Viral Control of Mitochondrial Apoptosis

Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus

In vitro antiproliferative effects of tricyclic psychopharmaceutical agents and synergism with some resistance modifiers

Some of the phenothiazines and dibenz[b,flazepines exert an antiproliferative effect on HEp-2 and rat prolactinoma cells. The same compounds also have effects on different membrane-bound biochemical events, such as H2O2 formation and the peroxide-generated chemiluminescence of polymorphonuclear leukocytes. The superoxide dismutase inhibition by 7,8-dioxochlorpromazine and 6,9-dioxochlorpromazine have some relation to the growth inhibitory action on the growth of HEP-2 and prolactinoma cells in vitro. The antiproliferative effects of phenothiazines were synergized with resistance modifers like verapamil, omeprazole and tubulozole-C, due to increased drug-influx or decreased drug-efflux and due to possible action on the cytoskeleton

The effect of interferon on chicken spleen lymphocytes

The inhibitory activity of chicken interferon has been investigated on phytohemagglutinin (PHA)-induced DNA synthesis of chicken spleen lymphocytes inoculated with type 12 adenovirus and was purified by selective adsorption on Na-Al-silicate. As a control, the culture fluid of chicken leukocytes purified in the same manner was used. In some instances the control preparation also showed a slight inhibitory effect. To prove that the immunosuppressive activity of our interferon preparation was indeed due to its interferon content both the interferon and the control preparation were purified further by chromatography on Sephadex G 100 superfine gel. Only the fractions with antiviral activity of interferon preparation inhibited the PHA-response of the lymphocytes. The fractions with the same molecular weight of control preparation were without effect