Effects Of Human Interferon-alpha Research Articles

The effect of human interferon alpha on replication of different bovine viral diarrhea virus strains.

Bovine viral diarrhea virus (BVDV) exists in two main biotypes: cytopathic (cp) and noncytopathic (ncp). Although some studies were done on the effect of interferon alpha (IFN-α) on BVDV, the effect of exogenous IFN against BVDV biotypes remains unclear. In the present study, we evaluated the comparative effect of exogenous human IFN-α (HuIFN-α) on different BVDV biotypes and genotypes. The results showed that exogenous HuIFN-α greatly inhibited the growth of different BVDV biotypes and genotypes. However, HuINF-α has a significant inhibitory effect on cp biotype compared to ncp one without significant variation between different genotypes. The effect of HuIFN-α on BVDV reached the maximum level at early stages of infection (0-20 h post infection) and increased in a dose-dependent manner (10-500 U/ml). Quantitative real-time RT-PCR was used to evaluate the effect of exogenous HuIFN-α on RNA synthesis of both BVDV biotypes. HuIFN-α reduced RNA production of cp by 4 logs compared to only 2 logs for ncp strains. Additionally, the antiviral effect of IFN-α against both BVDV biotypes seems to be independent of the RNA-dependent protein kinase (PKR) activation as assayed by direct analysis of in vivo phosphorylation of eIF2-α and by 2-aminopurine (2-AP) treatment. Collectively, these results indicated that the exogenous HuIFN-α treatment has an inhibitory effect not only on cp BVDV biotype but also on the ncp BVDV. The antiviral effect of exogenous HuIFN-α was biotype, time, dose but not genotype dependent. PKR has no role in the inhibitory effect suggesting that other IFN-antiviral pathways were involved. Keywords: BVDV biotypes; HuIFN-α; RNA synthesis; PKR-independent.

Immune aspects of embryo-maternal cross-talk in the bovine uterus

This mini-review summarizes the results of recent transcriptome studies of bovine endometrium during the estrous cycle and during the pre-implantation phase, with a focus on immune response genes. Gene expression changes in the bovine endometrium during the estrous cycle were compared to a similar study in equine endometrium. The results indicate species-specific expression patterns, particularly for genes with immune functions. These are presumably the consequence of adaptations to differences in the physiology of reproduction in each species, including development of the conceptus, hormone profiles during the estrous cycle, and insemination. The results from a number of transcriptome studies during the pre-implantation phase, as well as comparison to the effects of human interferon alpha on bovine endometrial gene expression, suggest that during pregnancy there is no general suppression of the maternal immune system, but rather a fine-tuned regulation of immune cells. This presumably facilitates tolerance to the immunologically ‘foreign’ conceptus and at the same time activation of the immune system to defend against microbial and viral infections. Furthermore, comparison of differentially expressed genes in bovine endometrium to similar studies in human endometrial samples reveals a number of similar changes, indicating the existence of shared mechanisms in preparation for embryo implantation.

Obstruction of HIV-1 Particle Release by Interferon-α Occurs Before Viral Protease Processing and Is Independent of Envelope Glycoprotein

The effect of human interferon-alpha (Hu-IFN-alpha) on the maturation process of the human immunodeficiency virus type 1 (HIV-1) has been studied using stable cell lines that produce nonenveloped particles. These cell lines secrete particles devoid of the viral envelope proteins gp120 and gp41. The CH-1 cells produce active viral protease that correctly processes its natural substrates, whereas the CH-1kww cell line expresses an enzymatically inactive viral protease, thus producing immature viral capsids. A block in the secretion of particles was observed in both cell lines when treated with 100-1000 U/ml Hu-IFN-alpha, as judged by measurements of encapsidated gag proteins. Electron microscopy shows that Hu-IFN-alpha-treated CH-1 cells are decorated with assembled immature particles at the cell surface. These results suggest that the observed block in particle release on Hu-IFN-alpha treatment is independent of viral envelope expression and occurs before capsid polyprotein processing. In addition, particles remaining attached to the cell fail to mature into structures with condensed cores. Viral gag proteins from IFN-treated and untreated CH-1 cells were analyzed by 2-D gel electrophoresis. Results suggest a change in posttranslational modifications of gag proteins, as IFN treatment allowed the detection of more basic forms of p55, p39, and p24. Further analysis of cellular or viral protein alterations induced by Hu-IFN-alpha treatment may identify the mechanism of action by which particle maturation is obstructed.

Effects of Interferon-α on a Reduced Release of Interleukin-8 from Latently HIV-1-Infected Monocytic Cell Line U937 Cells

The effects of human interferon-alpha (IFN-alpha) on the release of an antimicrobial interleukin, interleukin-8 (IL-8), from human immunodeficiency virus type 1 (HIV-1)-infected myelomonocytic cell line, U937, were studied in vitro to evaluate the potential of IFN-alpha in the management of acquired immunodeficiency syndrome (AIDS)-associated opportunistic diseases. The latently HIV-1-infected U937 cells (U937/HIV-1(L)) showed a marked reduction of IL-8 secretion as compared to uninfected U937 cells, whereas IL-8 release from productively HIV-1-infected U937 cells was comparable to uninfected cells. The IFN-alpha recovered partially the reduced IL-8 level from U937/HIV-1(L) cells in a dose-dependent manner. Any significant inhibition of IFN-alpha-augmented IL-8 secrement by anti-IL-1 antibody was not observed, suggesting that the enhanced IL-8 secretion occurred without augmenting IL-1 production. The IFN-alpha-augmented IL-8 secretion from latently HIV-1-infected U937 cells may suggest a beneficial potential of IFN-alpha in a treatment of bacterial or fungal infection frequently seen in patients with progressive stages of HIV-1 infection.

Effect of toremifene on the activity of NK-cells in NZB/NZW mice

The effect of toremifene on NK-cells isolated from the spleen of NZB/NZW mice was studied in comparison to tamoxifen and estradiol. Unlike estradiol but like tamoxifen, toremifene did not influence the activity of NK-cells. Low doses (0.1 and 10.0 mg/kg) of toremifene did not suppress, but a high dose of toremifene and tamoxifen (50 mg/kg for 6 weeks) suppressed the stimulating effect of human interferon alpha on the cells.

The effects of human interferon-alpha upon in vitro canine immune responses

The effects of varying amounts (100.0-0.01 units/ml) of human interferon (IFN) alpha upon in vitro canine immune responses were studied. Exogenous heterologous species IFN-alpha suppressed B-cell differentiation in a dose-dependent fashion and enhanced interleukin-2 production ( P < 0.05) by activated T-lymphocytes. Interferon enhanced natural killer (NK) cytotoxicity when tested against NK-resistant target cells (< 0.05). One hundred units IFN/ml increased interleukin-1 production by canine monocytes, but this effect was not statistically significant. Exogenous IFN had no discernible effect upon lectin-induced lymphocyte blastogenesis. The results of this study demonstrate that human IFN-alpha does affect various canine lymphocyte functions and these effects depend upon the in vitro assay system employed.

Presence of an abnormal beta 2-microglobulin mRNA in Daudi cells: induction by interferon.

Human alpha and beta interferons increase the amount of class I human histocompatibility messenger RNA HLA-A, B, C and beta 2-microglobulin in most human cells studied to date. This report concerns the effect of interferons on the Burkitt lymphoma-derived cell line Daudi, which does not express HLA-A, B, C antigens or beta 2-microglobulin on its membrane. HLA-A, B, C messenger RNA present in Daudi cells is increased by both alpha and beta interferons. Furthermore, we have shown that although it was not possible to detect mature beta 2-microglobulin protein in the cytoplasm or on the cell membrane of Daudi cells, a poly A+ messenger RNA is present in Daudi cells, which hybridizes with a cDNA clone specific for human beta 2-microglobulin. This abnormal messenger RNA is, however, increased normally by interferon. These effects were also observed with human interferon beta on a variant of Daudi cells characterized by a markedly reduced sensitivity to anti-proliferative and anti-cellular effects of human interferon alpha.

Interferon inhibits the generation of allospecific suppressor T lymphocytes.

The effect of human interferon alpha on the differentiation of functional populations of lymphocytes during the human allogeneic response in vitro was studied. Interferon alpha inhibited the generation of allospecific suppressor T lymphocytes that normally develop from lymphocytes primed in vitro against allogeneic cells. This effect was not the result of the destruction by interferon of precursor suppressor cells but rather to inhibition of their differentiation into active suppressor T lymphocytes. This inhibition was reversible and could be overcome by repeated allogeneic stimulation even in the presence of interferon. Inhibition of the generation of allospecific suppressor lymphocytes by interferon might play an important role in the allogeneic response. Interferon inhibited the proliferation of lymphocytes after allogeneic stimulation in a primary mixed lymphocyte reaction but enhanced their cytotoxicity. Despite the inhibitory effect in the primary mixed lymphocyte reaction, the specific secondary proliferative response of lymphocytes primed against a single HLA-DR antigen was only slightly affected by interferon. On the other hand, the nonspecific secondary proliferative response of lymphocytes primed in the presence of interferon was significantly reduced, indicating that interferon might decrease the recruitment of nonspecific "irrelevant" clones of responding cells during the sensitization period.