Additional Insertion of gC Gene Triggers Better Immune Efficacy of TK/gI/gE-Deleted Pseudorabies Virus in Mice.

In recent years, pseudorabies virus (PRV) variants have resulted in an epidemic in swine herds and huge economic losses in China. Therefore, it is essential to develop an efficacious vaccine against the spread of PRV variants. Here, the triple-gene-deletion virus and the triple-gene-deletion plus gC virus were constructed by homologous recombination (HR). And then, their growth capacity, proliferation ability, and immune efficacy were evaluated. The results showed that the growth kinetics of the recombinant viruses were similar to those of the parental strain PRV-AH. Compared with the triple-gene-deletion virus group, the more dominant level of neutralizing antibody (NA) can be induced in the triple-gene-deletion plus gC virus group with the same 106.0 TCID50 dose after 4 and 6 weeks post-initial immunization (PII) (p < 0.0001). In addition, the antibody titers in mice immunized with the triple-gene-deletion plus gC virus were significantly higher than those immunized with triple-gene deletion virus with the same 105.0 TCID50 dose after 6 weeks PII (p < 0.001). More importantly, in the triple-gene-deletion plus gC virus group with 105.0 TCID50, the level of NA was close to that in the triple-gene deletion virus group with 106.0 TCID50 at 6 weeks PII. Meanwhile, the cytokines IL-4 and IFN-γ in sera were tested by enzyme-linked immunosorbent assay (ELISA) in each group. The highest level of IL-4 or IFN-γ was also elicited in the triple-gene deletion plus gC virus group at a dose of 106.0 TCID50. After challenge with PRV-AH, the survival rates of the triple-gene deletion plus gC virus immunized groups were higher than those of other groups. In immunized groups with 105.0 TCID50, the survival rate shows a significant difference between the triple-gene deletion plus gC virus group (75%, 6/8) and the triple-gene deletion virus group (12.5%, 1/8). In general, the immune efficacy of the PRV TK/gI/gE-deleted virus can be increased with additional gC insertion in mice, which has potential for developing an attenuated vaccine candidate for PRV control.

The Role of Latency-Associated Transcripts in the Latent Infection of Pseudorabies Virus.

Pseudorabies virus (PRV) can cause neurological, respiratory, and reproductive diseases in pigs and establish lifelong latent infection in the peripheral nervous system (PNS). Latent infection is a typical feature of PRV, which brings great difficulties to the prevention, control, and eradication of pseudorabies. The integral mechanism of latent infection is still unclear. Latency-associated transcripts (LAT) gene is the only transcriptional region during latent infection of PRV which plays the key role in regulating viral latent infection and inhibiting apoptosis. Here, we review the characteristics of PRV latent infection and the transcriptional characteristics of the LAT gene. We also analyzed the function of non-coding RNA (ncRNA) produced by the LAT gene and its importance in latent infection. Furthermore, we provided possible strategies to solve the problem of latent infection of virulent PRV strains in the host. In short, the detailed mechanism of PRV latent infection needs to be further studied and elucidated.

Behavioral changes over time in post-traumatic stress disorder: Insights from a rat model of single prolonged stress.

Post-traumatic stress disorder (PTSD) is manifested as a persistent mental and emotional condition after potentially life-threatening events. Different animal models of PTSD have been developed for neuro-pathophysiology and pharmacological evaluations. A single prolonged stress (SPS) induced animal model has demonstrated to result in specific neuro-endocrinological dysregulation, and behavior abnormalities observed in PTSD. However, animal studies of PTSD have mostly been performed at one time point after SPS exposure. To better understand the development of PTSD-like behaviors in the SPS animal model, and to identify an optimal period of study, we examined depressive behavior, anxiety-like behavior, physical activity and body weight in SPS model rats for two weeks. Our results confirmed the SPS-induced PTSD-like behavior and physical activity observed in previous studies, and indicated that the most pronounced symptomatic behavior changes were observed on day 1 and 7 after SPS exposure, which may involve stress-induced acute hormone changes and unclear secondary neurobiological changes, respectively. These results provide a solid basis for further investigation into the neuro-pathophysiology of or neuropharmacology for PTSD using the SPS rat model. However, for chronic (pharmacological) studies longer than 7 days, a prolonged PTSD animal model should be developed, perhaps using enhanced stimulation.

Sini powder () decoction alleviates mood disorder of insomnia by regulating cation-chloride cotransporters in hippocampus.

OBJECTIVE: To investigate the mechanism of Sini Powder () decoction (SND) in the treatment of insomnia. METHODS: The rats were randomly divided into four groups: control, model, SND-treated, and Estazolamtreated groups (n=15 in each group). Sleep deprivation (SD) rat model was established using the modifified multiple platform method for 14 h per day for 14 days, and the behavior of the rats were observed. Na-K-Cl-cotransporter (NKCC1) and K+/Cl- cotransporter (KCC2) in the hippocampus were tested by immunohistochemistry, real-time polymerase chain reaction, and western blot. RESULTS: SD rats displayed anxiety-like behavior, which was alleviated by SND. The protein expressions of NKCC1 and KCC2 in the hippocampus were signifificantly decreased in SD rats compared with those in control rats (P<0.05); these proteins were signifificantly increased by SND (P<0.05). The mRNA expression of KCC2 was signifificantly decreased in SD rats (0.62±0.35 vs. 2.29±0.56; P=0.044), while SND showed a tendency to increase the mRNA of KCC2 in SD rats (P>0.05). By contrast, the mRNA expression of NKCC1 was signifificantly increased in the hippocampus of SD rats (6.58±1.54 vs. 2.82±0.32; P=0.011), while SND decreased the mRNA expression of NKCC1 (6.58±1.54 vs. 2.79±0.81; P=0.016). CONCLUSIONS: Chinese medicine SND could alleviate mood disorder of SD rats by regulating cation-chloride cotransporters, such as NKCC1 and KCC2. These fifindings would have major implications in the mechanism of SND to relieve insomnia.