Selected Grantee Publications
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- 281 results found
- Aquatic Vertebrate Models
- Nonhuman Primate Models
Assessment of Anti-CD20 Antibody Pre-Treatment for Augmentation of CAR-T Cell Therapy in SIV-Infected Rhesus Macaques
Pampusch et al., Frontiers in Immunology. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9941136/
Chronic HIV replication occurs primarily within lymphoid follicles, and investigators hypothesized that temporary disruption of these follicles would create space for chimeric antigen receptor (CAR) T cell engraftment and lead to increased abundance and persistence of CAR T cells. They evaluated CAR T cell abundance and persistence in rhesus macaques of both sexes following simian immunodeficiency virus (SIV) infection and antiretroviral therapy suppression. Their results suggest that CAR T cells expanded to a greater extent in the depleted and CAR T cell–treated animals. Further studies are needed to evaluate strategies for engraftment and the persistence of HIV-specific CAR T cells. Supported by ORIP (P51OD011106, P51RR000167), NIAID, and NIDA.
SIV Infection Regulates Compartmentalization of Circulating Blood Plasma miRNAs within Extracellular Vesicles (EVs) and Extracellular Condensates (ECs) and Decreases EV-Associated miRNA-128
Kopcho et al., Viruses. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059597/
MicroRNAs (miRNAs) are thought to be involved in HIV pathogenesis, but the effect of HIV on the compartmentalization of miRNAs within extracellular particles is unclear. Researchers sequenced the small RNA population of paired EVs and ECs from male rhesus macaques. They showed that extracellular miRNAs in blood plasma are not restricted to any type of extracellular particles but are associated with lipid‑based carriers, with a significant proportion associated with ECs. Further, simian immunodeficiency virus (SIV) infection altered the miRNAome profile of EVs and revealed miR‑128‑3p as a potential target of infection. This work suggests that EV‑ and EC‑associated miRNAs potentially could serve as biomarkers for various diseases. Supported by ORIP (P51OD011104, P51OD011133), NIAID, and NIDA.
Prolonged Experimental CD4+ T-Cell Depletion Does Not Cause Disease Progression In SIV-Infected African Green Monkeys
Le Hingrat et al., Nature Communications. 2023.
https://www.nature.com/articles/s41467-023-36379-2
Chronically simian immunodeficiency virus (SIV)–infected African green monkeys (AGMs) partially recover mucosal CD4+ T cells, maintain gut integrity, and do not progress to AIDS. Investigators assessed the impact of prolonged, antibody-mediated CD4+ T cell depletion on gut integrity and natural history of SIV infection in AGMs. All circulating CD4+ T cells and more than 90% of mucosal CD4+ T cells were depleted. Plasma viral loads and cell-associated viral RNA in tissues were lower in CD4+-cell-depleted animals. CD4+-cell-depleted AGMs maintained gut integrity, controlled immune activation, and did not progress to AIDS. Therefore, CD4+ T cell depletion is not a determinant of SIV-related gut dysfunction when gastrointestinal tract epithelial damage and inflammation are absent, suggesting that disease progression and resistance to AIDS are independent of CD4+ T cell restoration in SIV-infected AGMs. Supported by ORIP (P40OD028116), NIAID, NIDDK, and NHLBI.
Genome Structures Resolve the Early Diversification of Teleost Fishes
Parey et al., Science. 2023.
https://pubmed.ncbi.nlm.nih.gov/36758078/
The early evolution of teleost fishes remains an unanswered question among evolutionary biologists. The three earliest branching clades of crown teleosts are Elopomorpha (e.g., tarpons, eels), Osteoglossomorpha (e.g., arapaima, elephantnose fish), and Clupeocephala (e.g., zebrafish, medaka). Building on recently described genome assemblies in Elopomorpha, the authors explored teleost phylogeny using independent gene sequencing and chromosomal rearrangement phylogenomic approaches. They found that Elopomorpha and Osteoglossomorpha comprise a monophyletic sister group to all other teleosts. This report highlights the value of combining different levels of genome-wide information to solve complex phylogenies and will serve as a basis for new investigations into the genomic and functional evolution of teleosts. Supported by ORIP (R01OD011116).
Alterations in Abundance and Compartmentalization of miRNAs in Blood Plasma Extracellular Vesicles and Extracellular Condensates during HIV/SIV Infection and its Modulation by Antiretroviral Therapy (ART) and Delta-9-Tetrahydrocannabinol (Δ9-THC)
Kopcho et al., Viruses. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053514/
MicroRNAs (miRNAs) have been shown to regulate host response to HIV infection. Previously, investigators proposed that the assortment of extracellular miRNAs into distinct carriers could provide a new dimension to miRNA-based biomarkers. In this follow-up study, the investigators used particle purification liquid chromatography to determine the abundance and compartmentalization of blood plasma extracellular miRNAs into extracellular vesicles and extracellular condensates during simian immunodeficiency virus (SIV) infection in male rhesus macaques. They reported that different treatments—combination ART and Δ9‑THC—impart distinct effects on the enrichment and compartmentalization of extracellular miRNAs. These data suggest that the extracellular miRNA profile in blood plasma is altered following SIV infection. Supported by ORIP (P51OD011104, P51OD011133), NIAID, and NIDA.
CD8+ Lymphocytes Do Not Impact SIV Reservoir Establishment under ART
Statzu et al., Nature Microbiology. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894752/
The HIV-1 latent reservoir has been shown to persist following antiretroviral therapy (ART), but the mechanisms underlying the establishment and maintenance of the reservoir are not fully understood. Using rhesus macaques of both sexes, investigators examined the effects of CD8+ T cells on formation of the latent reservoir with simian immunodeficiency virus (SIV) infection. They found that CD8+ T cell depletion resulted in slower decline of viremia but did not change the frequency of infected CD4+ T cells in the blood or lymph nodes. Additionally, the size of the persistent reservoir was unchanged. These findings suggest that the viral reservoir is established largely independent of SIV-specific cytotoxic T lymphocyte control. Supported by ORIP (P51OD011132), NIAID, NCI, NIDDK, NIDA, NHLBI, and NINDS.
Production and Characterization of Monoclonal Antibodies to Xenopus Proteins
Horr et al., Development. 2023.
https://pubmed.ncbi.nlm.nih.gov/36789951/
Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identification of subcellular localization and characterization of the function of target proteins of interest. However, because there can be considerable sequence diversity between orthologous proteins in Xenopus and mammals, antibodies produced against mouse or human proteins often do not recognize Xenopus counterparts. To address this issue, the authors refined existing mouse monoclonal antibody production protocols to generate antibodies against Xenopus proteins of interest. Here, they describe several approaches for the generation of useful mouse anti-Xenopus antibodies to multiple Xenopus proteins and their validation in various experimental approaches. Supported by ORIP (R24OD021485, S10OD010645) and NIDCR.
Impaired Placental Hemodynamics and Function in a Non-Human Primate Model of Gestational Protein Restriction
Lo et al., Scientific Reports. 2023.
https://www.nature.com/articles/s41598-023-28051-y
Maternal malnutrition is a global health epidemic that adversely affects fetal outcomes and results in long-term health complications in children. Investigators used a previously developed model in nonhuman primates for gestational protein restriction to study the impact of undernutrition, specifically protein deficiency, on placental function and pregnancy outcomes. The data demonstrate that a 50% protein-restricted diet reduces maternal placental perfusion, decreases fetal oxygen availability, and increases fetal mortality. These alterations in placental hemodynamics could partly explain human growth restriction and stillbirth seen with severe protein restriction in developing countries. Supported by ORIP (P51OD011092) and NICHD.
Duration of Antiretroviral Therapy Impacts the Degree of Residual SIV Infection in the Gut in Long‐Term Non‐Progressing Chinese Rhesus Macaques
Solis-Leal et al., Journal of Medical Virology. 2023.
https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.28185
HIV and simian immunodeficiency virus (SIV) reservoirs have been shown to persist with antiretroviral therapy (ART), particularly in the gut‐associated lymphoid tissues in the intestine. The effects of ART on the reservoir size, however, had not been explored fully. In this study, researchers used male Chinese‐origin rhesus macaques to assess the effects of long- and short-term ART on gut infection—across segments of the small and large intestines—in long‐term non‐progressors (LTNPs). They reported that although ART does not eliminate SIV in LTNPs, a longer ART period dramatically reduces SIV infection and diversity in the gut. Further studies are needed to better understand the reduction of HIV gut reservoirs in this context. Supported by ORIP (P51OD011133, P51OD011104), NIAID, NIMH, and NINDS.
Gigapixel Imaging With a Novel Multi-Camera Array Microscope
Thomson et al., eLife. 2022.
https://www.doi.org/10.7554/eLife.74988
The dynamics of living organisms are organized across many spatial scales. The investigators created assembled a scalable multi-camera array microscope (MCAM) that enables comprehensive high-resolution, large field-of-view recording from multiple spatial scales simultaneously, ranging from structures that approach the cellular scale to large-group behavioral dynamics. By collecting data from up to 96 cameras, they computationally generated gigapixel-scale images and movies with a field of view over hundreds of square centimeters at an optical resolution of 18 µm. This system allows the team to observe the behavior and fine anatomical features of numerous freely moving model organisms on multiple spatial scales (e.g., larval zebrafish, fruit flies, slime mold). Overall, by removing the bottlenecks imposed by single-camera image acquisition systems, the MCAM provides a powerful platform for investigating detailed biological features and behavioral processes of small model organisms. Supported by ORIP (R44OD024879), NIEHS, NCI, and NIBIB.