45 results on '"Sarkis, Sarkis"'
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2. Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques
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Rahman, Mohammad Arif, Bissa, Massimiliano, Silva de Castro, Isabela, Helmold Hait, Sabrina, Stamos, James D., Bhuyan, Farzana, Hunegnaw, Ruth, Sarkis, Sarkis, Gutowska, Anna, Doster, Melvin N., Moles, Ramona, Hoang, Tanya, Miller Jenkins, Lisa M., Appella, Ettore, Venzon, David J., Choo-Wosoba, Hyoyoung, Cardozo, Timothy, Baum, Marc M., Appella, Daniel H., Robert-Guroff, Marjorie, and Franchini, Genoveffa
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- 2023
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3. HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC
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Massimiliano Bissa, Sohyoung Kim, Veronica Galli, Slim Fourati, Sarkis Sarkis, Anush Arakelyan, Isabela Silva de Castro, Mohammad Arif Rahman, Saori Fujiwara, Monica Vaccari, Jeffrey A. Tomalka, James D. Stamos, Luca Schifanella, Giacomo Gorini, Ramona Moles, Anna Gutowska, Guido Ferrari, Alexei Lobanov, David C. Montefiori, George W. Nelson, Margaret C. Cam, Marita Chakhtoura, Elias K. Haddad, Melvin N. Doster, Katherine McKinnon, Sophia Brown, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Kristin E. Killoran, Joshua Kramer, Leonid Margolis, Rafick P. Sekaly, Gordon L. Hager, and Genoveffa Franchini
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Science - Abstract
HIV vaccine development can be aided by knowledge of correlates of protection. Here the authors identify engagement and reprogramming of tolerogenic CD14+ myeloid cells mediating a spatiotemporal balance of pro- and anti-inflammatory responses, as correlates of efficacy in female macaques vaccinated with the DNA/ALVAC/gp120/Alum platform.
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- 2023
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4. Complete Rescue of HTLV-1p12KO Infectivity by Depletion of Monocytes Together with NK and CD8+ T Cells
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Anna Gutowska, Sarkis Sarkis, Mohammad Arif Rahman, Katherine C. Goldfarbmuren, Ramona Moles, Massimiliano Bissa, Melvin Doster, Robyn Washington-Parks, Katherine McKinnon, Isabela Silva de Castro, Luca Schifanella, Genoveffa Franchini, and Cynthia A. Pise-Masison
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HTLV-1 ,NK cells ,CD8 ,chemokines ,cytokines ,Adult-T-cell Leukemia/Lymphoma ,Medicine - Abstract
The transient depletion of monocytes alone prior to exposure of macaques to HTLV-1 enhances both HTLV-1WT (wild type) and HTLV-1p12KO (Orf-1 knockout) infectivity, but seroconversion to either virus is not sustained over time, suggesting a progressive decrease in virus expression. These results raise the hypotheses that either HTLV-1 persistence depends on a monocyte reservoir or monocyte depletion provides a transient immune evasion benefit. To test these hypotheses, we simultaneously depleted NK cells, CD8+ T cells, and monocytes (triple depletion) prior to exposure to HTLV-1WT or HTLV-1p12KO. Remarkably, triple depletion resulted in exacerbation of infection by both viruses and complete rescue of HTLV-1p12KO infectivity. Following triple depletion, we observed rapid and sustained seroconversion, high titers of antibodies against HTLV-1 p24Gag, and frequent detection of viral DNA in the blood and tissues of all animals when compared with depletion of only CD8+ and NK cells, or monocytes alone. The infection of macaques with HTLV-1WT or HTLV-1p12KO was associated with higher plasma levels of IL-10 after 21 weeks, while IL-6, IFN-γ, IL-18, and IL-1β were only elevated in animals infected with HTLV-1WT. The repeat depletion of monocytes, NK, and CD8+ cells seven months following the first exposure to HTLV-1 did not further exacerbate viral replication. These results underscore the contribution of monocytes in orchestrating anti-viral immunity. Indeed, the absence of orf-1 expression was fully compensated by the simultaneous depletion of CD8+ T cells, NK cells, and monocytes, underlining the primary role of orf-1 in hijacking host immunity.
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- 2024
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5. Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVmac251 acquisition in macaques
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Mohammad Arif Rahman, Manuel Becerra-Flores, Yury Patskovsky, Isabela Silva de Castro, Massimiliano Bissa, Shraddha Basu, Xiaoying Shen, LaTonya D. Williams, Sarkis Sarkis, Kombo F. N’guessan, Celia LaBranche, Georgia D. Tomaras, Pyone Pyone Aye, Ronald Veazey, Dominic Paquin-Proulx, Mangala Rao, Genoveffa Franchini, and Timothy Cardozo
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SIV ,single epitope subunit vaccine ,cholera toxin B scaffold vaccine ,DNA/ALVAC vaccine ,ADCC ,efferocytosis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionAn efficacious HIV vaccine will need to elicit a complex package of innate, humoral, and cellular immune responses. This complex package of responses to vaccine candidates has been studied and yielded important results, yet it has been a recurring challenge to determine the magnitude and protective effect of specific in vivo immune responses in isolation. We therefore designed a single, viral-spike-apical, epitope-focused V2 loop immunogen to reveal individual vaccine-elicited immune factors that contribute to protection against HIV/SIV.MethodWe generated a novel vaccine by incorporating the V2 loop B-cell epitope in the cholera toxin B (CTB) scaffold and compared two new immunization regimens to a historically protective ‘standard’ vaccine regimen (SVR) consisting of 2xDNA prime boosted with 2xALVAC-SIV and 1xΔV1gp120. We immunized a cohort of macaques with 5xCTB-V2c vaccine+alum intramuscularly simultaneously with topical intrarectal vaccination of CTB-V2c vaccine without alum (5xCTB-V2/alum). In a second group, we tested a modified version of the SVR consisting of 2xDNA prime and boosted with 1xALVAC-SIV and 2xALVAC-SIV+CTB-V2/alum, (DA/CTB-V2c/alum).ResultsIn the absence of any other anti-viral antibodies, V2c epitope was highly immunogenic when incorporated in the CTB scaffold and generated highly functional anti-V2c antibodies in the vaccinated animals. 5xCTB-V2c/alum vaccination mediated non-neutralizing ADCC activity and efferocytosis, but produced low avidity, trogocytosis, and no neutralization of tier 1 virus. Furthermore, DA/CTB-V2c/alum vaccination also generated lower total ADCC activity, avidity, and neutralization compared to the SVR. These data suggest that the ΔV1gp120 boost in the SVR yielded more favorable immune responses than its CTB-V2c counterpart. Vaccination with the SVR generates CCR5- α4β7+CD4+ Th1, Th2, and Th17 cells, which are less likely to be infected by SIV/HIV and likely contributed to the protection afforded in this regimen. The 5xCTB-V2c/alum regimen likewise elicited higher circulating CCR5- α4β7+ CD4+ T cells and mucosal α4β7+ CD4+ T cells compared to the DA/CTB-V2c/alum regimen, whereas the first cell type was associated with reduced risk of viral acquisition.ConclusionTaken together, these data suggest that individual viral spike B-cell epitopes can be highly immunogenic and functional as isolated immunogens, although they might not be sufficient on their own to provide full protection against HIV/SIV infection.
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- 2023
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6. Publisher Correction: Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques
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Rahman, Mohammad Arif, Bissa, Massimiliano, Silva de Castro, Isabela, Helmold Hait, Sabrina, Stamos, James D., Bhuyan, Farzana, Hunegnaw, Ruth, Sarkis, Sarkis, Gutowska, Anna, Doster, Melvin N., Moles, Ramona, Hoang, Tanya, Miller Jenkins, Lisa M., Appella, Ettore, Venzon, David J., Choo-Wosoba, Hyoyoung, Cardozo, Timothy, Baum, Marc M., Appella, Daniel H., Robert-Guroff, Marjorie, and Franchini, Genoveffa
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- 2023
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7. In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells
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Massimiliano Bissa, Veronica Galli, Luca Schifanella, Monica Vaccari, Mohammad Arif Rahman, Giacomo Gorini, Nicolò Binello, Sarkis Sarkis, Anna Gutowska, Isabela Silva de Castro, Melvin N. Doster, Ramona Moles, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, Kombo F. N’guessan, Dominic Paquin-Proulx, Pamela A. Kozlowski, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Joshua Kramer, and Genoveffa Franchini
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IGF-1 ,HIV ,SIV ,insulin-like growth factor ,CCR5 ,CD4 ,Medicine - Abstract
At the heart of the DNA/ALVAC/gp120/alum vaccine’s efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination. We found that IGF-1 changed the hierarchy of V1/V2 epitope recognition and decreased both ADCC specific for helical V2 and efferocytosis. Remarkably, IGF-1 also reduced the expression of CCR5 on vaccine-induced CD4+ gut-homing T-cells, compensating for its negative effect on ADCC and efferocytosis and resulting in equivalent vaccine efficacy (71% with IGF-1 and 69% without).
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- 2023
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8. Complete Rescue of HTLV-1p12KO Infectivity by Depletion of Monocytes Together with NK and CD8+ T Cells
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Gutowska, Anna, primary, Sarkis, Sarkis, additional, Rahman, Mohammad Arif, additional, Goldfarbmuren, Katherine C., additional, Moles, Ramona, additional, Bissa, Massimiliano, additional, Doster, Melvin, additional, Washington-Parks, Robyn, additional, McKinnon, Katherine, additional, Silva de Castro, Isabela, additional, Schifanella, Luca, additional, Franchini, Genoveffa, additional, and Pise-Masison, Cynthia A., additional
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- 2024
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9. Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates
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Silva de Castro, Isabela, Gorini, Giacomo, Mason, Rosemarie, Gorman, Jason, Bissa, Massimiliano, Rahman, Mohammad A., Arakelyan, Anush, Kalisz, Irene, Whitney, Stephen, Becerra-Flores, Manuel, Ni, Eric, Peachman, Kristina, Trinh, Hung V., Read, Michael, Liu, Mei-Hue, Van Ryk, Donald, Paquin-Proulx, Dominic, Shubin, Zhanna, Tuyishime, Marina, Peele, Jennifer, Ahmadi, Mohammed S., Verardi, Raffaello, Hill, Juliane, Beddall, Margaret, Nguyen, Richard, Stamos, James D., Fujikawa, Dai, Min, Susie, Schifanella, Luca, Vaccari, Monica, Galli, Veronica, Doster, Melvin N., Liyanage, Namal P.M., Sarkis, Sarkis, Caccuri, Francesca, LaBranche, Celia, Montefiori, David C., Tomaras, Georgia D., Shen, Xiaoying, Rosati, Margherita, Felber, Barbara K., Pavlakis, George N., Venzon, David J., Magnanelli, William, Breed, Matthew, Kramer, Josh, Keele, Brandon F., Eller, Michael A., Cicala, Claudia, Arthos, James, Ferrari, Guido, Margolis, Leonid, Robert-Guroff, Marjorie, Kwong, Peter D., Roederer, Mario, Rao, Mangala, Cardozo, Timothy J., and Franchini, Genoveffa
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- 2021
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10. Transient Viral Activation in Human T Cell Leukemia Virus Type 1-Infected Macaques Treated With Pomalidomide
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Anna Gutowska, Katherine McKinnon, Sarkis Sarkis, Melvin N. Doster, Massimiliano Bissa, Ramona Moles, James D. Stamos, Mohammad Arif Rahman, Robyn Washington-Parks, David Davis, Robert Yarchoan, Genoveffa Franchini, and Cynthia A. Pise-Masison
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human T cell leukemia virus ,HTLV-1 ,pomalidomide ,CTL and NK cell activation ,macaque model ,immune activation ,Medicine (General) ,R5-920 - Abstract
Human T cell leukemia virus type 1 (HTLV-1) persists in the host despite a vigorous immune response that includes cytotoxic T cells (CTL) and natural killer (NK) cells, suggesting the virus has developed effective mechanisms to counteract host immune surveillance. We recently showed that in vitro treatment of HTLV-1-infected cells with the drug pomalidomide (Pom) increases surface expression of MHC-I, ICAM-1, and B7-2, and significantly increases the susceptibility of HTLV-1-infected cells to NK and CTL killing, which is dependent on viral orf-I expression. We reasoned that by restoring cell surface expression of these molecules, Pom treatment has the potential to reduce virus burden by rendering infected cells susceptible to NK and CTL killing. We used the rhesus macaque model to determine if Pom treatment of infected individuals activates the host immune system and allows recognition and clearance of HTLV-1-infected cells. We administered Pom (0.2 mg/kg) orally to four HTLV-1-infected macaques over a 24 day period and collected blood, urine, and bone marrow samples throughout the study. Pom treatment caused immune activation in all four animals and a marked increase in proliferating CD4+, CD8+, and NK cells as measured by Ki-67+ cells. Activation markers HLA-DR, CD11b, and CD69 also increased during treatment. While we detected an increased frequency of cells with a memory CD8+ phenotype, we also found an increased frequency of cells with a Treg-like phenotype. Concomitant with immune activation, the frequency of detection of viral DNA and the HTLV-1-specific humoral response increased as well. In 3 of 4 animals, Pom treatment resulted in increased antibodies to HTLV-1 antigens as measured by western blot and p24Gag ELISA. Consistent with Pom inducing immune and HTLV-1 activation, we measured elevated leukotrienes LTB4 and LTE4 in the urine of all animals. Despite an increase in plasma LTB4, no significant changes in plasma cytokine/chemokine levels were detected. In all cases, however, cellular populations, LTB4, and LTE4 decreased to baseline or lower levels 2 weeks after cessation of treatment. These results indicated that Pom treatment induces a transient HTLV-1-specific immune activation in infected individuals, but also suggest Pom may not be effective as a single-agent therapeutic.
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- 2022
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11. NK cells and monocytes modulate primary HTLV-1 infection.
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Ramona Moles, Sarkis Sarkis, Veronica Galli, Maria Omsland, Maria Artesi, Massimiliano Bissa, Katherine McKinnon, Sophia Brown, Vincent Hahaut, Robyn Washington-Parks, Joshua Welsh, David J Venzon, Anna Gutowska, Melvin N Doster, Matthew W Breed, Kristin E Killoran, Joshua Kramer, Jennifer Jones, Marcin Moniuszko, Anne Van den Broeke, Cynthia A Pise-Masison, and Genoveffa Franchini
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
We investigated the impact of monocytes, NK cells, and CD8+ T-cells in primary HTLV-1 infection by depleting cell subsets and exposing macaques to either HTLV-1 wild type (HTLV-1WT) or to the HTLV-1p12KO mutant unable to infect replete animals due to a single point mutation in orf-I that inhibits its expression. The orf-I encoded p8/p12 proteins counteract cytotoxic NK and CD8+ T-cells and favor viral DNA persistence in monocytes. Double NK and CD8+ T-cells or CD8 depletion alone accelerated seroconversion in all animals exposed to HTLV-1WT. In contrast, HTLV-1p12KO infectivity was fully restored only when NK cells were also depleted, demonstrating a critical role of NK cells in primary infection. Monocyte/macrophage depletion resulted in accelerated seroconversion in all animals exposed to HTLV-1WT, but antibody titers to the virus were low and not sustained. Seroconversion did not occur in most animals exposed to HTLV-1p12KO. In vitro experiments in human primary monocytes or THP-1 cells comparing HTLV-1WT and HTLV-1p12KO demonstrated that orf-I expression is associated with inhibition of inflammasome activation in primary cells, with increased CD47 "don't-eat-me" signal surface expression in virus infected cells and decreased monocyte engulfment of infected cells. Collectively, our data demonstrate a critical role for innate NK cells in primary infection and suggest a dual role of monocytes in primary infection. On one hand, orf-I expression increases the chances of viral transmission by sparing infected cells from efferocytosis, and on the other may protect the engulfed infected cells by modulating inflammasome activation. These data also suggest that, once infection is established, the stoichiometry of orf-I expression may contribute to the chronic inflammation observed in HTLV-1 infection by modulating monocyte efferocytosis.
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- 2022
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12. Complete Rescue of HTLV-1 p12KO Infectivity by Depletion of Monocytes Together with NK and CD8 + T Cells.
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Gutowska, Anna, Sarkis, Sarkis, Rahman, Mohammad Arif, Goldfarbmuren, Katherine C., Moles, Ramona, Bissa, Massimiliano, Doster, Melvin, Washington-Parks, Robyn, McKinnon, Katherine, Silva de Castro, Isabela, Schifanella, Luca, Franchini, Genoveffa, and Pise-Masison, Cynthia A.
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MONOCYTES ,KILLER cells ,T cells ,CD8 antigen ,VIRAL DNA ,ANTIBODY titer ,ANIMAL rescue - Abstract
The transient depletion of monocytes alone prior to exposure of macaques to HTLV-1 enhances both HTLV-1
WT (wild type) and HTLV-1p12KO (Orf-1 knockout) infectivity, but seroconversion to either virus is not sustained over time, suggesting a progressive decrease in virus expression. These results raise the hypotheses that either HTLV-1 persistence depends on a monocyte reservoir or monocyte depletion provides a transient immune evasion benefit. To test these hypotheses, we simultaneously depleted NK cells, CD8+ T cells, and monocytes (triple depletion) prior to exposure to HTLV-1WT or HTLV-1p12KO . Remarkably, triple depletion resulted in exacerbation of infection by both viruses and complete rescue of HTLV-1p12KO infectivity. Following triple depletion, we observed rapid and sustained seroconversion, high titers of antibodies against HTLV-1 p24Gag, and frequent detection of viral DNA in the blood and tissues of all animals when compared with depletion of only CD8+ and NK cells, or monocytes alone. The infection of macaques with HTLV-1WT or HTLV-1p12KO was associated with higher plasma levels of IL-10 after 21 weeks, while IL-6, IFN-γ, IL-18, and IL-1β were only elevated in animals infected with HTLV-1WT . The repeat depletion of monocytes, NK, and CD8+ cells seven months following the first exposure to HTLV-1 did not further exacerbate viral replication. These results underscore the contribution of monocytes in orchestrating anti-viral immunity. Indeed, the absence of orf-1 expression was fully compensated by the simultaneous depletion of CD8+ T cells, NK cells, and monocytes, underlining the primary role of orf-1 in hijacking host immunity. [ABSTRACT FROM AUTHOR]- Published
- 2024
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13. 3D porous nickel nanosheet arrays as an advanced electrode material for high energy hybrid supercapacitors
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Sarkis, Sarkis and Huang, Xintang
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- 2020
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14. In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells
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Bissa, Massimiliano, primary, Galli, Veronica, additional, Schifanella, Luca, additional, Vaccari, Monica, additional, Rahman, Mohammad Arif, additional, Gorini, Giacomo, additional, Binello, Nicolò, additional, Sarkis, Sarkis, additional, Gutowska, Anna, additional, Silva de Castro, Isabela, additional, Doster, Melvin N., additional, Moles, Ramona, additional, Ferrari, Guido, additional, Shen, Xiaoying, additional, Tomaras, Georgia D., additional, Montefiori, David C., additional, N’guessan, Kombo F., additional, Paquin-Proulx, Dominic, additional, Kozlowski, Pamela A., additional, Venzon, David J., additional, Choo-Wosoba, Hyoyoung, additional, Breed, Matthew W., additional, Kramer, Joshua, additional, and Franchini, Genoveffa, additional
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- 2023
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15. Functional properties and sequence variation of HTLV-1 p13
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Maria Omsland, Micol Silic-Benussi, Ramona Moles, Sarkis Sarkis, Damian F. J. Purcell, David Yurick, Georges Khoury, Donna M. D’Agostino, Vincenzo Ciminale, and Genoveffa Franchini
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Human T cell leukemia virus type-1 ,HTLV-1 ,HTLV-1C ,p13 ,Mitochondria ,Cell death ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Human T cell leukemia virus type-1 (HTLV-1) was the first retrovirus found to cause cancer in humans, but the mechanisms that drive the development of leukemia and other diseases associated with HTLV-1 infection remain to be fully understood. This review describes the functional properties of p13, an 87-amino acid protein coded by HTLV-1 open reading frame II (orf-II). p13 is mainly localized in the inner membrane of the mitochondria, where it induces potassium (K+) influx and reactive oxygen species (ROS) production, which can trigger either proliferation or apoptosis, depending on the ROS setpoint of the cell. Recent evidence indicates that p13 may influence the cell’s innate immune response to viral infection and the infected cell phenotype. Association of the HTLV-1 transcriptional activator, Tax, with p13 increases p13’s stability, leads to its partial co-localization with Tax in nuclear speckles, and reduces the ability of Tax to interact with the transcription cofactor CBP/p300. Comparison of p13 sequences isolated from HTLV-1-infected individuals revealed a small number of amino acid variations in the domains controlling the subcellular localization of the protein. Disruptive mutations of p13 were found in samples obtained from asymptomatic patients with low proviral load. p13 sequences of HTLV-1 subtype C isolates from indigenous Australian patients showed a high degree of identity among each other, with all samples containing a pattern of 5 amino acids that distinguished them from other subtypes. Further characterization of p13’s functional properties and sequence variants may lead to a deeper understanding of the impact of p13 as a contributor to the clinical manifestations of HTLV-1 infection.
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- 2020
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16. Role of HTLV-1 orf-I encoded proteins in viral transmission and persistence
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Sarkis Sarkis, Veronica Galli, Ramona Moles, David Yurick, Georges Khoury, Damian F. J. Purcell, Genoveffa Franchini, and Cynthia A. Pise-Masison
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HTLV-1 ,STLV-1 ,orf-I ,p12/p8 ,rex-orf-I ,Adult T-cell leukemia/lymphoma ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract The human T cell leukemia virus type 1 (HTVL-1), first reported in 1980 by Robert Gallo’s group, is the etiologic agent of both cancer and inflammatory diseases. Despite approximately 40 years of investigation, the prognosis for afflicted patients remains poor with no effective treatments. The virus persists in the infected host by evading the host immune response and inducing proliferation of infected CD4+ T-cells. Here, we will review the role that viral orf-I protein products play in altering intracellular signaling, protein expression and cell–cell communication in order to escape immune recognition and promote T-cell proliferation. We will also review studies of orf-I mutations found in infected patients and their potential impact on viral load, transmission and persistence. Finally, we will compare the orf-I gene in HTLV-1 subtypes as well as related STLV-1.
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- 2019
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17. p30 protein: a critical regulator of HTLV-1 viral latency and host immunity
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Ramona Moles, Sarkis Sarkis, Veronica Galli, Maria Omsland, Damian F. J. Purcell, David Yurick, Georges Khoury, Cynthia A. Pise-Masison, and Genoveffa Franchini
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HTLV-1 ,orf-II ,p30 ,Tax-orf-II ,Adult T-cell leukemia/lymphoma ,ATLL ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract The extraordinarily high prevalence of HTLV-1 subtype C (HTLV-1C) in some isolated indigenous communities in Oceania and the severity of the health conditions associated with the virus impress the great need for basic and translational research to prevent and treat HTLV-1 infection. The genome of the virus’s most common subtype, HTLV-1A, encodes structural, enzymatic, and regulatory proteins that contribute to viral persistence and pathogenesis. Among these is the p30 protein encoded by the doubly spliced Tax-orf II mRNA, a nuclear/nucleolar protein with both transcriptional and post-transcriptional activity. The p30 protein inhibits the productive replication cycle via nuclear retention of the mRNA that encodes for both the viral transcriptional trans-activator Tax, and the Rex proteins that regulate the transport of incompletely spliced viral mRNA to the cytoplasm. In myeloid cells, p30 inhibits the PU-1 transcription factor that regulates interferon expression and is a critical mediator of innate and adaptive immunity. Furthermore, p30 alters gene expression, cell cycle progression, and DNA damage responses in T-cells, raising the hypothesis that p30 may directly contribute to T cell transformation. By fine-tuning viral expression while also inhibiting host innate responses, p30 is likely essential for viral infection and persistence. This concept is supported by the finding that macaques, a natural host for the closely genetically related simian T-cell leukemia virus 1 (STLV-1), exposed to an HTLV-1 knockout for p30 expression by a single point mutation do not became infected unless reversion and selection of the wild type HTLV-1 genotype occurs. All together, these data suggest that inhibition of p30 may help to curb and eventually eradicate viral infection by exposing infected cells to an effective host immune response.
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- 2019
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18. Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques
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Mohammad Arif Rahman, Massimiliano Bissa, Isabela Silva de Castro, Sabrina Helmold Hait, James D. Stamos, Farzana Bhuyan, Ruth Hunegnaw, Sarkis Sarkis, Anna Gutowska, Melvin N. Doster, Ramona Moles, Tanya Hoang, Lisa M. Miller Jenkins, Ettore Appella, David J. Venzon, Hyoyoung Choo-Wosoba, Timothy Cardozo, Marc M. Baum, Daniel H. Appella, Marjorie Robert-Guroff, and Genoveffa Franchini
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Microbiology (medical) ,Immunology ,Genetics ,Cell Biology ,Applied Microbiology and Biotechnology ,Microbiology - Abstract
The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV)mac251 acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIVmac251, 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected. In an arm of 18 vaccinated-only animals without microbicide, 40% of macaques remained uninfected. The combined SAMT-247/vaccine regimen was significantly more effective than vaccination alone. By analysing immune correlates of protection, we show that, by increasing zinc availability, SAMT-247 increases natural killer cytotoxicity and monocyte efferocytosis, and decreases T-cell activation to augment vaccine-induced protection.
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- 2023
19. Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates
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Isabela Silva de Castro, Giacomo Gorini, Rosemarie Mason, Jason Gorman, Massimiliano Bissa, Mohammad A. Rahman, Anush Arakelyan, Irene Kalisz, Stephen Whitney, Manuel Becerra-Flores, Eric Ni, Kristina Peachman, Hung V. Trinh, Michael Read, Mei-Hue Liu, Donald Van Ryk, Dominic Paquin-Proulx, Zhanna Shubin, Marina Tuyishime, Jennifer Peele, Mohammed S. Ahmadi, Raffaello Verardi, Juliane Hill, Margaret Beddall, Richard Nguyen, James D. Stamos, Dai Fujikawa, Susie Min, Luca Schifanella, Monica Vaccari, Veronica Galli, Melvin N. Doster, Namal P.M. Liyanage, Sarkis Sarkis, Francesca Caccuri, Celia LaBranche, David C. Montefiori, Georgia D. Tomaras, Xiaoying Shen, Margherita Rosati, Barbara K. Felber, George N. Pavlakis, David J. Venzon, William Magnanelli, Matthew Breed, Josh Kramer, Brandon F. Keele, Michael A. Eller, Claudia Cicala, James Arthos, Guido Ferrari, Leonid Margolis, Marjorie Robert-Guroff, Peter D. Kwong, Mario Roederer, Mangala Rao, Timothy J. Cardozo, and Genoveffa Franchini
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Immunology ,molecular structure ,virology ,Science - Abstract
Summary: The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the α4β7 integrin. SIV vaccines engineered to delete V1 and favor an α helix, rather than a β sheet V2 conformation, induced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing V2 in the β sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.
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- 2021
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20. A potential robust antiviral defense state in the common vampire bat: Expression, induction and molecular characterization of the three interferon-stimulated genes -OAS1, ADAR1 and PKR
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Sarkis, Sarkis, Dabo, Stéphanie, Lise, Marie-Claude, Neuveut, Christine, Meurs, Eliane F., Lacoste, Vincent, and Lavergne, Anne
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- 2018
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21. Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVmac251 acquisition in macaques
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Rahman, Mohammad Arif, primary, Becerra-Flores, Manuel, additional, Patskovsky, Yury, additional, Silva de Castro, Isabela, additional, Bissa, Massimiliano, additional, Basu, Shraddha, additional, Shen, Xiaoying, additional, Williams, LaTonya D., additional, Sarkis, Sarkis, additional, N’guessan, Kombo F., additional, LaBranche, Celia, additional, Tomaras, Georgia D., additional, Aye, Pyone Pyone, additional, Veazey, Ronald, additional, Paquin-Proulx, Dominic, additional, Rao, Mangala, additional, Franchini, Genoveffa, additional, and Cardozo, Timothy, additional
- Published
- 2023
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22. Functional properties and sequence variation of HTLV-1 p13
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Omsland, Maria, Silic-Benussi, Micol, Moles, Ramona, Sarkis, Sarkis, Purcell, Damian F. J., Yurick, David, Khoury, Georges, D’Agostino, Donna M., Ciminale, Vincenzo, and Franchini, Genoveffa
- Published
- 2020
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23. p30 protein: a critical regulator of HTLV-1 viral latency and host immunity
- Author
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Moles, Ramona, Sarkis, Sarkis, Galli, Veronica, Omsland, Maria, Purcell, Damian F. J., Yurick, David, Khoury, Georges, Pise-Masison, Cynthia A., and Franchini, Genoveffa
- Published
- 2019
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24. In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4 + T-Cells.
- Author
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Bissa, Massimiliano, Galli, Veronica, Schifanella, Luca, Vaccari, Monica, Rahman, Mohammad Arif, Gorini, Giacomo, Binello, Nicolò, Sarkis, Sarkis, Gutowska, Anna, Silva de Castro, Isabela, Doster, Melvin N., Moles, Ramona, Ferrari, Guido, Shen, Xiaoying, Tomaras, Georgia D., Montefiori, David C., N'guessan, Kombo F., Paquin-Proulx, Dominic, Kozlowski, Pamela A., and Venzon, David J.
- Subjects
SOMATOMEDIN C ,CHEMOKINE receptors ,T cells ,VACCINE effectiveness ,CD4 antigen - Abstract
At the heart of the DNA/ALVAC/gp120/alum vaccine's efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIV
mac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination. We found that IGF-1 changed the hierarchy of V1/V2 epitope recognition and decreased both ADCC specific for helical V2 and efferocytosis. Remarkably, IGF-1 also reduced the expression of CCR5 on vaccine-induced CD4+ gut-homing T-cells, compensating for its negative effect on ADCC and efferocytosis and resulting in equivalent vaccine efficacy (71% with IGF-1 and 69% without). [ABSTRACT FROM AUTHOR]- Published
- 2023
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25. Publisher Correction: Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques
- Author
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Mohammad Arif Rahman, Massimiliano Bissa, Isabela Silva de Castro, Sabrina Helmold Hait, James D. Stamos, Farzana Bhuyan, Ruth Hunegnaw, Sarkis Sarkis, Anna Gutowska, Melvin N. Doster, Ramona Moles, Tanya Hoang, Lisa M. Miller Jenkins, Ettore Appella, David J. Venzon, Hyoyoung Choo-Wosoba, Timothy Cardozo, Marc M. Baum, Daniel H. Appella, Marjorie Robert-Guroff, and Genoveffa Franchini
- Subjects
Microbiology (medical) ,Immunology ,Genetics ,Cell Biology ,Applied Microbiology and Biotechnology ,Microbiology - Published
- 2023
26. Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVmac251 acquisition in macaques.
- Author
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Rahman, Mohammad Arif, Becerra-Flores, Manuel, Patskovsky, Yury, de Castro, Isabela Silva, Bissa, Massimiliano, Basu, Shraddha, Xiaoying Shen, Williams, LaTonya D., Sarkis, Sarkis, N'guessan, Kombo F., LaBranche, Celia, Tomaras, Georgia D., Aye, Pyone Pyone, Veazey, Ronald, Paquin-Proulx, Dominic, Rao, Mangala, Franchini, Genoveffa, and Cardozo, Timothy
- Subjects
CHOLERA toxin ,HUMORAL immunity ,MACAQUES ,T helper cells ,VACCINE effectiveness ,T cells - Abstract
Introduction: An efficacious HIV vaccine will need to elicit a complex package of innate, humoral, and cellular immune responses. This complex package of responses to vaccine candidates has been studied and yielded important results, yet it has been a recurring challenge to determine the magnitude and protective effect of specific in vivo immune responses in isolation. We therefore designed a single, viral-spike-apical, epitope-focused V2 loop immunogen to reveal individual vaccine-elicited immune factors that contribute to protection against HIV/SIV. Method: We generated a novel vaccine by incorporating the V2 loop B-cell epitope in the cholera toxin B (CTB) scaffold and compared two new immunization regimens to a historically protective 'standard' vaccine regimen (SVR) consisting of 2xDNA prime boosted with 2xALVAC-SIV and 1xΔV1gp120. We immunized a cohort of macaques with 5xCTB-V2c vaccine+alum intramuscularly simultaneously with topical intrarectal vaccination of CTB-V2c vaccine without alum (5xCTB-V2/alum). In a second group, we tested a modified version of the SVR consisting of 2xDNA prime and boosted with 1xALVAC-SIV and 2xALVAC-SIV
+ CTB-V2/alum, (DA/CTB-V2c/alum). Results: In the absence of any other anti-viral antibodies, V2c epitope was highly immunogenic when incorporated in the CTB scaffold and generated highly functional anti-V2c antibodies in the vaccinated animals. 5xCTB-V2c/alum vaccination mediated non-neutralizing ADCC activity and efferocytosis, but produced low avidity, trogocytosis, and no neutralization of tier 1 virus. Furthermore, DA/CTB-V2c/alum vaccination also generated lower total ADCC activity, avidity, and neutralization compared to the SVR. These data suggest that the ΔV1gp120 boost in the SVR yielded more favorable immune responses than its CTB-V2c counterpart. Vaccination with the SVR generates CCR5-α4β7+ CD4+ Th1, Th2, and Th17 cells, which are less likely to be infected by SIV/HIV and likely contributed to the protection afforded in this regimen. The 5xCTB-V2c/alum regimen likewise elicited higher circulating CCR5-α4β7+ CD4+ T cells and mucosal α4β7+ CD4+ T cells compared to the DA/CTB-V2c/alum regimen, whereas the first cell type was associated with reduced risk of viral acquisition. Conclusion: Taken together, these data suggest that individual viral spike B-cell epitopes can be highly immunogenic and functional as isolated immunogens, although they might not be sufficient on their own to provide full protection against HIV/SIV infection. [ABSTRACT FROM AUTHOR]- Published
- 2023
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27. Transient Viral Activation in Human T Cell Leukemia Virus Type 1-Infected Macaques Treated With Pomalidomide
- Author
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Gutowska, Anna, primary, McKinnon, Katherine, additional, Sarkis, Sarkis, additional, Doster, Melvin N., additional, Bissa, Massimiliano, additional, Moles, Ramona, additional, Stamos, James D., additional, Rahman, Mohammad Arif, additional, Washington-Parks, Robyn, additional, Davis, David, additional, Yarchoan, Robert, additional, Franchini, Genoveffa, additional, and Pise-Masison, Cynthia A., additional
- Published
- 2022
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28. NK cells and monocytes modulate primary HTLV-1 infection
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Moles, Ramona, primary, Sarkis, Sarkis, additional, Galli, Veronica, additional, Omsland, Maria, additional, Artesi, Maria, additional, Bissa, Massimiliano, additional, McKinnon, Katherine, additional, Brown, Sophia, additional, Hahaut, Vincent, additional, Washington-Parks, Robyn, additional, Welsh, Joshua, additional, Venzon, David J., additional, Gutowska, Anna, additional, Doster, Melvin N., additional, Breed, Matthew W., additional, Killoran, Kristin E., additional, Kramer, Joshua, additional, Jones, Jennifer, additional, Moniuszko, Marcin, additional, Van den Broeke, Anne, additional, Pise-Masison, Cynthia A., additional, and Franchini, Genoveffa, additional
- Published
- 2022
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29. Cobalt Nanorods as Transition Metal Electrode Materials for Asymmetric Supercapacitor Applications
- Author
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Xintang Huang and Sarkis Sarkis
- Subjects
Supercapacitor ,Electrode material ,Materials science ,Annealing (metallurgy) ,chemistry.chemical_element ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,General Energy ,chemistry ,Transition metal ,Chemical engineering ,Electrode ,Nanorod ,Physical and Theoretical Chemistry ,Porosity ,Cobalt - Abstract
A porous cobalt nanorods (Co-NRs) structure is successfully synthesized via annealing of Co(OH)2 nanorods at 350 °C with the presence of ethanol glycol (EG). The Co-NRs@Ni foam electrode displayed ...
- Published
- 2020
30. Role of HTLV-1 orf-I encoded proteins in viral transmission and persistence
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Veronica Galli, Ramona Moles, Georges Khoury, Cynthia A. Pise-Masison, Sarkis Sarkis, David Yurick, Genoveffa Franchini, and Damian F. J. Purcell
- Subjects
CD4-Positive T-Lymphocytes ,lcsh:Immunologic diseases. Allergy ,rex-orf-I ,viruses ,T-cell leukemia ,orf-I ,Review ,ATLL ,Virus ,p12/p8 ,03 medical and health sciences ,Immune system ,Virology ,MHC class I ,Humans ,Viral Regulatory and Accessory Proteins ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Human T-lymphotropic virus 1 ,HTLV-1 associated myelopathy/tropical spastic paraparesis ,biology ,030306 microbiology ,Transmission (medicine) ,Immune evasion ,STLV-1 ,Viral Load ,biology.organism_classification ,HTLV-I Infections ,Paraparesis, Tropical Spastic ,3. Good health ,Infectious Diseases ,HTLV-1 ,Adult T-cell leukemia/lymphoma ,biology.protein ,Antibody ,HAM/TSP ,Simian T-lymphotropic virus 1 ,lcsh:RC581-607 ,Viral load - Abstract
The human T cell leukemia virus type 1 (HTVL-1), first reported in 1980 by Robert Gallo’s group, is the etiologic agent of both cancer and inflammatory diseases. Despite approximately 40 years of investigation, the prognosis for afflicted patients remains poor with no effective treatments. The virus persists in the infected host by evading the host immune response and inducing proliferation of infected CD4+T-cells. Here, we will review the role that viralorf-Iprotein products play in altering intracellular signaling, protein expression and cell–cell communication in order to escape immune recognition and promote T-cell proliferation. We will also review studies oforf-Imutations found in infected patients and their potential impact on viral load, transmission and persistence. Finally, we will compare theorf-Igene in HTLV-1 subtypes as well as related STLV-1.
- Published
- 2019
31. p30 protein: a critical regulator of HTLV-1 viral latency and host immunity
- Author
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Genoveffa Franchini, Maria Omsland, Georges Khoury, Ramona Moles, Sarkis Sarkis, Veronica Galli, Cynthia A. Pise-Masison, David Yurick, and Damian F. J. Purcell
- Subjects
Gene Expression Regulation, Viral ,lcsh:Immunologic diseases. Allergy ,p30 ,Genotype ,viruses ,Adaptive immunity ,Retroviridae Proteins ,Gene Expression ,Review ,ATLL ,Virus ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Interferon ,Virology ,Virus latency ,medicine ,Animals ,Humans ,030304 developmental biology ,Regulation of gene expression ,Innate immunity ,0303 health sciences ,Human T-lymphotropic virus 1 ,Innate immune system ,HTLV-1 associated myelopathy/tropical spastic paraparesis ,biology ,orf-II ,Acquired immune system ,biology.organism_classification ,medicine.disease ,HTLV-I Infections ,3. Good health ,Virus Latency ,Infectious Diseases ,Tax-orf-II ,HTLV-1 ,030220 oncology & carcinogenesis ,Adult T-cell leukemia/lymphoma ,Macaca ,RNA, Viral ,HAM/TSP ,lcsh:RC581-607 ,medicine.drug - Abstract
The extraordinarily high prevalence of HTLV-1 subtype C (HTLV-1C) in some isolated indigenous communities in Oceania and the severity of the health conditions associated with the virus impress the great need for basic and translational research to prevent and treat HTLV-1 infection. The genome of the virus’s most common subtype, HTLV-1A, encodes structural, enzymatic, and regulatory proteins that contribute to viral persistence and pathogenesis. Among these is the p30 protein encoded by the doubly splicedTax-orf IImRNA, a nuclear/nucleolar protein with both transcriptional and post-transcriptional activity. The p30 protein inhibits the productive replication cycle via nuclear retention of the mRNA that encodes for both the viral transcriptional trans-activator Tax, and the Rex proteins that regulate the transport of incompletely spliced viral mRNA to the cytoplasm. In myeloid cells, p30 inhibits the PU-1 transcription factor that regulates interferon expression and is a critical mediator of innate and adaptive immunity. Furthermore, p30 alters gene expression, cell cycle progression, and DNA damage responses in T-cells, raising the hypothesis that p30 may directly contribute to T cell transformation. By fine-tuning viral expression while also inhibiting host innate responses, p30 is likely essential for viral infection and persistence. This concept is supported by the finding that macaques, a natural host for the closely genetically related simian T-cell leukemia virus 1 (STLV-1), exposed to an HTLV-1 knockout for p30 expression by a single point mutation do not became infected unless reversion and selection of the wild type HTLV-1 genotype occurs. All together, these data suggest that inhibition of p30 may help to curb and eventually eradicate viral infection by exposing infected cells to an effective host immune response.
- Published
- 2019
32. NK cells and monocytes modulate primary HTLV-1 infection
- Author
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Ramona Moles, Sarkis Sarkis, Veronica Galli, Maria Omsland, Maria Artesi, Massimiliano Bissa, Katherine McKinnon, Sophia Brown, Vincent Hahaut, Robyn Washington-Parks, Joshua Welsh, David J. Venzon, Anna Gutowska, Melvin N. Doster, Matthew W. Breed, Kristin E. Killoran, Joshua Kramer, Jennifer Jones, Marcin Moniuszko, Anne Van den Broeke, Cynthia A. Pise-Masison, and Genoveffa Franchini
- Subjects
Killer Cells, Natural ,Human T-lymphotropic virus 1 ,Inflammasomes ,viruses ,Virology ,Immunology ,Genetics ,Animals ,Parasitology ,Molecular Biology ,Microbiology ,HTLV-I Infections ,Monocytes - Abstract
We investigated the impact of monocytes, NK cells, and CD8+ T-cells in primary HTLV-1 infection by depleting cell subsets and exposing macaques to either HTLV-1 wild type (HTLV-1WT) or to the HTLV-1p12KO mutant unable to infect replete animals due to a single point mutation in orf-I that inhibits its expression. The orf-I encoded p8/p12 proteins counteract cytotoxic NK and CD8+ T-cells and favor viral DNA persistence in monocytes. Double NK and CD8+ T-cells or CD8 depletion alone accelerated seroconversion in all animals exposed to HTLV-1WT. In contrast, HTLV-1p12KO infectivity was fully restored only when NK cells were also depleted, demonstrating a critical role of NK cells in primary infection. Monocyte/macrophage depletion resulted in accelerated seroconversion in all animals exposed to HTLV-1WT, but antibody titers to the virus were low and not sustained. Seroconversion did not occur in most animals exposed to HTLV-1p12KO. In vitro experiments in human primary monocytes or THP-1 cells comparing HTLV-1WT and HTLV-1p12KO demonstrated that orf-I expression is associated with inhibition of inflammasome activation in primary cells, with increased CD47 “don’t-eat-me” signal surface expression in virus infected cells and decreased monocyte engulfment of infected cells. Collectively, our data demonstrate a critical role for innate NK cells in primary infection and suggest a dual role of monocytes in primary infection. On one hand, orf-I expression increases the chances of viral transmission by sparing infected cells from efferocytosis, and on the other may protect the engulfed infected cells by modulating inflammasome activation. These data also suggest that, once infection is established, the stoichiometry of orf-I expression may contribute to the chronic inflammation observed in HTLV-1 infection by modulating monocyte efferocytosis.
- Published
- 2021
33. Cobalt Nanorods as Transition Metal Electrode Materials for Asymmetric Supercapacitor Applications
- Author
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Sarkis, Sarkis, primary and Huang, Xintang, additional
- Published
- 2020
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34. Anti-V2 Antibodies Virus Vulnerability Revealed by Envelope V1 Deletion in HIV Vaccine Candidates
- Author
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Silva de Castro, Isabela, primary, Gorini, Giacomo, additional, Mason, Rosemarie, additional, Gorman, Jason, additional, Bissa, Massimiliano, additional, Rahman, Mohammad Arif, additional, Arakelyan, Anush, additional, Kalisz, Irene, additional, Whitmey, Stephen, additional, Becerra-Flores, Manuel, additional, Ni, Eric, additional, Peachman, Kristina, additional, Trinh, Hung V., additional, Read, Michael, additional, Liu, Mei-Hue, additional, Van Ryk, Donald, additional, Paquin-Proulx, Dominic, additional, Shubin, Zhanna, additional, Tuyishime, Marina, additional, Peele, Jennifer, additional, Ahmadi, Mohammed S., additional, Verardi, Raffaello, additional, Hill, Juliane, additional, Beddall, Margaret, additional, Nguyen, R., additional, Stamos, James, additional, Fujikawa, Dai, additional, Min, Susie, additional, Schifanella, Luca, additional, Vaccari, Monica, additional, Galli, Veronica, additional, Doster, Melvin N., additional, Liyanage, Namal PM, additional, Sarkis, Sarkis, additional, Caccuri, Francesca, additional, LaBranche, Celia, additional, Montefiori, David C., additional, Tomaras, Georgia D., additional, Shen, Xiaoying, additional, Rosati, Margherita, additional, Felber, Barbara K., additional, Pavlakis, George N., additional, Venzon, David J., additional, Magnanelli, William, additional, Breed, Matthew, additional, Kramer, Josh, additional, Keele, Brandon F., additional, Eller, Michael A., additional, Cicala, Claudia, additional, Arthos, James, additional, Ferrari, Guido, additional, Margolis, Leonid, additional, Robert-Guroff, Marjorie, additional, Kwong, Peter D., additional, Roederer, Mario, additional, Rao, Mangala, additional, Cardozo, Timothy J., additional, and Franchini, Genoveffa, additional
- Published
- 2020
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35. MOESM2 of p30 protein: a critical regulator of HTLV-1 viral latency and host immunity
- Author
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Moles, Ramona, Sarkis, Sarkis, Galli, Veronica, Omsland, Maria, Purcell, Damian, Yurick, David, Khoury, Georges, Pise-Masison, Cynthia, and Franchini, Genoveffa
- Subjects
viruses - Abstract
Additional file 2: Figure S2. Amino acid sequence analysis of p30 from HTLV-1A infected individuals. Alignment of p30 amino acid sequences of from 160 HTLV-1A patients was used to generate a consensus. Dashes (–) indicate gaps in the amino acid alignment, asterisks (*) represent stop codons, and periods (.) represent similarity. The multi-alignment was performed with the Mega7 program using default parameters. Amino acid sequence analysis of p30 from HTLV-1A infected individuals. Alignment of p30 amino acid sequences of from 160 HTLV-1A patients was used to generate a consensus. Dashes (–) indicate gaps in the amino acid alignment, asterisks (*) represent stop codons, and periods (.) represent similarity. The multi-alignment was performed with the Mega7 program using default parameters.
- Published
- 2019
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36. MOESM1 of Role of HTLV-1 orf-I encoded proteins in viral transmission and persistence
- Author
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Sarkis, Sarkis, Galli, Veronica, Moles, Ramona, Yurick, David, Khoury, Georges, Purcell, Damian, Franchini, Genoveffa, and Pise-Masison, Cynthia
- Abstract
Additional file 1: Figure S1. Structure of the HTLV-1 proviral genome. The proviral DNA with the LTRs, and the unspliced, singly spliced and doubly spliced mRNA transcripts are shown. The names of the gene transcripts are depicted inside each specific box. Solid lines indicate the exons and the dotted lines indicate the introns.
- Published
- 2019
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37. 3D porous nickel nanosheet arrays as an advanced electrode material for high energy hybrid supercapacitors
- Author
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Xintang Huang and Sarkis Sarkis
- Subjects
Supercapacitor ,Chemistry ,General Chemical Engineering ,02 engineering and technology ,Electrolyte ,Current collector ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Capacitance ,0104 chemical sciences ,Analytical Chemistry ,Chemical engineering ,Electrode ,Nano ,Electrochemistry ,0210 nano-technology ,Current density ,Nanosheet - Abstract
3D porous nickel nanosheet arrays (Ni-NSAs@Ni foam) are prepared by a facile hydrothermal process followed by an annealing treatment. The synthesized Ni-NSAs@Ni foam offered a mesoporous nano structure. First, Ni(OH)2 nanosheet arrays on Ni foam are synthesized by a hydrothermal process. Then, the Ni(OH)2 nanosheet arrays are transformed to Ni-NSAs@Ni foam via horizontal furnace tube. The Ni-NSAs@Ni foam electrode shows a high areal capacitance 4683.6 mF cm−2 at a current density of 1 mA cm−2, a capacitance retention of 80.8% at 10 mA cm−2, low internal resistance Rs~0.75 Ω and a retention ratio of 95.8% after 20,000 charge/discharge cycles. The capacitance of Ni-NSAs@Ni foam is much higher than that of the Ni(OH)2 nanosheet arrays. The outstanding electrochemical characteristic performances of the Ni-NSAs@Ni foam can be ascribed to the 3D porous nano structures of Ni-NSAs@Ni foam, which can offer short diffusion routes for charge carriers (electrons and ions), large active areas between the interface of the electrode/electrolyte and the low internal resistance between grown Ni-NSAs@Ni foam and the conductive current collector. Its hybrid supercapacitor device is assembled by using the Ni-NSAs@Ni foam as the positive electrode and activated carbon AC@Ni foam as the negative electrode. The hybrid supercapacitor device reaches an ultra-high energy density of 141.04 Wh kg−1 and a power density of 226.14 W kg−1 at 1 mA cm−2. The remarkable pseudocapacitive performance of Ni-NSAs@Ni foam electrode shows its great potential in applications of energy storage and conversion devices.
- Published
- 2020
38. A potential robust antiviral defense state in the common vampire bat: Expression, induction and molecular characterization of the three interferon-stimulated genes -OAS1, ADAR1 and PKR
- Author
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Stéphanie Dabo, Christine Neuveut, Vincent Lacoste, Marie-Claude Lise, Eliane F. Meurs, Anne Lavergne, Sarkis Sarkis, Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hépacivirus et Immunité innée, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This study was conducted within the CAROLIA and BATIMMUNE programs. CAROLIA was supported by European funds (ERDF/FEDER, 31575) and assistance from the Région Guyane and the Direction Régionale pour la Recherche et la Technologie. BATIMMUNE was funded by the Institut Pasteur through a Transversal Research Program (PTR499). This study also received a European Commission 'REGPOT-CT-2011-285837-STRonGer' grant within the FP7 and an 'Investissement d’Avenir' grant managed by the Agence Nationale de la Recherche (CEBA, Ref. ANR-10-LABEX-25-01)., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
- Subjects
0301 basic medicine ,Transcription, Genetic ,Adenosine Deaminase ,[SDV]Life Sciences [q-bio] ,MESH: Antiviral Agents/pharmacology ,MESH: Virus Diseases/genetics ,ISGs ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,eIF-2 Kinase ,Interferon ,Transcription (biology) ,Chiroptera ,2',5'-Oligoadenylate Synthetase ,MESH: Animals ,Innate immunity ,MESH: Transcription, Genetic/drug effects ,MESH: Transcription, Genetic/genetics ,PKR ,MESH: Adenosine Deaminase/genetics ,3. Good health ,PKR 20 ,Virus Diseases ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,medicine.drug ,Immunology ,Biology ,Desmodus rotundus ,Antiviral Agents ,OAS1a ,OAS1b ,Cell Line ,03 medical and health sciences ,MESH: Poly I-C/genetics ,ADAR1 ,MESH: Chiroptera/genetics ,medicine ,MESH: 2',5'-Oligoadenylate Synthetase/genetics ,Animals ,Gene ,MESH: eIF-2 Kinase/genetics ,Innate immune system ,030102 biochemistry & molecular biology ,MESH: Interferons/pharmacology ,biology.organism_classification ,Virology ,Protein kinase R ,MESH: Cell Line ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,030104 developmental biology ,Poly I-C ,Cell culture ,Vampire bat ,Interferons ,Developmental Biology - Abstract
Bats are known to harbor many zoonotic viruses, some of which are pathogenic to other mammals while they seem to be harmless in bats. As the interferon (IFN) response represents the first line of defense against viral infections in mammals, it is hypothesized that activation of the IFN system is one of the mechanisms enabling bats to co-exist with viruses. We have previously reported induction of type I IFN in a cell line from the common vampire bat, Desmodus rotundus , upon polyinosinic:polycytidylic acid (poly(I:C)) stimulation. To deepen our knowledge on D. rotundus ’ IFN-I antiviral response, we molecularly characterized three interferon-stimulated genes (ISGs), OAS1 , PKR and ADAR1 , closely implicated in the IFN-I antiviral response, and tested their functionality in our cellular model. We first found that D. rotundus encoded two OAS1 paralogs, OAS1a and OAS1b , and that the functional domains of the four ISGs characterized were highly conserved with those of other mammals. Despite their significant transcription level in the absence of stimulation, the transcription of the four ISGs characterized was enhanced by poly(I:C). In addition, the transcription of OAS1a and OAS1b appears to be differentially regulated. These findings demonstrate an active ISG antiviral response in D. rotundus in which OAS1b may play an important role.
- Published
- 2018
39. Development of molecular and cellular tools to decipher the type I IFN pathway of the common vampire bat
- Author
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Eliane F. Meurs, Christine Neuveut, Vincent Lacoste, Laura Chaulet, Marie-Claude Lise, Sarkis Sarkis, Edith Darcissac, Anne Lavergne, Marcel Falk, Stéphanie Dabo, Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hépacivirus et immunité innée, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This study was conducted within the CAROLIA and BATIMMUNE programs. CAROLIA was supported by European funds (ERDF/FEDER) and assistance from the Region Guyane and the Direction Regionale pour la Recherche et la Technologie. BATIMMUNE wasfunded by the Institut Pasteur through a Transversal Research Program (PTR499). This study also received a European Commission 'REGPOT-CT-2011-285837-STRonGer' grant within the FP7 and an 'Investissement d'Avenir ' grant managed by the Agence Nationale de la Recherche (CEBA, Ref. ANR-10-LABEX-25-01)., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,MESH: Signal Transduction ,medicine.disease_cause ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,MESH: DEAD Box Protein 58/genetics ,0302 clinical medicine ,MESH: Lung/immunology ,Chiroptera ,MESH: RNA, Double-Stranded/immunology ,MESH: Animals ,Cloning, Molecular ,Lung ,Cell Line, Transformed ,Innate immunity ,biology ,Toll-Like Receptors ,Pattern recognition receptor ,MESH: Gene Expression Regulation ,3. Good health ,MESH: Toll-Like Receptors/genetics ,RIG-I-Like receptor ,MESH: Chiroptera/genetics ,Host-Pathogen Interactions ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,DEAD Box Protein 58 ,MESH: Immunity, Innate ,Cellular model ,Signal transduction ,Signal Transduction ,030231 tropical medicine ,Immunology ,Computational biology ,Desmodus rotundus ,03 medical and health sciences ,MESH: Rabies virus/physiology ,Toll-like receptor ,MESH: Interferon-alpha/metabolism ,medicine ,Animals ,Humans ,MESH: Poly I-C/immunology ,MESH: Cloning, Molecular ,MESH: Cell Line, Transformed ,Type I interferon ,Disease Reservoirs ,RNA, Double-Stranded ,MESH: Disease Reservoirs ,Innate immune system ,MESH: Humans ,Rabies virus ,MESH: Host-Pathogen Interactions ,MESH: Chiroptera/immunology ,Interferon-alpha ,Interferon-beta ,MESH: Interferon-beta/metabolism ,MESH: Lung/cytology ,biology.organism_classification ,Virology ,Immunity, Innate ,030104 developmental biology ,Poly I-C ,Gene Expression Regulation ,Vampire bat ,TLR3 ,Cell line ,Developmental Biology - Abstract
International audience; Though the common vampire bat, Desmodus rotundus, is known as the main rabies virus reservoir in Latin America, no tools are available to investigate its antiviral innate immune system. To characterize the IFN-I pathway, we established an immortalized cell line from a D. rotundus fetal lung named FLuDero. Then we molecularly characterized some of the Toll-like receptors (TLR3, 7, 8 and 9), the three RIG-I-like receptor members, as well as IFNa1 and IFNb. Challenging the FLuDero cell line with poly (I:C) resulted in an up-regulation of both IFNa1 and IFNb and the induction of expression of the different pattern recognition receptors characterized. These findings provide evidence of the intact dsRNA recognition machinery and the IFN-I signaling pathway in our cellular model. Herein, we generated a sum of insightful specific molecular and cellular tools that will serve as a useful model to study virusehost interactions of the common vampire bat.
- Published
- 2017
40. Development of molecular and cellular tools to decipher the type I IFN pathway of the common vampire bat
- Author
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Sarkis, Sarkis, primary, Lise, Marie-Claude, additional, Darcissac, Edith, additional, Dabo, Stéphanie, additional, Falk, Marcel, additional, Chaulet, Laura, additional, Neuveut, Christine, additional, Meurs, Eliane F., additional, Lavergne, Anne, additional, and Lacoste, Vincent, additional
- Published
- 2018
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41. Increased osteopontin expression in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patient cells is associated with IL-17 expression
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Jean-Michel Mesnard, Raymond Césaire, Antoine Gross, Gildas Belrose, Sarkis Sarkis, Stéphane Olindo, Jean-Marie Peloponese, Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé (CPBS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie-Immunologie [Fort de France, Martinique] (EA 4537), Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Institut de Recherche en Infectiologie de Montpellier (IRIM), Service de neurologie [Fort-de-France, Martinique], and CHU de la Martinique [Fort de France]
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CD4-Positive T-Lymphocytes ,Male ,MESH: Paraparesis, Tropical Spastic ,MESH: Osteopontin ,medicine.medical_treatment ,viruses ,MESH: Interleukin-17 ,Pathogenesis ,Myelopathy ,0302 clinical medicine ,immune system diseases ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,hemic and lymphatic diseases ,Tropical spastic paraparesis ,MESH: Gene Products, tax ,Medicine ,Osteopontin ,Cells, Cultured ,MESH: Aged ,0303 health sciences ,Human T-lymphotropic virus 1 ,MESH: Middle Aged ,biology ,Interleukin-17 ,virus diseases ,MESH: CD4-Positive T-Lymphocytes ,Gene Products, tax ,Middle Aged ,Paraparesis, Tropical Spastic ,3. Good health ,IL-17 ,Infectious Diseases ,Cytokine ,030220 oncology & carcinogenesis ,Carrier State ,Female ,Interleukin 17 ,MESH: Carrier State ,MESH: Cells, Cultured ,MESH: Asymptomatic Diseases ,03 medical and health sciences ,MESH: Gene Expression Profiling ,Virology ,Humans ,030304 developmental biology ,Aged ,MESH: Human T-lymphotropic virus 1 ,MESH: Humans ,business.industry ,Gene Expression Profiling ,medicine.disease ,MESH: Male ,Cell culture ,HTLV-1 ,Immunology ,Asymptomatic Diseases ,biology.protein ,business ,HAM/TSP ,Asymptomatic carrier ,MESH: Female - Abstract
Background HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological inflammatory disease associated with a predominant infiltration of CD4+ T lymphocytes, which are the main subset of HTLV-1-infected cells. It has been demonstrated that in cell line the viral Tax protein transcriptionnally regulate expression of osteopontin, an inflammatory cytokine associated with Th17-related pathologies. Objectives The aim of the study was to explore osteopontin expression in HTLV-1 asymptomatic carriers and in HAM/TSP patients and consequences on IL17 expression. Study design We quantified Tax, osteopontin, RORγ, IL17 and IL22 mRNA expressions in cells from 10 HAM/TSP patients, 6 asymptomatic HTLV-1 carriers (ASY) and 4 HTLV-1-negative healthy donors during ex vivo culture. Results We observed that the expression of osteopontin was higher in HAM/TSP patients and correlated with Tax expression levels. Positive regulation of RORγ, IL17 and IL22 were also observed during cell culture. Conclusions Our results propose a new mechanism which could contribute to HAM/TSP pathogenesis.
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- 2012
42. Increased osteopontin expression in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patient cells is associated with IL-17 expression
- Author
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Sarkis, Sarkis, primary, Belrose, Gildas, additional, Peloponese, Jean-Marie, additional, Olindo, Stéphane, additional, Césaire, Raymond, additional, Mesnard, Jean-Michel, additional, and Gross, Antoine, additional
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- 2013
- Full Text
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43. MOESM1 of p30 protein: a critical regulator of HTLV-1 viral latency and host immunity
- Author
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Moles, Ramona, Sarkis, Sarkis, Galli, Veronica, Omsland, Maria, Purcell, Damian, Yurick, David, Khoury, Georges, Pise-Masison, Cynthia, and Franchini, Genoveffa
- Subjects
viruses ,3. Good health - Abstract
Additional file 1: Figure S1. Amino acid sequence analysis of p30 from HTLV-1A infected individuals. Alignment of p30 amino acid sequences of from 160 HTLV-1A patients was used to generate a consensus. Dashes (–) indicate gaps in the amino acid alignment, asterisks (*) represent stop codons, and periods (.) represent similarity. The multi-alignment was performed with the Mega7 program using default parameters.
44. MOESM1 of p30 protein: a critical regulator of HTLV-1 viral latency and host immunity
- Author
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Moles, Ramona, Sarkis, Sarkis, Galli, Veronica, Omsland, Maria, Purcell, Damian, Yurick, David, Khoury, Georges, Pise-Masison, Cynthia, and Franchini, Genoveffa
- Subjects
viruses ,3. Good health - Abstract
Additional file 1: Figure S1. Amino acid sequence analysis of p30 from HTLV-1A infected individuals. Alignment of p30 amino acid sequences of from 160 HTLV-1A patients was used to generate a consensus. Dashes (–) indicate gaps in the amino acid alignment, asterisks (*) represent stop codons, and periods (.) represent similarity. The multi-alignment was performed with the Mega7 program using default parameters.
45. Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIV mac251 acquisition in macaques.
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Rahman MA, Becerra-Flores M, Patskovsky Y, Silva de Castro I, Bissa M, Basu S, Shen X, Williams LD, Sarkis S, N'guessan KF, LaBranche C, Tomaras GD, Aye PP, Veazey R, Paquin-Proulx D, Rao M, Franchini G, and Cardozo T
- Subjects
- Animals, Cholera Toxin, Epitopes, Macaca mulatta, AIDS Vaccines, HIV Infections prevention & control
- Abstract
Introduction: An efficacious HIV vaccine will need to elicit a complex package of innate, humoral, and cellular immune responses. This complex package of responses to vaccine candidates has been studied and yielded important results, yet it has been a recurring challenge to determine the magnitude and protective effect of specific in vivo immune responses in isolation. We therefore designed a single, viral-spike-apical, epitope-focused V2 loop immunogen to reveal individual vaccine-elicited immune factors that contribute to protection against HIV/SIV., Method: We generated a novel vaccine by incorporating the V2 loop B-cell epitope in the cholera toxin B (CTB) scaffold and compared two new immunization regimens to a historically protective 'standard' vaccine regimen (SVR) consisting of 2xDNA prime boosted with 2xALVAC-SIV and 1xΔV1gp120. We immunized a cohort of macaques with 5xCTB-V2c vaccine+alum intramuscularly simultaneously with topical intrarectal vaccination of CTB-V2c vaccine without alum (5xCTB-V2/alum). In a second group, we tested a modified version of the SVR consisting of 2xDNA prime and boosted with 1xALVAC-SIV and 2xALVAC-SIV+CTB-V2/alum, (DA/CTB-V2c/alum)., Results: In the absence of any other anti-viral antibodies, V2c epitope was highly immunogenic when incorporated in the CTB scaffold and generated highly functional anti-V2c antibodies in the vaccinated animals. 5xCTB-V2c/alum vaccination mediated non-neutralizing ADCC activity and efferocytosis, but produced low avidity, trogocytosis, and no neutralization of tier 1 virus. Furthermore, DA/CTB-V2c/alum vaccination also generated lower total ADCC activity, avidity, and neutralization compared to the SVR. These data suggest that the ΔV1gp120 boost in the SVR yielded more favorable immune responses than its CTB-V2c counterpart. Vaccination with the SVR generates CCR5
- α4β7+ CD4+ Th1, Th2, and Th17 cells, which are less likely to be infected by SIV/HIV and likely contributed to the protection afforded in this regimen. The 5xCTB-V2c/alum regimen likewise elicited higher circulating CCR5- α4β7+ CD4+ T cells and mucosal α4β7+ CD4+ T cells compared to the DA/CTB-V2c/alum regimen, whereas the first cell type was associated with reduced risk of viral acquisition., Conclusion: Taken together, these data suggest that individual viral spike B-cell epitopes can be highly immunogenic and functional as isolated immunogens, although they might not be sufficient on their own to provide full protection against HIV/SIV infection., Competing Interests: Authors SB, KN’G, and DP-P were employed by Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. Patent applications have been filed with the US Patent and Trademark Office on the use of CTB-V2 immunogens for an HIV vaccine, naming TC and GF as inventors. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rahman, Becerra-Flores, Patskovsky, Silva de Castro, Bissa, Basu, Shen, Williams, Sarkis, N’guessan, LaBranche, Tomaras, Aye, Veazey, Paquin-Proulx, Rao, Franchini and Cardozo.)- Published
- 2023
- Full Text
- View/download PDF
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