[Requirements for the Induction of Broadly Neutralizing Antibodies against HIV-1 by Vaccination].

A study of the induction of broadly neutralizing antibodies (bNAbs) in HIV-infected patients and vaccinated subjects revealed the main criteria for the formation of bNAbs (the duration of exposure to a viral antigen, the effect of the diversity of HIV variants, and the removal of barriers associated with the Env-dependent defense mechanisms of HIV-1). Modified trimers of the HIV-1 envelope protein (Env) exposed on virus-like particles (VLP) have unique properties: they (i) modulate the exposure of binding sites (bs) of the CD4 receptor and co-receptor; (ii) create steric restrictions for contact with bNAbs; (iii) increase the Env presentation density, thus enhancing the immune response; (iv) form stable trimers that do not induce off-target immune responses; and (v) allow additional modifications to their structure and construction of a platform with immunostimulating molecules. Immunization using a heterologous subtype-cross prime-boost regime with modified trimeric Env is capable of inducing somatic hypermutation levels necessary for the formation of bNAbs.

Enhanced expression of trim14 gene suppressed Sindbis virus reproduction and modulated the transcription of a large number of genes of innate immunity.

In the present research, we have studied an influence of enhanced expression TRIM14 on alphavirus Sindbis (SINV, Togaviridae family) infection. In the HEK293 cells transfected with human trim14 gene (HEK-trim14), SINV yield after infection was decreased 1000-10,000 times (3-4 lg of TCD50/ml) at 24 h p.i.

Contamination of cell cultures with bovine viral diarrhea virus (BVDV).

The incidence of contamination of cell strains used in biological and virological studies and of fetal calf sera (FCS) manufactured by Russian and foreign companies used for cell culturing with noncytocidal bovine viral diarrhea virus (BVDV; Pestivirus, Flaviviridae) was analyzed. The virus was detected by reverse transcription PCR and indirect immunofluorescence with monoclonal antibodies to BVDV virion envelope glycoprotein in 25% of 117 cell strains and 45% of 35 tested FCS lots. The virus multiplied and persisted in a wide spectrum of human cell strains and in monkey, swine, sheep, rabbit, dog, cat, and other animal cells.

[CMV-induced cell death and fas gene expression in resting and proliferating human fibroblasts].

Cytomegalovirus (CMV) infection development and mRNA fas transcription levels (CD95) in resting (GO) and proliferating (S-phase) human lung embryo fibroblasts (HLEF-110044 line) were studied. In GO cells accumulation of infectious CMV was high and cell death was very quick, and fas gene expression was inhibited in early period of infection. In cells infected during S-phase CMV synthesis was lower and total cell death was detected only after 5 days; fas gene activity remained on high levels and increased during 6-48 hours.

[Regulation of human fibrolastic 2',5'-oligoadenylate synthetase gene activity in cytomegalovirus infected fibroblast cells].

Great differences were found in the level of 2',5'-oligoadenylate synthetase 40-46 kDa (OAS1) mRNA in relation to the proliferative state of human diploid fibroblasts at the moment of cytomegalovirus (CMV) (the strain AD169) infection. In the phase of synthesis of cellular cycle DNA (S), CMV induced OAS1 mRNA transcription by 10-100 times stronger than then in phase Go infection. The level of viral induction OAS1 mRNA peaked by hour 12 postinfection.