K64 acetylation of heat shock protein 90 suppresses nucleopolyhedrovirus replication in Bombyx mori.

HSP90 is a highly conserved chaperone that facilitates the proliferation of many viruses, including silkworm (bombyx mori) nucleopolyhedrovirus (BmNPV), but the underlying regulatory mechanism was unclear. We found that suppression of HSP90 by 17-AAG, a HSP90-specific inhibitor, significantly reduced the expression of BmNPV capsid protein gp64 and viral genome replication, whereas overexpression of B. mori HSP90(BmHSP90) promoted BmNPV replication. Furthermore, in a recent study of the lysine acetylome of B. mori infected with BmNPV, we focused on the reduced viral proliferation due to changes of BmHSP90 lysine acetylation. Site-directed introduction of acetylated (K/Q) or deacetylated (K/R) mimic mutations into BmHSP90 revealed that lysine 64 (K64) acetylation activated the JAK/STAT pathway and reduced BmHSP90 ATPase activity, leading to diminished chaperone activity and ultimately inhibiting BmNPV proliferation. In this study, a single lysine 64 acetylation change of BmHSP90 was elucidated as a model of posttranslational modifications occurring in the wake of host-virus interactions, providing novel insights into potential antiviral strategies.

Deacetylation of ACO2 Is Essential for Inhibiting Bombyx mori Nucleopolyhedrovirus Propagation.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a specific pathogen of Bombyx mori that can significantly impede agricultural development. Accumulating evidence indicates that the viral proliferation in the host requires an ample supply of energy. However, the correlative reports of baculovirus are deficient, especially on the acetylation modification of tricarboxylic acid cycle (TCA cycle) metabolic enzymes. Our recent quantitative analysis of protein acetylome revealed that mitochondrial aconitase (ACO2) could be modified by (de)acetylation at lysine 56 (K56) during the BmNPV infection; however, the underlying mechanism is yet unknown. In order to understand this regulatory mechanism, the modification site K56 was mutated to arginine (Lys56Arg; K56R) to mimic deacetylated lysine. The results showed that mimic deacetylated mitochondrial ACO2 restricted enzymatic activity. Although the ATP production was enhanced after viral infection, K56 deacetylation of ACO2 suppressed BmN cellular ATP levels and mitochondrial membrane potential by affecting citrate synthase and isocitrate dehydrogenase activities compared with wild-type ACO2. Furthermore, the deacetylation of exogenous ACO2 lowered BmNPV replication and generation of progeny viruses. In summary, our study on ACO2 revealed the potential mechanism underlying WT ACO2 promotes the proliferation of BmNPV and K56 deacetylation of ACO2 eliminates this promotional effect, which might provide novel insights for developing antiviral strategies.

TAT-modified self-assembled cationic peptide nanoparticles as an efficient antibacterial agent.

The increasing emergence of drug resistant pathogenic bacteria poses a great challenge to clinical therapy and a threat to public health. Cationic peptides have received great attention for their unique antibacterial mechanism and ability to combat drug-resistant bacteria. In this study, we designed a TAT-modified cationic peptide PA-28 which self-assembled into nanoparticles of about 150 nm. These nanoparticles showed strong antimicrobial activities against both gram-positive and gram-negative bacteria, including drug-resistant bacteria. They were more potent than the unassembled counterpart peptide nonalysine (K9). Their antibacterial mechanism of directly destructing bacterial wall/membrane reduces the possibility of developing bacterial resistance. In vivo anti-infective experiments showed that these nanoparticles were able to penetrate the blood-brain barrier to inhibit bacterial growth in infected brains of rats. In addition, these nanoparticles induced low hemolysis below the minimum inhibitory concentration. Therefore, the peptide designed in this study is a promising and efficient antibacterial agent against bacterial infections.