11 results on '"Raehtz, Kevin D."'
Search Results
2. Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection.
- Author
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Symmonds, Jen, Gaufin, Thaidra, Xu, Cuiling, Raehtz, Kevin D., Ribeiro, Ruy M., Pandrea, Ivona, and Apetrei, Cristian
- Subjects
SIMIAN immunodeficiency virus ,HIV ,HIV infections ,CELL populations ,AIDS vaccines ,KILLER cells - Abstract
Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus's direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. High-fat diet exacerbates SIV pathogenesis and accelerates disease progression
- Author
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He, Tianyu, Xu, Cuiling, Krampe, Noah, Dillon, Stephanie M., Sette, Paola, Falwell, Elizabeth, Haret-Richter, George S., Butterfield, Tiffany, Dunsmore, Tammy L., McFadden, William M., Jr., Martin, Kathryn J., Policicchio, Benjamin B., Raehtz, Kevin D., Penn, Ellen P., Tracy, Russell P., Ribeiro, Ruy M., Frank, Daniel N., Wilson, Cara C., Landay, Alan L., Apetrei, Cristian, and Pandrea, Ivona
- Subjects
Obesity -- Development and progression -- Risk factors -- Physiological aspects -- Health aspects ,HIV infections -- Development and progression -- Risk factors -- Physiological aspects -- Health aspects ,Diseases -- Development and progression -- Risk factors -- Physiological aspects -- Health aspects ,Liver diseases -- Development and progression -- Risk factors -- Physiological aspects -- Health aspects ,Type 2 diabetes -- Development and progression -- Risk factors -- Physiological aspects -- Health aspects ,Cholesterol -- Physiological aspects -- Health aspects ,Comorbidity -- Development and progression -- Risk factors -- Physiological aspects -- Health aspects ,Liver -- Physiological aspects -- Health aspects ,Simian immunodeficiency virus -- Development and progression -- Risk factors -- Physiological aspects -- Health aspects ,Diet -- Physiological aspects -- Health aspects ,Primates ,HIV ,Adipose tissue ,Inflammation ,DNA ,Atherosclerosis ,HIV patients ,Fibrosis ,Oxidation-reduction reactions ,Infection ,RNA ,Communicable diseases ,Health care industry - Abstract
Consuming a high-fat diet (HFD) is a risk factor for obesity and diabetes; both of these diseases are also associated with systemic inflammation, similar to HIV infection. A HFD induces intestinal dysbiosis and impairs liver function and coagulation, with a potential negative impact on HIV/SIV pathogenesis. We administered a HFD rich in saturated fats and cholesterol to nonpathogenic (African green monkeys) and pathogenic (pigtailed macaques) SIV hosts. The HFD had a negative impact on SIV disease progression in both species. Thus, increased cell-associated SIV DNA and RNA occurred in the HFD-receiving nonhuman primates, indicating a potential reservoir expansion. The HFD induced prominent immune cell infiltration in the adipose tissue, an important SIV reservoir, and heightened systemic immune activation and inflammation, altering the intestinal immune environment and triggering gut damage and microbial translocation. Furthermore, HFD altered lipid metabolism and HDL oxidation and also induced liver steatosis and fibrosis. These metabolic disturbances triggered incipient atherosclerosis and heightened cardiovascular risk in the SIV-infected HFD-receiving nonhuman primates. Our study demonstrates that dietary intake has a discernable impact on the natural history of HIV/SIV infections and suggests that dietary changes can be used as adjuvant approaches for HIV-infected subjects, to reduce inflammation and the risk of non-AIDS comorbidities and possibly other infectious diseases., Introduction Persistent immune activation and inflammation are hallmarks of chronic HIV/SIV infection and strong predictors of disease progression, independent of plasma viral loads (pVLs), or peripheral [CD4.sup.+] T cell counts [...]
- Published
- 2019
- Full Text
- View/download PDF
4. T cell activation is insufficient to drive SIV disease progression
- Author
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Apetrei, Cristian, primary, Gaufin, Thaidra, additional, Brocca-Cofano, Egidio, additional, Sivanandham, Ranjit, additional, Sette, Paola, additional, He, Tianyu, additional, Sivanandham, Sindhuja, additional, Martinez Sosa, Natalie, additional, Martin, Kathryn J., additional, Raehtz, Kevin D., additional, Kleinman, Adam J., additional, Valentine, Audrey, additional, Krampe, Noah, additional, Gautam, Rajeev, additional, Lackner, Andrew A., additional, Landay, Alan L., additional, Ribeiro, Ruy M., additional, and Pandrea, Ivona, additional
- Published
- 2023
- Full Text
- View/download PDF
5. CD8+ T cells control SIV infection using both cytolytic effects and non-cytolytic suppression of virus production.
- Author
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Policicchio, Benjamin B., Cardozo-Ojeda, Erwing Fabian, Xu, Cuiling, Ma, Dongzhu, He, Tianyu, Raehtz, Kevin D., Sivanandham, Ranjit, Kleinman, Adam J., Perelson, Alan S., Apetrei, Cristian, Pandrea, Ivona, and Ribeiro, Ruy M.
- Subjects
HIV infections ,T cells ,INFECTION control ,RHESUS monkeys ,VIRAL load ,INTEGRASE inhibitors - Abstract
Whether CD8
+ T lymphocytes control human immunodeficiency virus infection by cytopathic or non-cytopathic mechanisms is not fully understood. Multiple studies highlighted non-cytopathic effects, but one hypothesis is that cytopathic effects of CD8+ T cells occur before viral production. Here, to examine the role of CD8+ T cells prior to virus production, we treated SIVmac251-infected macaques with an integrase inhibitor combined with a CD8-depleting antibody, or with either reagent alone. We analyzed the ensuing viral dynamics using a mathematical model that included infected cells pre- and post- viral DNA integration to compare different immune effector mechanisms. Macaques receiving the integrase inhibitor alone experienced greater viral load decays, reaching lower nadirs on treatment, than those treated also with the CD8- depleting antibody. Models including CD8+ cell-mediated reduction of viral production (non-cytolytic) were found to best explain the viral profiles across all macaques, in addition an effect in killing infected cells pre-integration (cytolytic) was supported in some of the best models. Our results suggest that CD8+ T cells have both a cytolytic effect on infected cells before viral integration, and a direct, non-cytolytic effect by suppressing viral production. Control of HIV and SIV infection is largely thought to be achieved through direct lysis of target cells. Here, using mathematical modelling of viral load data from rhesus macaques, the authors propose that virus control is best explained by the combination of cytolytic and non-cytolytic effects. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
6. African green monkeys avoid SIV disease progression by preventing intestinal dysfunction and maintaining mucosal barrier integrity
- Author
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Raehtz, Kevin D., Barrenäs, Fredrik, Xu, Cuiling, Busman-Sahay, Kathleen, Valentine, Audrey, Law, Lynn, Ma, Dongzhu, Policicchio, Benjamin B., Wijewardana, Viskam, Brocca-Cofano, Egidio, Trichel, Anita, Gale, Michael, Jr., Keele, Brandon F., Estes, Jacob D., Apetrei, Cristian, Pandrea, Ivona, Raehtz, Kevin D., Barrenäs, Fredrik, Xu, Cuiling, Busman-Sahay, Kathleen, Valentine, Audrey, Law, Lynn, Ma, Dongzhu, Policicchio, Benjamin B., Wijewardana, Viskam, Brocca-Cofano, Egidio, Trichel, Anita, Gale, Michael, Jr., Keele, Brandon F., Estes, Jacob D., Apetrei, Cristian, and Pandrea, Ivona
- Abstract
African nonhuman primates that are natural hosts to SIVs can provide us with unique insight into the pathogenesis of HIV disease due to their remarkable ability to avoid progression to AIDS, despite high levels of viral replication. A key question of SIV pathogenesis in natural hosts is whether the lack of disease progression is due to an exquisite ability to repair lesions occurring during the acute infection or to completely maintain the integrity of the mucosal barrier throughout the SIV infection. In pathogenic HIV/SIV infections of humans and macaques, the mucosal integrity is compromised during acute infection, leading to leakage of gut microbial byproducts and to the occurrence of chronic local and systemic inflammation, which plays a crucial role in driving progression to AIDS. Our study shows that the mucosal barrier integrity is never lost in African green monkeys, thereby avoiding the effects of chronic inflammation and disease progression. Unlike HIV infection, SIV infection is generally nonpathogenic in natural hosts, such as African green monkeys (AGMs), despite life-long high viral replication. Lack of disease progression was reportedly based on the ability of SIV-infected AGMs to prevent gut dysfunction, avoiding microbial translocation and the associated systemic immune activation and chronic inflammation. Yet, the maintenance of gut integrity has never been documented, and the mechanism(s) by which gut integrity is preserved are unknown. We sought to investigate the early events of SIV infection in AGMs, specifically examining the impact of SIVsab infection on the gut mucosa. Twenty-nine adult male AGMs were intrarectally infected with SIVsab92018 and serially sacrificed at well-defined stages of SIV infection, preramp-up (1-3 days post-infection (dpi)), ramp-up (4-6 dpi), peak viremia (9-12 dpi), and early chronic SIV infection (46-55 dpi), to assess the levels of immune activation, apoptosis, epithelial damage and microbial translocation in the G
- Published
- 2020
- Full Text
- View/download PDF
7. African green monkeys avoid SIV disease progression by preventing intestinal dysfunction and maintaining mucosal barrier integrity
- Author
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Raehtz, Kevin D., primary, Barrenäs, Fredrik, additional, Xu, Cuiling, additional, Busman-Sahay, Kathleen, additional, Valentine, Audrey, additional, Law, Lynn, additional, Ma, Dongzhu, additional, Policicchio, Benjamin B., additional, Wijewardana, Viskam, additional, Brocca-Cofano, Egidio, additional, Trichel, Anita, additional, Gale, Michael, additional, Keele, Brandon F., additional, Estes, Jacob D., additional, Apetrei, Cristian, additional, and Pandrea, Ivona, additional
- Published
- 2020
- Full Text
- View/download PDF
8. Marginal Effects of Systemic CCR5 Blockade with Maraviroc on Oral Simian Immunodeficiency Virus Transmission to Infant Macaques
- Author
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Brocca-Cofano, Egidio, primary, Xu, Cuiling, additional, Wetzel, Katherine S., additional, Cottrell, Mackenzie L., additional, Policicchio, Benjamin B., additional, Raehtz, Kevin D., additional, Ma, Dongzhu, additional, Dunsmore, Tammy, additional, Haret-Richter, George S., additional, Musaitif, Karam, additional, Keele, Brandon F., additional, Kashuba, Angela D., additional, Collman, Ronald G., additional, Pandrea, Ivona, additional, and Apetrei, Cristian, additional
- Published
- 2018
- Full Text
- View/download PDF
9. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers
- Author
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Policicchio, Benjamin B., primary, Xu, Cuiling, additional, Brocca-Cofano, Egidio, additional, Raehtz, Kevin D., additional, He, Tianyu, additional, Ma, Dongzhu, additional, Li, Hui, additional, Sivanandham, Ranjit, additional, Haret-Richter, George S., additional, Dunsmore, Tammy, additional, Trichel, Anita, additional, Mellors, John W., additional, Hahn, Beatrice H., additional, Shaw, George M., additional, Ribeiro, Ruy M., additional, Pandrea, Ivona, additional, and Apetrei, Cristian, additional
- Published
- 2016
- Full Text
- View/download PDF
10. Critical Role for the Adenosine Pathway in Controlling Simian Immunodeficiency Virus-Related Immune Activation and Inflammation in Gut Mucosal Tissues
- Author
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He, Tianyu, primary, Brocca-Cofano, Egidio, additional, Gillespie, Delbert G., additional, Xu, Cuiling, additional, Stock, Jennifer L., additional, Ma, Dongzhu, additional, Policicchio, Benjamin B., additional, Raehtz, Kevin D., additional, Rinaldo, Charles R., additional, Apetrei, Cristian, additional, Jackson, Edwin K., additional, Macatangay, Bernard J. C., additional, and Pandrea, Ivona, additional
- Published
- 2015
- Full Text
- View/download PDF
11. High-fat diet exacerbates SIV pathogenesis and accelerates disease progression.
- Author
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Tianyu He, Cuiling Xu, Krampe, Noah, Dillon, Stephanie M., Sette, Paola, Falwell, Elizabeth, Haret-Richter, George S., Butterfield, Tiffany, Dunsmore, Tammy L., McFadden Jr., William M., Martin, Kathryn J., Policicchio, Benjamin B., Raehtz, Kevin D., Penn, Ellen P., Tracy, Russell P., Ribeiro, Ruy M., Frank, Daniel N., Wilson, Cara C., Landay, Alan L., and Apetrei, Cristian
- Subjects
- *
PATHOLOGY , *HIGH-fat diet , *DISEASE progression , *CERCOPITHECUS aethiops , *HIV infections , *CARRIER state (Communicable diseases) , *ADIPOSE tissue diseases - Abstract
Consuming a high-fat diet (HFD) is a risk factor for obesity and diabetes; both of these diseases are also associated with systemic inflammation, similar to HIV infection. A HFD induces intestinal dysbiosis and impairs liver function and coagulation, with a potential negative impact on HIV/SIV pathogenesis. We administered a HFD rich in saturated fats and cholesterol to nonpathogenic (African green monkeys) and pathogenic (pigtailed macaques) SIV hosts. The HFD had a negative impact on SIV disease progression in both species. Thus, increased cell-associated SIV DNA and RNA occurred in the HFD-receiving nonhuman primates, indicating a potential reservoir expansion. The HFD induced prominent immune cell infiltration in the adipose tissue, an important SIV reservoir, and heightened systemic immune activation and inflammation, altering the intestinal immune environment and triggering gut damage and microbial translocation. Furthermore, HFD altered lipid metabolism and HDL oxidation and also induced liver steatosis and fibrosis. These metabolic disturbances triggered incipient atherosclerosis and heightened cardiovascular risk in the SIV-infected HFD-receiving nonhuman primates. Our study demonstrates that dietary intake has a discernable impact on the natural history of HIV/SIV infections and suggests that dietary changes can be used as adjuvant approaches for HIV-infected subjects, to reduce inflammation and the risk of non-AIDS comorbidities and possibly other infectious diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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