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1.
J Med Virol ; 93(4): 1923-1925, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33386773

RESUMO

SARS-CoV-2 nucleocapsid (N) protein has been proposed as a good vaccine target. N-specific T cells were observed in SARS-CoV-2 N immunized mice and COVID-19 convalescents. It is of importance to identify the T cell responses triggered by SARS-CoV-2 N protein. Intradermal immunization with SARS-CoV N protein was demonstrated to elicit non-protective T cell responses which may be avoided by intranasal vaccination. Therefore, we conducted intranasal vaccination of BALB/c mice with recombinant adenovirus type-5 expressing SARS-CoV-2 N protein. Such procedure induced CD8 T cell responses in the lung. Meanwhile CD4 T cell responses were observed in the spleen, which was associated with robust antibody production. Our study further supports the notion that SARS-CoV-2 N protein can work as a target for vaccine development.

2.
Proc Natl Acad Sci U S A ; 117(5): 2473-2483, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31941714

RESUMO

Neddylation is a ubiquitination-like pathway that controls cell survival and proliferation by covalently conjugating NEDD8 to lysines in specific substrate proteins. However, the physiological role of neddylation in mammalian metabolism remains elusive, and no mitochondrial targets have been identified. Here, we report that mouse models with liver-specific deficiency of NEDD8 or ubiquitin-like modifier activating enzyme 3 (UBA3), the catalytic subunit of the NEDD8-activating enzyme, exhibit neonatal death with spontaneous fatty liver as well as hepatic cellular senescence. In particular, liver-specific UBA3 deficiency leads to systemic abnormalities similar to glutaric aciduria type II (GA-II), a rare autosomal recessive inherited fatty acid oxidation disorder resulting from defects in mitochondrial electron transfer flavoproteins (ETFs: ETFA and ETFB) or the corresponding ubiquinone oxidoreductase. Neddylation inhibition by various strategies results in decreased protein levels of ETFs in neonatal livers and embryonic hepatocytes. Hepatic neddylation also enhances ETF expression in adult mice and prevents fasting-induced steatosis and mortality. Interestingly, neddylation is active in hepatic mitochondria. ETFs are neddylation substrates, and neddylation stabilizes ETFs by inhibiting their ubiquitination and degradation. Moreover, certain mutations of ETFs found in GA-II patients hinder the neddylation of these substrates. Taken together, our results reveal substrates for neddylation and add insight into GA-II.


Assuntos
Flavoproteínas Transferidoras de Elétrons/metabolismo , Ácidos Graxos/metabolismo , Fígado/metabolismo , Deficiência Múltipla de Acil Coenzima A Desidrogenase/metabolismo , Animais , Flavoproteínas Transferidoras de Elétrons/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Proteína NEDD8/genética , Proteína NEDD8/metabolismo , Oxirredução , Ubiquitinação , Ubiquitinas/genética , Ubiquitinas/metabolismo
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