Progress on innate immune evasion and live attenuated vaccine of pseudorabies virus.

Pseudorabies virus (PRV) is a highly infectious disease that can infect most mammals, with pigs as the only natural host, has caused considerable economic losses to the pig husbandry of the world. Innate immunity is the first defense line of the host against the attack of pathogens and is essential for the proper establishment of adaptive immunity. The host uses the innate immune response to against the invasion of PRV; however PRV makes use of various strategies to inhibit the innate immunity to promote the virus replication. Currently, live attenuated vaccine is used to prevent pig from infection with the PRV worldwide, such as Bartha K61. However, a growing number of data indicates that these vaccines do not provide complete protection against new PRV variants that have emerged since late 2011. Here we summarized the interactions between PRV and host innate immunity and the current status of live attenuated PRV vaccines to promote the development of novel and more effective PRV vaccines.

Nutrient availability of roughages in isocaloric and isonitrogenous diets alters the bacterial networks in the whole gastrointestinal tract of Hu sheep.

BACKGROUND: The nutrient availability of roughages could affect the dietary utilization efficiency of ruminants even in isocaloric and isonitrogenous diets. Here, we analyzed the bacterial composition and their metabolic pathways in the gastrointestinal tracts (GITs) of Hu sheep fed with wheat straw (WS) instead of alfalfa (AL) in isocaloric and isonitrogenous diets, trying to explore the reasons from the perspective of GITs bacterial network structure changes. RESULTS: We employed 16S rRNA gene sequencing in combination with the Kruskal-Wallis test, Spearman correlation analysis, and other statistical methods to describe the microbiota composition in the GITs of Hu sheep. The results showed after the roughage was replaced from AL to WS, the most positive response occurred in the rumen microbiota, resulting in a more obvious microbiological and functional redundancy phenomenon. Whereas extended biogeographic studies of the GITs bacterial community found opposite results for the hindgut microbiota and metabolism networks compared to the forestomach. The abundance of fiber-degrading bacteria such as Prevotella, Oscillospiraceae NK4A214 group, and Treponema was significantly increased in GITs, but low-efficiency crude fiber degradation inhibited energy use efficiency, the pentose phosphate pathway, gluconeogenesis, and volatile acid synthesis. In addition, dietary shifting from AL to WS decreased the abundance of beneficial bacteria such as the Lachnospiraceae NK3A20 group and Alistipes, thereby enhancing the underlying inflammatory response. CONCLUSIONS: These findings suggest that feeding untreated WS affected the structure and function of the bacterial network in the GITs due to limited total digestible nutrients, and in particular increases the complexity of the rumen bacterial network, and limit the abundance of bacteria involved in the crude fiber degradation in the hindgut.

A Glycolipid α-GalCer Derivative, 7DW8-5 as a Novel Mucosal Adjuvant for the Split Inactivated Influenza Vaccine.

Influenza virus infects the host and transmits through the respiratory tract (i.e., the mouth and nose); therefore, the development of intranasal influenza vaccines that mimic the natural infection, coupled with an efficient mucosal adjuvant, is an attractive alternative to current parenteral vaccines. However, with the withdrawal of cholera toxin and Escherichia coli heat-labile endotoxin from clinical use due to side effects, there are no approved adjuvants for intranasal vaccines. Therefore, safe and effective mucosal adjuvants are urgently needed. Previously, we reported that one derivative of α-Galactosylceramide (α-GalCer), 7DW8-5, could enhance the protective efficacy of split influenza vaccine by injection administration. However, the mucosal adjuvanticity of 7DW8-5 is still unclear. In this study, we found that 7DW8-5 promotes the production of secret IgA antibodies and IgG antibodies and enhances the protective efficacy of the split influenza vaccine by intranasal administration. Furthermore, co-administration of 7DW8-5 with the split influenza vaccine significantly reduces the virus shedding in the upper and lower respiratory tract after lethal challenge. Our results demonstrate that 7DW8-5 is a novel mucosal adjuvant for the split influenza vaccine.

KAP1 Positively Modulates Influenza A Virus Replication by Interacting with PB2 and NS1 Proteins in Human Lung Epithelial Cells.

Influenza virus only encodes a dozen of viral proteins, which need to use host machinery to complete the viral life cycle. Previously, KAP1 was identified as one host protein that potentially interacts with influenza viral proteins in HEK 293 cells. However, the role of KAP1 in influenza virus replication in human lung alveolar epithelial cells and the underlying mechanism remains unclear. In this study, we first generated KAP1 KO A549 cells by CRISPR/Cas9 gene editing. KAP1 deletion had no significant effect on the cell viability and lack of KAP1 expression significantly reduced the influenza A virus replication. Moreover, we demonstrated that KAP1 is involved in the influenza virus entry, transcription/replication of viral genome, and viral protein synthesis in human lung epithelial cells and confirmed that KAP1 interacted with PB2 and NS1 viral proteins during the virus infection. Further study showed that KAP1 inhibited the production of type I IFN and overexpression of KAP1 significantly reduced the IFN-ß production. In addition, influenza virus infection induces the deSUMOylation and enhanced phosphorylation of KAP1. Our results suggested that KAP1 is required for the replication of influenza A virus and mediates the replication of influenza A virus by facilitating viral infectivity and synthesis of viral proteins, enhancing viral polymerase activity, and inhibiting the type I IFN production.

The biotechnological potential of anaerobic fungi on fiber degradation and methane production.

Anaerobic fungi (phylum Neocallimastigomycota), an early branching family of fungi, are commonly encountered in the digestive tract of mammalian herbivores. To date, isolates from ten described genera have been reported, and several novel taxonomic groupings are detected using culture-independent molecular methods. Anaerobic fungi are recognized as playing key roles in the decomposition of lignocellulose (up to 50% of the ingested and untreated lignocellulose), with their physical penetration and extracellular enzymatical secretion of an unbiased diverse repertoire of cell-wall-degrading enzymes. The secreted cell-wall-degrading enzymes of anaerobic fungi include both free enzymes and extracellular multi-enzyme complexes called cellulosomes, both of which have potential as fiber degraders in industries. In addition, anaerobic fungi can provide large amounts of substrates such as hydrogen, formate, and acetate for their co-cultured methanogens. Consequently, large amounts of methane can be produced. And thus, it is promising to use the co-culture of anaerobic fungi and methanogens in the biogas process to intensify the biogas yield owing to the efficient and robust degradation of recalcitrant biomass by anaerobic fungi and improved methane production from co-cultures of anaerobic fungi and methanogens.