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1.
PLoS Pathog ; 16(12): e1009055, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33270809

RESUMO

To counter HIV latency, it is important to develop a better understanding of the full range of host factors promoting latency. Their identification could suggest new strategies to reactivate latent proviruses and subsequently kill the host cells ("shock and kill"), or to permanently silence these latent proviruses ("block and lock"). We recently developed a screening strategy termed "Reiterative Enrichment and Authentication of CRISPRi Targets" (REACT) that can unambiguously identify host genes promoting HIV latency, even in the presence of high background "noise" produced by the stochastic nature of HIV reactivation. After applying this strategy in four cell lines displaying different levels of HIV inducibility, we identified FTSJ3, TMEM178A, NICN1 and the Integrator Complex as host genes promoting HIV latency. shRNA knockdown of these four repressive factors significantly enhances HIV expression in primary CD4 T cells, and active HIV infection is preferentially found in cells expressing lower levels of these four factors. Mechanistically, we found that downregulation of these newly identified host inhibitors stimulates different stages of RNA Polymerase II-mediated transcription of HIV-1. The identification and validation of these new host inhibitors provide insight into the novel mechanisms that maintain HIV latency even when cells are activated and undergo cell division.


Assuntos
Infecções por HIV/metabolismo , HIV-1/metabolismo , Latência Viral/fisiologia , Linfócitos T CD4-Positivos/virologia , Regulação Viral da Expressão Gênica , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Soropositividade para HIV/genética , Soropositividade para HIV/imunologia , HIV-1/patogenicidade , HIV-1/fisiologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Células Jurkat , Provírus/genética , Ativação Viral/genética
2.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-36824381

RESUMO

Tadpoles display preferences for different environments but the sensory modalities that govern these choices are not well understood. Here, we examined light preferences and associated sensory mechanisms of albino and wild-type Xenopus laevis tadpoles. We found that albino tadpoles spent more time in darker environments compared to the wild type, although they showed no differences in overall activity. This preference persisted when the tadpoles had their optic nerve severed or pineal glands removed, suggesting these sensory systems alone are not necessary for phototaxis. These experiments were conducted by an undergraduate laboratory course, highlighting how X. laevis tadpole behavior assays in a classroom setting can reveal new insights into animal behavior.

3.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37008729

RESUMO

Many ant species are equipped with chemical defenses, although how these compounds impact nervous system function is unclear. Here, we examined the utility of Caenorhabditis elegans chemotaxis assays for investigating how ant chemical defense compounds are detected by heterospecific nervous systems. We found that C. elegans respond to extracts from the invasive Argentine Ant ( Linepithema humile ) and the osm-9 ion channel is required for this response. Divergent strains varied in their response to L. humile extracts, suggesting genetic variation underlying chemotactic responses. These experiments were conducted by an undergraduate laboratory course, highlighting how C. elegans chemotaxis assays in a classroom setting can provide genuine research experiences and reveal new insights into interspecies interactions.

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