Importance of Promyelocytic Leukema Protein (PML) for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication

Many DNA virus replication-related proteins are associated with promyelocytic leukemia protein (PML), a component of nuclear domain 10 (ND10), which has been investigated for its potential involvement in viral replication. In the case of Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic gene products, K8 (K-bZIP), ORF59, and ORF75 have been shown to colocalize with PML, but its importance in KSHV lytic replication is still unclear. In this study, we analyzed the functional influence of PML on KSHV latency and lytic replication in KSHV-infected primary effusion lymphoma (PEL) cell lines. Stable PML-knockout (BC3-PMLKO) and PML-overexpressing BC3 cells (BC3PML) were successfully generated and the latency and reactivation status were analyzed. The results demonstrated that neither KSHV latency nor the episome copy number was affected in BC3-PMLKO cells. In the reactivation phase, the expression dynamics of KSHV immediate-early or early lytic proteins such as RTA, K9 (vIRF1), K5, K3, ORF59, and K8 (K-bZIP) were comparable between wild-type, control BC3, and BC3-PMLKO cells. Interestingly, KSHV lytic replication, virion production, and expression of late genes were downregulated in BC3-PMLKO cells and upregulated in BC3PML cells, compared to those in control or wild-type BC3 cells. Moreover, exogenous PML increased the size of the PML dots and recruited additional K8 (K-bZIP) to PML-NBs as dots. Therefore, PML would function as a positive regulator for KSHV lytic DNA replication by recruiting KSHV replication factors such as 8 (K-bZIP) or ORF59 to the PML-NBs

Mixed-metal Cluster Synthesis: [Re(CO)\u3csub\u3e3\u3c/sub\u3e(μ-S\u3csub\u3e2\u3c/sub\u3eNC\u3csub\u3e7\u3c/sub\u3eH\u3csub\u3e4\u3c/sub\u3e)]\u3csub\u3e2\u3c/sub\u3e as a Precursor for tri- and tetranuclear 2-mercaptobenzothiolato Capped Clusters

The readily prepared [Re2(CO)6(μ-S2NC7H4)2] (1) reacts with Group 8 trimetallic carbonyl clusters to yield new mixed-metal tri- and tetranuclear clusters. With [Os3(CO)10(NCMe)2] at 80 °C the tetranuclear mixed-metal cluster [Os3Re(CO)13(μ3-C7H4NS2)] (2) is the only isolated product. With Ru3(CO)12 products are dependent upon the reaction temperature. At 80 °C, a mixture of tetranuclear mixed-metal [Ru3Re(CO)13(μ3-C7H4NS2)] (5) and the triruthenium complex [Ru3(CO)9(μ-H)(μ3-C7H4NS2)] (4) results, while at 110 °C a second tetranuclear mixed-metal cluster, [Re2Ru2(CO)12(μ4-S)(μ-C7H4NS)(μ-C7H4NS2)] (3), resulting from carbon–sulfur bond scission, is the major product. Reaction of 1 With Fe3(CO)12 at 80 °C furnishes the trinuclear mixed-metal cluster [Fe2Re(CO)8(μ-CO)2(μ3-C7H4NS2)] (6). The reactivity of 6 has been probed with the aim of identifying any metal-based selectivity for carbonyl substitution. Addition of PPh3 in presence of Me3NO at 25 °C gives both the mono- and bis(phosphine)-substituted derivatives [Os3Re(CO)12(PPh3)(μ3-C7H4NS2)] (7) and [Os3Re(CO)11(PPh3)2(μ3-C7H4NS2)] (8). In 7 the PPh3 ligand occupies an axial site on wingtip osmium, while in 8 one PPh3 ligand is equatorially coordinated to wingtip osmium and the other is bonded to a hinge osmium. New complexes have been characterized by a combination of spectroscopic data and single crystal X-ray diffraction studies

Corrigendum: Insights into the coinfections of human immunodeficiency virus-hepatitis B virus, human immunodeficiency virus-hepatitis C virus, and hepatitis B virus-hepatitis C virus: prevalence, risk factors, pathogenesis, diagnosis, and treatment

Human immunodeficiency virus, hepatitis B virus, and hepatitis C virus are three blood-borne viruses that can cause major global health issues by increasing severe morbidity. There is a high risk of coinfection with these viruses in individuals because of their same transmission routes through blood using shared needles, syringes, other injection equipment, sexual transmission, or even vertical transmission. Coinfection can cause various liver-related illnesses, non-hepatic organ dysfunction, followed by death compared to any of these single infections. The treatment of coinfected patients is complicated due to the side effects of antiviral medication, resulting in drug resistance, hepatotoxicity, and a lack of required responses. On the other hand, coinfected individuals must be treated with multiple drugs simultaneously, such as for HIV either along with HBV or HCV and HBV and HCV. Therefore, diagnosing, treating, and controlling dual infections with HIV, HBV, or HCV is complicated and needs further investigation. This review focuses on the current prevalence, risk factors, and pathogenesis of dual infections with HIV, HBV, and HCV. We also briefly overviewed the diagnosis and treatment of coinfections of these three blood-borne viruses

Investigation of a Novel Hepatitis B Virus Surface Antigen (HBsAg) Escape Mutant Affecting Immunogenicity.

Mutation in the hepatitis B virus surface antigen (HBsAg) may affect the efficiency of diagnostic immunoassays or success of vaccinations using HBsAg. Thus, antigenicity and immunogenicity analyses of the mutated HBsAg are necessary to develop novel diagnostic tools and efficient vaccinations. Here, the in vitro antigenicity of three wild-type HBsAg open reading frames (ORFs) (adr4, W1S [subtype adr] and W3S [subtype adr]) isolated from clinically infected patients and nineteen synthesized single/double/multiple amino acid-substituted mutants were tested with commercial ELISA kits. Immunofluorescence staining of transfected cells and Western blot analysis confirmed that these ORFs were expressed at comparable levels in HEK-293 cells. W1S and adr4 were clearly detected, whereas W3S could not be detected. Using the same commercial immunoassay kit, we found that the single mutants, K120P and D123T, were marginally reactive, whereas W3S-aW1S and the double mutant, K120P/D123T, exhibited antigenicity roughly equivalent to the wild-type wako1S. On the other hand, the single mutants of W1S, P120K and T123D, significantly impaired the reactivity, while W1S-aW3S and the double mutant of W1S, P120K/T123D, resulted in a complete loss of antigenicity. In addition, ELISA revealed reduced HBs antigenicity of two mutants, W1S N146G and W1S Q129R/G145R. These commercial ELISA-based antigenic reactivities of HBsAg were also strongly correlated with the predicted Ai alterations of affected amino acids due to the specific mutation. In conclusion, this study showed for the first time that lysine (K120) and aspartate (D123) simultaneously affected HBsAg antigenicity, leading to diagnostic failure. These findings will improve diagnostic assays and vaccine development

Emerging Role of Neuropilin-1 and Angiotensin-Converting Enzyme-2 in Renal Carcinoma-Associated COVID-19 Pathogenesis

Neuropilin-1 (NRP1) is a recently identified glycoprotein that is an important host factor for SARS-CoV-2 infection. On the other hand, angiotensin-converting enzyme-2 (ACE2) acts as a receptor for SARS-CoV-2. Additionally, both NRP1 and ACE2 express in the kidney and are associated with various renal diseases, including renal carcinoma. Therefore, the expression profiles of NRP1 and ACE2 in kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) patients from the various cancer databases were investigated along with their impact on patients’ survivability. In addition, coexpression analysis of genes involved in COVID-19, KIRC, and KIRP concerning NRP1 and ACE2 was performed. The results demonstrated that both t NRP1 and ACE2 expressions are upregulated in KIRC and KIRP compared to healthy conditions and are significantly correlated with the survivability rate of KIRC patients. A total of 128 COVID-19-associated genes are coexpressed, which are positively associated with NRP1 and ACE2 both in KIRC and KIRP. Therefore, it might be suggested that, along with the ACE2, high expression of the newly identified host factor NRP1 in renal carcinomas may play a vital role in the increased risk of SARS-CoV-2 infection and survivability of COVID-19 patients suffering from kidney cancers. The findings of this investigation will be helpful for further molecular studies and prevention and/or treatment strategies for COVID-19 patients associated with renal carcinomas

Antigenicity index (A<i>i</i>) prediction of HBsAg with Jameson-Wolf algorithm within amino acids 110–160.

<p>Antigenicity index (A<i>i</i>) prediction of HBsAg with Jameson-Wolf algorithm within amino acids 110–160.</p

Expression of the wild-type HBsAg.

<p>(A) Western blotting analysis. HEK293-T cells were transfected with plasmid vectors expressing the wild-type HBsAgs (W1S, W3S and adr4). The expressed HBsAgs were purified from the culture supernatants and the cell lysates 72 h after transfection and an equal volume of each sample was run on SDS-PAGE. An anti-Xpress mAb against the Xpress tag was used to detect each HBsAg. (B) Immunofluorescence assay. Cells on the culture slides were fixed 72 h after transfection and stained with an anti-Xpress mAb as for the Western blot followed by an anti-mouse IgG conjugated with Alexa Fluor 488. Cell nuclei were stained with DAPI. Non-transfected cells were used as a negative control (NC). Each experiment was performed independently three times and one representative result is shown. wt: wild-type.</p