Features and Functions of the Conserved Herpesvirus Tegument Protein UL11 and Its Binding Partners.

The herpesvirus UL11 protein is encoded by the UL11 gene and is a membrane-anchored protein with multiple functions. In the last stage of viral replication, UL11 participates in the secondary envelopment process. It also plays a key role in primary envelopment, the transportation of newly assembled viral particles through cytoplasmic vesicles, and virion egress from the cell. UL11 is an important accessory protein and sometimes cooperates with other proteins that participate in virus-induced cell fusion. Cell fusion is necessary for cell-to-cell transmissions. This review summarizes the latest literature and discusses the roles of UL11 in viral assembly, primary and secondary envelopment, and cell-to-cell transmission to obtain a better understanding of the UL11 protein in the life cycle of herpesviruses and to serve as a reference for studying other viruses. Additionally, some recently discovered characteristics of UL11 are summarized.

The intracellular domain of duck plague virus glycoprotein E affects UL11 protein incorporation into viral particles.

Studies have shown that proteins in the tegument (located between the viral capsid and envelope layer) play critical roles in the assembly and budding of herpesviruses. The UL11 protein of herpesviruses is important in the process of virus particle cell entry, release, assembly and secondary envelopment. Herpesvirus glycoprotein E (gE) is involved in syncytia formation, transmission between cells and nerve invasion. In herpes simplex virus, UL11 has been shown to interact with gE. However, little is known about the relationship of duck plague virus (DPV) pUL11 and gE. In this study, we constructed DPV cytoplasmic domain (CT)-gE, and extracellular domain (ET)-gE deletion mutants, pCMV-gE, CT-gE, and ET-gE and UL11 recombinant plasmids. We found that pUL11 can interact and colocalize with gE, CT-gE and ET-gE. Together, these results highlight an important role for UL11 in the function of gE, and may also have important implications for the role of pUL11 and gE.

Two nuclear localization signals regulate intracellular localization of the duck enteritis virus UL13 protein.

Duck enteritis virus (DEV) multifunctional tegument protein UL13 is predicted to be a conserved herpesvirus protein kinase; however, little is known about its subcellular localization signal. In this study, through transfection of 2 predicted nuclear signals of DEV UL13 fused to enhanced green fluorescent protein, 2 bipartite nuclear localization signals (NLS) were identified. We found that ivermectin blocked the NLS-mediated nuclear import of DEV UL13, showing that the nuclear localization signal of DEV UL13 is a classical importin α- and ß-dependent process. We constructed a DEV UL13 mutant strain in which the NLS of DEV UL13 was deleted to explore whether deletion of the NLS affects viral replication. Amino acids 4 to 7 and 90 to 96 were predicted to be NLSs, further proving that nuclear import occurs via a classical importin α- and ß-dependent process. We also found that the NLS of pUL13 had no effect on DEV replication in cell culture. Our study enhances the understanding of DEV pUL13. Taken together, these results provide significant information regarding the biological function of pUL13 during DEV infection.

UL11 Protein Is a Key Participant of the Duck Plague Virus in Its Life Cycle.

Tegument protein UL11 plays a critical role in the life cycle of herpesviruses. The UL11 protein of herpesviruses is important for viral particle entry, release, assembly, and secondary envelopment. Lipid raft is cholesterol-rich functional microdomains in cell membranes, which plays an important role in signal transduction and substance transport. Flotillin and prohibition, which are considered to be specific markers of lipid raft. However, little is known about the function of duck plague virus (DPV) UL11 in the life cycle of the viruses and the relationship between the lipid raft and UL11. In this study, an interference plasmid shRNA126 for UL11 was used. Results showed that UL11 is involved in the replication, cell to cell spread, viral particle assembly, and release processes. Furthermore, UL11 was verified that it could interact with the lipid raft through sucrose density gradient centrifugation and that function correlates with the second glycine of the UL11. When the lipid raft was depleted using the methyl-ß-cyclodextrin, the release of the DPV was decreased. Moreover, UL11 can decrease several relative viral genes mRNA levels by qRT-PCR and Western blot test. Altogether, these results highlight an important role for UL11 protein in the viral replication cycle.

Duck enteritis virus UL21 is a late gene encoding a protein that interacts with pUL16.

BACKGROUND: pUL21 is a conserved protein of Alphaherpesvirinae that performs multiple important functions. The C-terminus of pUL21 in other members of this subfamily has RNA-binding ability; this domain contributes to pseudorabies virus (PRV) retrograde axonal transport in vitro and in vivo and participates in newly replicated viral DNA packaging and intracellular virus transport. However, knowledge regarding duck enteritis virus (DEV) pUL21 is limited. RESULTS: We verified that DEV UL21 is a γ2 gene that encodes a structural protein. Moreover, we observed that pUL21 localized to the nucleus and cytoplasm. DEV pUL21 interacted with pUL16 and formed a complex in transfected human embryonic kidney (HEK) 293 T cells and DEV-infected duck embryo fibroblasts (DEFs). These results were further confirmed by CO-IP assays. CONCLUSIONS: The DEV UL21 gene is a late gene, and pUL21 localizes to the nucleus and cytoplasm. DEV UL21 is a virion component. In addition, pUL21 can interact with pUL16. These findings provide insight into the characteristics of UL21 and the interaction between pUL21 and its binding partner pUL16. Our study enhances the understanding of DEV pUL21.

Innate Immune Evasion of Alphaherpesvirus Tegument Proteins.

Alphaherpesviruses are a large family of highly successful human and animal DNA viruses that can establish lifelong latent infection in neurons. All alphaherpesviruses have a protein-rich layer called the tegument that, connects the DNA-containing capsid to the envelope. Tegument proteins have a variety of functions, playing roles in viral entry, secondary envelopment, viral capsid nuclear transportation during infection, and immune evasion. Recently, many studies have made substantial breakthroughs in characterizing the innate immune evasion of tegument proteins. A wide range of antiviral tegument protein factors that control incoming infectious pathogens are induced by the type I interferon (IFN) signaling pathway and other innate immune responses. In this review, we discuss the immune evasion of tegument proteins with a focus on herpes simplex virus type I.

Identification of narciclasine from Lycoris radiata (L'Her.) Herb. and its inhibitory effect on LPS-induced inflammatory responses in macrophages.

Lycoris radiata (L'Her.) Herb. (L. radiata) was traditionally used as a folk medicine in China for treatment of Alzheimer's disease. However, the specific component responsible for its considerable toxicity remained unclear thus restricting its clinical trials. Narciclasine (NCS) was isolated from L. radiata and treatment of NCS for 72 h exhibited significant antiproliferative effects against L02, Hep G2, HT-29 and RAW264.7 cells. However, what needs to be emphasized is that at safe working concentrations of 0.001-0.016 µM, administration of NCS for 24 h inhibited the mRNA expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-ɑ), interleukin-1beta (IL-1ß) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced macrophages thereby suppressing production of nitric oxide (NO), IL-6, TNF-ɑ and IL-1ß. NCS supplementation also inhibited nuclear factor-kappa B (NF-κB) activation by suppressing NF-κB P65 phosphorylation and nuclear translocation, IκBɑ degradation and phosphorylation, and IκKɑ/ß phosphorylation. The phosphorylation of c-Jun N-terminal kinase (JNK) and P38, and expression of COX-2 was also attenuated by NCS. These results suggested that NCS might exert anti-inflammatory effects through inhibiting NF-κB and mitogen-activated protein kinase (MAPK) pathways even at very low doses.

Renal toxic ingredients and their toxicology from traditional Chinese medicine.

INTRODUCTION: There have been increasing concerns regarding adverse reactions and toxicity incidents caused by traditional Chinese medicines (TCMs), among which the nephrotoxicity is particularly worrying. AREAS COVERED: This review summarizes the ingredients with renal toxicity from some TCMs through searching the relevant literature published over the past two decades. Renal toxicity components from TCMs include aristolochic acids (AAS), alkaloids, anthraquinones and others. TCM renal toxicity is most commonly caused by AAS and some alkaloids. AAS mainly come from Aristolochia contorta Bunge, Aristolochia manshuriensis Kom, Clematis Chinensis Osbeck, Aristolochia cathcartii Hook. Some renal toxic alkaloids are derived from Tripterygium regelii Sprague et Takeda, Stephania tetrandra S. Moore, Strychnos nux-vomica Linn. and Aconitum carmichaeli Debx. A few kinds of anthraquinones, flavonoids, and glycosides from TCMs also cause renal toxicity. All of these renal toxicity components and their associated renal toxicity, structures and toxic mechanism are introduced in detail in this review. EXPERT OPINION: Given the complexity of the toxic components, a lot of work needs to be done to analyze the specific modes of action of toxic components in vivo and in vitro, in particular, to elucidate the molecular mechanism of toxicity, in order to reduce the occurrence of renal toxicity of TCM.