A mechanism decreasing oxidative metabolism during normal cell division and growth is expected to direct substrates toward biosyntheses rather than toward complete oxidation to CO ₂ . Hence, any event decreasing oxidative phosphorylations (OXPHOS) could provide a proliferating advantage to a transformed or tumor cell in an oxidative tissue. To test this hypothesis, we studied mitochondrial enzymes, DNA and OXPHOS protein content in three types of renal tumors from 25 patients. Renal cell carcinomas (RCCs) of clear cell type (CCRCCs) originate from the proximal tubule and are most aggressive. Chromophilic RCCs, from similar proximal origin, are less aggressive. The benign renal oncocytomas originate from collecting duct cells. Mitochondrial enzyme and DNA contents in all tumor types or grades differed significantly from normal tissue. Mitochondrial impairment increased from the less aggressive to the most aggressive RCCs, and correlated with a considerably decreased content of OXPHOS complexes (complexes II, III, and IV of the respiratory chain, and ATPase/ATP synthase) rather than to the mitochondrial content (citrate synthase and mitochondrial (mt)DNA). In benign oncocytoma, some mitochondrial parameters (mtDNA, citrate synthase, and complex IV) were increased 4- to 7-fold, and some were slightly increased by a factor of 2 (complex V) or close to normal (complexes II and III). A low content of complex V protein was found in all CCRCC and chromophilic tumors studied. However F ₁ -ATPase activity was not consistently decreased and its impairment was associated with increased aggressiveness in CCRCCs. Immunodetection of free F ₁ -sector of complex V demonstrated a disturbed assembly/stability of complex V in several CCRCC and chromophilic tumors. All results are in agreement with the hypothesis that a decreased OXPHOS capacity favors faster growth or increased invasiveness.

The current outbreak of Ebola virus (EBOV) in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC) demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV.

VP30 is a phosphoprotein essential for the initiation of Ebola virus transcription. In this work, we have studied the effect of mutations in VP30 phosphorylation sites on the ebolavirus replication cycle by using a reverse genetics system. We demonstrate that VP30 is involved in reinitiation of gene transcription and that this activity is affected by mutations at the phosphorylation sites.

Transient expression of Ebola virus (EBOV) glycoprotein GP causes downregulation of surface proteins, cell rounding and detachment, a phenomenon believed to play a central role in the pathogenicity of the virus. In this study, evidence that moderate expression of GP does not result in such morphological changes was provided. It was shown that GP continuously produced in 293T cells from the Kunjin virus replicon was correctly processed and transported to the plasma membrane without affecting the surface expression of β1 and α5 integrins and major histocompatibility complex I molecules. The level of GP expression in Kunjin replicon GP-expressing cells was similar to that observed in cells infected with EBOV early in infection and lower than that produced in cells transfected with plasmid DNA, phCMV-GP, expressing GP from a strong promoter. Importantly, transient transfection of Kunjin replicon GP-expressing cells with GP-coding plasmid DNA resulted in overexpression of GP, which lead to the downregulation of surface molecules and massive rounding and detachment of transfected cells. Here, it was also demonstrated that cell rounding and downregulation of the surface markers are the late events in EBOV infection, whereas synthesis and massive release of virus particles occur at early steps and do not cause significant cytotoxic effects. These findings indicate that the synthesis of EBOV GP in virus-infected cells is controlled well by several mechanisms that do not allow GP overexpression and hence the early appearance of its cytotoxic properties.

Hepatitis C infection is the leading cause of liver diseases worldwide and a major health concern that affects an estimated 3% of the global population. Novel therapies available since 2014 and 2017 are very efficient and the WHO considers HCV eradication possible by the year 2030. These treatments are based on the so-called direct acting antivirals (DAAs) that have been developed through research efforts by academia and industry since the 1990s. After a brief overview of the HCV life cycle, we describe here the functions of the different targets of current DAAs, the mode of action of these DAAs and potential future inhibitors.

Ebola virus (EBOV) transcription is dependent on the phosphoprotein VP30, a component of the viral nucleocapsid. VP30 is phosphorylated at 2 serine residue clusters located at the N-terminal part of the protein. In this report, we have investigated the role of VP30 phosphorylation in EBOV replication using a reverse genetics approach. In effect, recombinant EBOVs with the VP30 serine clusters substituted either by nonphosphorylatable alanines or phosphorylation-mimicking aspartates were generated and characterized. We show that in comparison to the wild-type EBOV the mutated viruses possess reduced infectivity. This difference is explained by alterations in the balance between the transcription and replication processes and appear to be associated with the state of VP30 phosphorylation. Here we propose a model in which dynamic phosphorylation of VP30 is an important mechanism to regulate the EBOV replication cycle.