Selected Grantee Publications
- Clear All
- 247 results found
- HIV/AIDS
- Neurological
Myelin‐Specific T Cells in Animals With Japanese Macaque Encephalomyelitis
Govindan et al., Annals of Clinical and Translational Neurology. 2021.
https://onlinelibrary.wiley.com/doi/10.1002/acn3.51303
Investigators characterized the CD4+ and CD8+ T cells in demyelinating Japanese macaque encephalomyelitis (JME) lesions in age‐ and sex‐matched macaques and discovered differences in expression of myelin antigen sequences in the T cell. Mapping myelin epitopes revealed a heterogeneity in T cell responses among JME animals, which are associated with a proinflammatory pathogenic role in multiple sclerosis (MS). These findings draw further parallels between JME and MS and support the hypothesis that JME and possibly MS are triggered by mechanisms involving myelin damage and not myelin epitope mimicry. Supported by ORIP (P51OD011092) and NINDS.
Thresholds for Post-Rebound SHIV Control after CCR5 Gene-Edited Autologous Hematopoietic Cell Transplantation
Cardozo-Ojeda et al., eLife. 2021.
https://elifesciences.org/articles/57646
Investigators developed a mathematical model to project the minimum threshold of C-C chemokine receptor type 5 (CCR5) gene-edited cells necessary for a functional cure from HIV. This was based on blood T cell reconstitution and plasma simian-HIV (SHIV) dynamics from SHIV-1157ipd3N4-infected juvenile pig-tailed macaques that underwent autologous transplantation with CCR5 gene editing. The model predicts that viral control can be obtained following analytical treatment interruption (ATI) when: (1) transplanted hematopoietic stem and progenitor cells (HSPCs) are at least fivefold higher than residual endogenous HSPCs after total body irradiation and (2) the fraction of protected HSPCs in the transplant achieves a threshold (76–94%) sufficient to overcome transplantation-dependent loss of SHIV immunity. Under these conditions, if ATI is withheld until transplanted gene-modified cells engraft and reconstitute to a steady state, spontaneous viral control is projected to occur. Supported by ORIP (P51OD010425), NCATS and NIAID.
Increased Proviral DNA in Circulating Cells Correlates With Plasma Viral Rebound in SIV-Infected Rhesus Macaques after Antiretroviral Therapy Interruption
Ziani et al., Journal of Virology. 2021.
https://jvi.asm.org/content/early/2021/01/05/JVI.02064-20
Investigators longitudinally tracked dynamic decay of cell-associated viral RNA/DNA in systemic and lymphoid tissues in SIV-infected rhesus macaques on prolonged combined antiretroviral therapy (cART) to evaluate predictors of viral rebound after treatment cessation. Suppressive cART substantially reduced plasma SIV RNA, cell-associated unspliced, and multiply spliced SIV RNA to undetectable levels, yet viral DNA remained detectable in systemic tissues and lymphoid compartments throughout cART. A rapid increase of integrated proviral DNA in peripheral mononuclear cells was detected once cART was withdrawn, accompanied by the emergence of detectable plasma viral load. The increase of peripheral proviral DNA post cART interruption correlated with the emergence and degree of viral rebound. These results suggest that measuring total viral DNA in SIV infection may be a relatively simple surrogate marker of reservoir size, and may predict viral rebound after treatment interruption, and inform treatment strategies. Supported by ORIP (P51OD011104), NIAID and NICHD.
Antibody-Mediated Depletion of Viral Reservoirs is Limited in SIV-Infected Macaques Treated Early With Antiretroviral Therapy
Swanstrom et al., Journal of Clinical Investigation. 2021.
https://doi.org/10.1172/JCI142421
Virus-specific strategies to target the latent HIV reservoir in individuals on combination antiretroviral therapy (cART) have been limited by inefficient induction of viral protein expression. Researchers used rhesus macaques to investigate an antibody-mediated reservoir targeting strategy, targeting the CD4 molecule rather than a viral protein, to deplete potential viral target cells irrespective of infection status. Despite profound CD4+ T cell depletion in blood and lymph nodes, time to viral rebound following cART cessation was not delayed in anti-CD4 treated animals compared with controls, likely due to the limited antibody-mediated cell depletion that occurred in rectal tissue and lymphoid follicles. Supported by ORIP (R24OD010976), NCI, and NIAID.
Infant Isoflurane Exposure Affects Social Behaviours, but Does Not Impair Specific Cognitive Domains in Juvenile Non-Human Primates
Neudecker et al., British Journal of Anaesthesia. 2020.
https://www.sciencedirect.com/science/article/pii/S0007091220308503
Researchers investigated the impact of extended (5 hours) isoflurane anesthetic exposure (1-3 exposures) of rhesus macaque (RM) infants of both sexes on cognitive testing and behavioral assessments. Cognitive function did not differ among groups; however, compared to controls, RMs exposed three times during infancy exhibited less close social behavior. One isoflurane exposure resulted in increased anxiety-related behaviors and more inhibition towards novel objects. These findings are consistent with behavioral alterations observed in social settings of human clinical studies. Supported by ORIP (P51OD011092).
Lipocalin-2 Is an Anorexigenic Signal in Primates
Petropoulou et al., eLife. 2020.
https://doi.org/10.7554/eLife.58949
The hormone lipocalin-2 (LCN2) suppresses food intake in mice. Researchers demonstrated that LCN2 increases after a meal and reduces hunger in people with normal weight or overweight, but not in obese individuals. The researchers also showed that LCN2 crosses the blood-brain barrier and binds to the hypothalamus in vervet monkeys. LCN2 was found to bind to the hypothalamus in human, baboon, and rhesus macaque brain sections. When injected into vervets, LCN2 suppressed food intake and lowered body weight without toxic effects in short-term experiments. These findings lay the groundwork to investigate whether LCN2 might be a useful treatment for obesity. Supported by ORIP (P40OD010965), NCATS, NIDDK, NIA, and NHLBI.
Antiretroviral Therapy Does Not Reduce Tuberculosis Reactivation in a Tuberculosis-HIV Coinfection Model
Ganatra et al., Journal of Clinical Investigation. 2020.
https://www.jci.org/articles/view/136502
Despite treatment of HIV with antiretroviral therapy (ART), the risk of tuberculosis (TB) reactivation is higher in HIV-infected than HIV-uninfected persons. Researchers used Mycobacterium tuberculosis/SIV-coinfected rhesus macaques to model the impact of ART on TB reactivation due to HIV-induced immunosuppression. ART significantly reduced viral loads and increased CD4+ T-cell counts in blood, spleen, and bronchoalveolar lavage samples, but it did not reduce the risk of SIV-induced TB reactivation during the early phase of treatment. This study offers a translational model for the investigation of TB/SIV coinfection and the evaluation of treatment regimens to prevent TB reactivation in HIV-infected individuals. Supported by ORIP (P51OD011133, P51OD011132) and NIAID.