Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice.

ABT-263 and its structural analogues ABT-199 and ABT-737 inhibit B-cell lymphoma 2 (Bcl-2), BCL2L1 long isoform (Bcl-xL) and BCL2L2 (Bcl-w) proteins and promote cancer cell death. Here, we show that at non-cytotoxic concentrations, these small molecules accelerate the deaths of non-cancerous cells infected with influenza A virus (IAV) or other viruses. In particular, we demonstrate that ABT-263 altered Bcl-xL interactions with Bcl-2 antagonist of cell death (Bad), Bcl-2-associated X protein (Bax), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA). ABT-263 thereby activated the caspase-9-mediated mitochondria-initiated apoptosis pathway, which, together with the IAV-initiated caspase-8-mediated apoptosis pathway, triggered the deaths of IAV-infected cells. Our results also indicate that Bcl-xL, Bcl-2 and Bcl-w interact with pattern recognition receptors (PRRs) that sense virus constituents to regulate cellular apoptosis. Importantly, premature killing of IAV-infected cells by ABT-263 attenuated the production of key pro-inflammatory and antiviral cytokines. The imbalance in cytokine production was also observed in ABT-263-treated IAV-infected mice, which resulted in an inability of the immune system to clear the virus and eventually lowered the survival rates of infected animals. Thus, the results suggest that the chemical inhibition of Bcl-xL, Bcl-2 and Bcl-w could potentially be hazardous for cancer patients with viral infections.

[The difference between rheumatoid factors and normal immunoglobulins disclosed by a monomolecular layer technic]. / Otlichie revmatoidnykh faktorov ot normal'nykh immunoglobulinov, obnaruzhennoe metodom monomolekuliarnykh sloev.

20 rheumatoid factors of two classes, namely IgG and IgM, were isolated from the serum of 11 patients with rheumatoid arthritis. The method of monolayer analysis revealed that these proteins differ from normal ones either by the instability of their native structure, or by their anomalous hydrophilic properties. Dialysis resulted in partial or complete restoration of normal properties in the majority of samples studied. It has been concluded that at least some of the rheumatoid factors are complex structures that contain, beside IgG and IgM molecules, also certain smaller molecules.

[Orientation and kinetics of surface denaturation of normal human and myeloma IgA in monolayers at the interface of air-NaCl aqueous solutions]. / Orientatsiia i kinetika poverkhnostnoi denaturatsii normal'nykh i mielomnykh IgA cheloveka v monomolekuliarnykh sloiakh na granitse faz vodnye rastvory NaCl-vozdukh.

Normal serum immunoglobulin A (IgA) and abnormal IgA isolated from serum of patients with multiple A-myeloma have been studied by monolayer technique at air--NaCl solution interfaces. Normal IgA analogous to human normal IgG and secretory IgA was shown to have horizontal orientation at air--water interface. Only some abnormal IgA were similar to myeloma IgG and differed from the normal ones by their orientation at phase border. Majority of myeloma IgA under study could not be distinguished from the normal ones by orientation and denaturation kinetics at interface. B-lymphocytes of the first group of patients were assumed to carry IgA-receptors at their surface, but B-lymphocytes of the second group of patients carried Ig receptors of some other class of immunoglobulins.