Objectives
HIV is able to continuously adapt to and evade the evolving neutralizing antibody responses of the host. We investigated the ability of HIV variants to evade neutralizing antibodies in order to understand the distinct characteristics of HIV-1 Korean clade B. Methods
Three drug-naive subjects were enrolled in this study who were infected with HIV-1 Korean clade B. Neutralizations were performed using autologous plasma and pseudovirion-based assays in order to analyze and compare changes in the env gene. Results
In the early phase of infection, neutralizing activities against autologous virus variants gradually increased, which was followed by a decline in the humoral immune response against the subsequent viral escape variants. The amino acids lengths and number of potential N-linked glycosylation sites (PNGS) in HIV-1 env gene was positively correlated with neutralized antibody responses during the early stages of infection. Conclusion
This study suggests that change within the env domains over the course of infection influences reactivities to neutralized antibodies and may also have an impact on host immune responses. This is the first longitudinal study of HIV-1 humoral immunity that took place over the entire course of HIV-1 Korean clade B infection.
Citations
Citations to this article as recorded by
Blockage of CD59 Function Restores Activities of Neutralizing and Nonneutralizing Antibodies in Triggering Antibody-Dependent Complement-Mediated Lysis of HIV-1 Virions and Provirus-Activated Latently Infected Cells Kai Yang, Jie Lan, Nicole Shepherd, Ningjie Hu, Yanyan Xing, Daniel Byrd, Tohti Amet, Corlin Jewell, Samir Gupta, Carole Kounga, Jimin Gao, Qigui Yu, G. Silvestri Journal of Virology.2015; 89(18): 9393. CrossRef
Objectives
Many natural compounds have been investigated as drug candidates to prevent human immunodeficiency virus (HIV) with low cytotoxicity. We tested whether ingenol from Euphorbia ingens exerts anti-HIV effects in human T cell lines. Methods and Results
Ingenol effectively maintained high cell viability (CD50, >1 mM) in H9 and MT4 T cells. The efficacy of ingenol to inhibit HIV-1 infection was dose dependent. ED50 for 100 and 200 TCID50 of HIV-1 was 5.06 and 16.87 μM, respectively. Gag p24 antigen production in ingenol-treated MT4 cells was reduced by 24.5% on day 6 post-infection. While p24 antigen was reduced in ingenol-treated cells, levels of cytokines such as TNF-α and IL-6 and chemokines such as RANTES and MCP-1 were increased. dUTP level related to late apoptotic events was increased on day 2 post-infection of HIV by ingenol treatment, whereas expression of annexin V was unchanged. Reduced levels of iNOS and ZAP-70 after HIV infection were recovered by ingenol treatment. Conclusion
Ingenol helps T cells to survive longer against viremia after HIV-1 infection, without exerting cytotoxic effects. Ingenol can be considered a safe and efficacious candidate for immune-boosting therapy for AIDS patients.
Citations
Citations to this article as recorded by
A review of the ethnomedicinal, pharmacology, cytotoxicity and phytochemistry of the genus Euphorbia in southern Africa E.J. Mavundza, R. Street, H. Baijnath South African Journal of Botany.2022; 144: 403. CrossRef
South African plants with nematicidal activity against root-knot nematodes: A review F.N. Makhubu, M.C. Khosa, L.J. McGaw South African Journal of Botany.2021; 139: 183. CrossRef
Systematic characterization of metabolic profiles of ingenol in rats by UPLC-Q/TOF-MS and NMR in combination with microbial biotransformation Si-Jia Xiao, Shan-Shan Li, Bin Xie, Wei Chen, Xi-Ke Xu, Xian-Peng Zu, Yun-Heng Shen RSC Advances.2021; 11(60): 37752. CrossRef
Structure-Activity-Relationship and Mechanistic Insights for Anti-HIV Natural Products Ramandeep Kaur, Pooja Sharma, Girish K. Gupta, Fidele Ntie-Kang, Dinesh Kumar Molecules.2020; 25(9): 2070. CrossRef
Modified ingenol semi-synthetic derivatives from Euphorbia tirucalli induce cytotoxicity on a large panel of human cancer cell lines Viviane A. O Silva, Marcela N. Rosa, Olga Martinho, Amilcar Tanuri, João Paulo Lima, Luiz F. Pianowski, Rui M. Reis Investigational New Drugs.2019; 37(5): 1029. CrossRef
Natural product-derived compounds in HIV suppression, remission, and eradication strategies Raymond J. Andersen, Fidele Ntie-Kang, Ian Tietjen Antiviral Research.2018; 158: 63. CrossRef
Biphasic Effects of Ingenol 3,20-Dibenzoate on the Erythropoietin Receptor: Synergism at Low Doses and Antagonism at High Doses Jin-Gyo Oh, Young-Won Chin, Sung-Jo Kim, Jong Min Choi, Sang Kyum Kim, Hee Eun Kang, Tae-Hwe Heo Molecular Pharmacology.2015; 88(2): 392. CrossRef
LC-MS2-Based dereplication of Euphorbia extracts with anti-Chikungunya virus activity Louis-Félix Nothias-Scaglia, Vincent Dumontet, Johan Neyts, Fanny Roussi, Jean Costa, Pieter Leyssen, Marc Litaudon, Julien Paolini Fitoterapia.2015; 105: 202. CrossRef
Reactivation of latent HIV-1 by new semi-synthetic ingenol esters Diego Pandeló José, Koen Bartholomeeusen, Rodrigo Delvecchio da Cunha, Celina Monteiro Abreu, Jan Glinski, Thais Barbizan Ferreira da Costa, Ana Flávia Mello Bacchi Rabay, Luiz Francisco Pianowski Filho, Lech W. Dudycz, Udaykumar Ranga, Boris Matija Peter Virology.2014; 462-463: 328. CrossRef
Dual Role of Novel Ingenol Derivatives from Euphorbia tirucalli in HIV Replication: Inhibition of De Novo Infection and Activation of Viral LTR Celina M. Abreu, Sarah L. Price, Erin N. Shirk, Rodrigo D. Cunha, Luiz F. Pianowski, Janice E. Clements, Amilcar Tanuri, Lucio Gama, Cheryl A. Stoddart PLoS ONE.2014; 9(5): e97257. CrossRef