Chimeric Rabbit Anti-RSV pre-fusion conformation of HRSV F protein monoclonal antibody, clone STC30

Resveratrol (RSV) and long non-coding RNAs (lncRNAs) play a role in the treatment of diabetes; however, the mechanism by which resveratrol regulates insulin resistance via lncRNAs is currently unknown. The present study aimed to determine the lncRNA expression level profile in mice following resveratrol treatment to improve insulin resistance using high-throughput sequencing technology. C57BL/6J mice were fed a high-fat diet for 8 weeks to develop an insulin resistance model, followed by treatment with or without RSV for 6 weeks before high-throughput sequencing. Following RSV treatment, 28 and 30 lncRNAs were up- and downregulated, respectively; eight lncRNAs were randomly selected and evaluated using reverse transcription-quantitative PCR, which showed results consistent with the sequencing analysis. Pathway analysis demonstrated that the insulin signaling pathway enrichment score was the highest, and identified two lncRNAs, NONMMUT058999.2 and NONMMUT051901.2, consistent with the protein-encoding genes SOCS3 and G6PC, respectively. Similar expression level patterns were observed for SOCS3 and G6PC, suggesting that RSV improves insulin resistance by modulating lncRNAs. RSV decreased the expression levels of SOCS3, FOXO1, G6PC and PEPCK in mice. The same results were observed following knockdown of NONMMUT058999.2 in cells. The present study provides a new biomarker or intervention target for RSV in the treatment of diabetes, and a new perspective for understanding the hypoglycemic mechanism of RSV.

Retroviral Gag polyproteins orchestrate the assembly and release of nascent virus particles from the plasma membranes of infected cells. Although it was traditionally thought that Gag proteins trafficked directly from the cytosol to the plasma membrane, we discovered that the oncogenic avian alpharetrovirus Rous sarcoma virus (RSV) Gag protein undergoes transient nucleocytoplasmic transport as an intrinsic step in virus assembly. Using a genetic approach in yeast, we identified three karyopherins that engage the two independent nuclear localization signals (NLSs) in Gag. The primary NLS is in the nucleocapsid (NC) domain of Gag and binds directly to importin-alpha, which recruits importin-beta to mediate nuclear entry. The second NLS (TNPO3), which resides in the matrix (MA) domain, is dependent on importin-11 and transportin-3 (TNPO3), which are known as MTR10p and Kap120p in yeast, although it is not clear whether these import factors are independent or additive. The functions of importin-alpha/importin-beta and importin-11 have been verified in avian cells, whereas the role of TNPO3 has not been studied. In this report, we demonstrate that TNPO3 directly binds to Gag and mediates its nuclear entry. To our surprise, this interaction did not require the cargo-binding domain (CBD) of TNPO3, which typically mediates nuclear entry for other binding partners of TNPO3, including SR domain-containing splicing factors and tRNAs that reenter the nucleus. These results suggest that RSV hijacks this host nuclear import pathway using a unique mechanism, potentially allowing other cargo to simultaneously bind TNPO3. IMPORTANCE RSV Gag nuclear entry is facilitated using three distinct host import factors that interact with nuclear localization signals in the Gag MA and NC domains. Here, we show that the MA region is required for nuclear import of Gag through the TNPO3 pathway. Gag nuclear entry does not require the CBD of TNPO3. Understanding the molecular basis for TNPO3-mediated nuclear trafficking of the RSV Gag protein may lead to a deeper appreciation for whether different import factors play distinct roles in retrovirus replication.