Cardioprotective Effects of SIRT6 in a Mouse Model of Transverse Aortic Constriction-Induced Heart Failure.

SIRT6, a member of the NAD (+)-dependent class III deacetylase sirtuin family, plays important roles in the maintenance of cardiovascular homeostasis. Telomere shortening is a risk factor for age-associated diseases, including heart disease. In the present study, we investigated the role of SIRT6 and telomerase in a mouse model of transverse aortic constriction (TAC)-induced heart failure. SIRT6, telomerase reverse transcriptase (TERT), and telomere repeat binding factor (TRF)-1 were significantly downregulated in TAC mice compared with their expression in sham-operated mice. Lentiviral vector-mediated overexpression of SIRT6 upregulated TERT and TRF1 and increased the survival of mice after TAC. Echocardiography and hemodynamic measurements as well as histological analyses indicated that SIRT6 overexpression attenuated TAC-induced heart dysfunction and decreased TAC-induced cardiac inflammatory responses, reducing cardiac fibrosis and decreasing infarct size. Taken together, our findings indicate that SIRT6 protects the myocardium against damage and this effect may be mediated by the modulation of telomeres. Our findings linking SIRT6 and telomere integrity in the heart warrant further investigation into the underlying mechanisms and support SIRT6 as a promising therapeutic target for the treatment of cardiovascular diseases.

Effect on virulence and pathogenicity of H5N1 influenza A virus through truncations of NS1 eIF4GI binding domain.

To study the effect of NS1 eIF4GI binding domain on virulence and pathogenicity of H5N1 influenza A virus, 5 recombinant H5N1 viruses encoding eIF4GI binding domain-truncated NS1 proteins and parental NS1 (NS1­wt) were generated by an 8­plasmid-based reverse genetics system. The results indicated that the recombinants with the addition of 5­amino acid and the deletion position of 85-89 in NS1­wt were attenuated in replication in vitro and in vivo, compared with the recombinant wild­type virus rNS1­wt, whereas the deletion position 85-94 or the entire eIF4GI binding domain in NS1­wt displayed a significantly attenuated phenotype in chicken and mice. We also showed that the eIF4GI binding domain-truncated mutants were impaired in their ability to inhibit interferon production in vitro, and they did not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in Madin ­Darby Canine Kidney cells, or in vivo in chickens and in a mouse model. Therefore, these attenuated NS1­truncated viruses may have a great potential as live attenuated vaccine candidates against H5N1 influenza A virus.

Screening of proteins interacting with avian influenza virus nucleoprotein by yeast two-hybrid system in human brain cDNA library / 生物工程学报

Avian influenza virus Nucleoprotein (NP) is important in viral transcription, replication and determining host specificity of influenza virus. Yeast two-hybrid technique was applied to screen for proteins interacting with virus nucleoprotein, so as to further elucidate the interaction between virus nucleoprotein and cellular proteins, as well as the interaction between virus and host. To explore new proteins interacted with NP protein, a human brain cDNA library was screened using yeast two-hybrid system with NP as the bait. DNA inserts of the positive AD/library plasmids were sequenced. By the BLAST analysis against the GenBank databases seven positive clones resulted in seven genes. Our results could help for the further study on the molecular mechanism of virus replication, transcription and protein-protein interaction. Further investigations were needed to characterize these interactions.