary: The study found that in young to middle-age adults, cocaine use was associated with greater relative cardiovascular risk scores, but biomarkers were not associated with cardiovascular risk. Age and cardiovascular risk scores were related to carotid atherosclerotic plaque, while HIV status did not show any associations with cardiovascular risk scores or carotid atherosclerotic plaque.
INTERNATIONAL JOURNAL OF STD & AIDS
(2022)
Article
Immunology
Daniela Frasca, Suresh Pallikkuth, Savita Pahwa
Summary: Metabolic changes are common signs of aging and can increase the risk of developing age-related diseases. The impact of aging on the metabolic phenotype of immune cells, particularly B cells, is not well understood. However, preliminary research suggests that targeting metabolic pathways could be a potential novel therapeutic approach to reduce inflammaging and enhance humoral immunity.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Article
Immunology
Suresh Pallikkuth, Savita Pahwa
Summary: Our understanding of HIV/AIDS has undergone a transformation due to the use of novel antiretroviral therapy, allowing clinicians and patients to control the progression of the disease. This supplement presents an overview of the virtual symposium on HIV and Aging in the Era of ART and COVID-19, held on February 8-9, 2021, organized by the Miami Center for AIDS Research, including articles contributed by speakers and members of the organizing committee, as well as presentations by junior investigators.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Article
Immunology
Stefano Rinaldi, Suresh Pallikkuth, Lesley De Armas, Brian Richardson, Li Pan, Rajendra Pahwa, Sion Williams, Mark Cameron, Savita Pahwa
Summary: This study aimed to identify molecular signatures of aging in HIV-infected individuals compared with age-matched healthy control participants. The researchers found that metabolic and innate immune activation pathways were associated with increasing age in both HIV and healthy control groups. Additionally, age was associated with pathways involved with T-cell immune activation in healthy controls and with interferon signaling pathways in HIV-infected individuals.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Editorial Material
Immunology
Monty Montano, Alan Landay, Molly Perkins, Marcia Holstad, Suresh Pallikkuth, Savita Pahwa
Summary: Antiretroviral therapy has changed the clinical environment of HIV, resulting in similar common morbidities and causes of death between HIV-infected and noninfected individuals. However, these conditions manifest earlier in people living with HIV, and the emergence of SARSCoV-2 infection has further complicated the accelerated aging process in HIV.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Article
Immunology
Bagavathi Kausalya, Shanmugam Saravanan, Suresh Pallikkuth, Rajendra Pahwa, Shelly Rani Saini, Syed Iqbal, Sunil Solomon, Kailapuri G. Murugavel, Selvamuthu Poongulali, Nagalingeswaran Kumarasamy, Savita Pahwa
Summary: This study investigated the effects of systemic inflammation, microbial translocation, T cell immune activation, and nadir CD4 counts on cardiac function and arterial stiffness in HIV-infected individuals. The authors found that initiation of antiretroviral therapy (ART) even at low CD4 counts may improve cardiac function and reduce arterial stiffness, and decrease inflammation and microbial translocation. Participants who were not receiving ART were most affected, while those on ART had similar measures to uninfected individuals, even with low CD4 counts.
Article
Multidisciplinary Sciences
Alexandra M. Ortiz, Jennifer Simpson, Charlotte A. Langner, Phillip J. Baker, Cynthia Aguilar, Kelsie Brooks, Jacob K. Flynn, Carol L. Vinton, Andrew R. Rahmberg, Heather D. Hickman, Jason M. Brenchley
Summary: Supplementation with sodium butyrate did not significantly improve immune reconstitution or reduce inflammation in ARV-treated, SIV-infected rhesus macaques, suggesting that this therapeutic approach may not be effective in reducing comorbidities and mortalities in treated individuals living with HIV.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Christine E. Nelson, Sivaranjani Namasivayam, Taylor W. Foreman, Keith D. Kauffman, Shunsuke Sakai, Danielle E. Dorosky, Nickiana E. Lora, Kelsie Brooks, E. Lake Potter, Nicole L. Garza, Bernard A. P. Lafont, Reed F. Johnson, Mario Roederer, Alan Sher, Daniela Weiskopf, Alessandro Sette, Emmie de Wit, Heather D. Hickman, Jason M. Brenchley, Laura E. Via, Daniel L. Barber
Summary: This study used rhesus macaques to model mild COVID-19 and found that SARS-CoV-2 replication decreases in the lungs, nasal, and oral mucosa before antigen-specific effector T cells arrive, suggesting that innate immunity efficiently restricts viral replication during mild COVID-19.
SCIENCE IMMUNOLOGY
(2022)
Article
Immunology
Erin Williams, Jordan Colson, Ranjini Valiathan, Juan Manuel Carreno, Florian Krammer, Michael Hoffer, Suresh Pallikkuth, Savita Pahwa, David Andrews
Summary: The study found that high binding antibody titers and neutralizing activity are not markers of protection against Omicron infection/re-infection.
Article
Health Policy & Services
Maria Grazia Lain, Sergio Chicumbe, Anna Cantarutti, Gloria Porcu, Loide Cardoso, Nicola Cotugno, Paolo Palma, Rajendra Pahwa, Suresh Pallikkuth, Stefano Rinaldi, Paula Vaz, Savita Pahwa
Summary: Psychosocial support (PSS) for caregivers of HIV-infected infants is crucial for ART adherence and long-term viral suppression. This study in Mozambique found that the standard PSS approach alone was insufficient in identifying barriers to adherence, highlighting the need for a comprehensive, patient-centered PSS package of care tailored to caregivers and their children.
AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
(2023)
Review
Microbiology
Rashmi Kumari, Suresh D. Sharma, Amrita Kumar, Zachary Ende, Margarita Mishina, Yuanyuan Wang, Zackary Falls, Ram Samudrala, Jan Pohl, Paul R. Knight, Suryaprakash Sambhara
Summary: Preventing and controlling influenza virus infection is a global public health challenge due to its impact on epidemics and pandemics, high morbidity and mortality rates, and significant economic consequences. Vaccines are the main prophylaxis, but their effectiveness is limited. Antiviral drugs play a crucial role in reducing influenza-related morbidity and mortality, especially in high-risk populations. This review discusses FDA-approved influenza antivirals, their mechanisms of action, and different approaches, including immunomodulatory interventions and the potential use of machine learning in developing next-generation antivirals against influenza.
CLINICAL MICROBIOLOGY REVIEWS
(2023)
Article
Infectious Diseases
Catherine K. Koofhethile, Stefano Rinaldi, Yelizaveta Rassadkina, Vinh B. Dinh, Ce Gao, Suresh Pallikkuth, Pilar Garcia-Broncano, Lesley R. de Armas, Rajendra Pahwa, Nicola Cotugno, Paula Vaz, Maria Grazia Lain, Paolo Palma, Xu G. Yu, Roger Shapiro, Savita Pahwa, Mathias Lichterfeld
Summary: This study longitudinally analyzed the proviral landscape in infants with HIV-1 infection and found that early initiation of antiretroviral therapy led to a rapid decline in intact proviruses. The results also suggest that the vulnerability of intact proviruses to antiviral immunity may contribute to their disproportionate under-representation.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Erin C. Williams, Alexander Kizhner, Valerie S. Stark, Aria Nawab, Daniel D. Muniz, Felipe Echeverri Tribin, Juan Manuel Carreno, Dominika Bielak, Gagandeep Singh, Michael E. Hoffer, Florian Krammer, Suresh Pallikkuth, Savita Pahwa
Summary: This study used LASSO and linear mixed effects models to evaluate the influence of pre-existing immunity, demographic factors, and vaccine reactogenicity on antibody responses to COVID vaccination. The results showed that previously infected individuals had more durable and robust antibodies after vaccination compared to natural infection alone. Experiencing symptoms during natural infection and post-vaccine were predictive of higher antibody levels. The findings suggest that vaccination in COVID+ individuals can lead to a more robust immune response.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Health Care Sciences & Services
Maria Grazia Lain, Paula Vaz, Marco Sanna, Nalia Ismael, Sergio Chicumbe, Teresa Beatriz Simione, Anna Cantarutti, Gloria Porcu, Stefano Rinaldi, Lesley de Armas, Vinh Dinh, Suresh Pallikkuth, Rajendra Pahwa, Paolo Palma, Nicola Cotugno, Savita Pahwa
Summary: This study described the viral response over a two-year follow-up period for 39 perinatally HIV-infected infants in Mozambique who initiated treatment at one month of age. The findings showed a low rate of viral load suppression and a high rate of viral rebound. More frequent monitoring of viral response and timely adherence support for infants experiencing rebound are recommended. Tailored psychosocial support and differentiated service delivery should be provided for mother-baby pairs.
Article
Immunology
Alessandra Ruggiero, Giuseppe Rubens Pascucci, Nicola Cotugno, Sara Dominguez-Rodriguez, Stefano Rinaldi, Alfredo Tagarro, Pablo Rojo, Caroline Foster, Alasdair Bamford, Anita De Rossi, Eleni Nastouli, Nigel Klein, Elena Morrocchi, Benoit Fatou, Kinga K. Smolen, Al Ozonoff, Michela Di Pastena, Katherine Luzuriaga, Hanno Steen, Carlo Giaquinto, Philip Goulder, Paolo Rossi, Ofer Levy, Savita Pahwa, Paolo Palma
Summary: Children with perinatally acquired HIV (PHIV) exhibit signs of B-cell hyperactivation despite successful antiretroviral therapy (ART), which may result in reduced cell functionality and loss of vaccine-induced immunity. This hyperactivation is associated with proteins involved in immune inflammation and complement activation pathways.
FRONTIERS IN IMMUNOLOGY
(2022)