The antiviral protein cyanovirin-N: the current state of its production and applications.

Human immunodeficiency virus (HIV)/AIDS continues to spread worldwide, and most of the HIV-infected people living in developing countries have little or no access to highly active antiretroviral therapy. The development of efficient and low-cost microbicides to prevent sexual transmission of HIV should be given high priority because there is no vaccine available yet. Cyanovirin-N (CVN) is an entry inhibitor of HIV and many other viruses, and it represents a new generation of microbicide that has specific and potent activity, a different mechanism of action, and unusual chemicophysical stability. In vitro and in vivo antiviral tests suggested that the anti-HIV effect of CVN is stronger than a well-known gp120-targeted antibody (2G12) and another microbicide candidate, PRO2000. CVN is a cyanobacteria-derived protein that has special structural features, making the artificial production of this protein very difficult. In order to develop an efficient and relatively low-cost approach for large-scale production of recombinant CVN to satisfy medical use, this protein has been expressed in many systems by trial and error. Here, to summarize the potential and remaining challenges for the development of this protein into an HIV prevention agent, the progress in the structural mechanism determination, heterologous production and pharmacological evaluation of CVN is reviewed

Macrophage Bactericidal Activities against <i>Staphylococcus aureus</i> Are Enhanced <i>In Vivo</i> by Selenium Supplementation in a Dose-Dependent Manner

<div><p>Background</p><p>Dietary selenium is of fundamental importance to maintain optimal immune function and enhance immunity during infection. To this end, we examined the effect of selenium on macrophage bactericidal activities against <i>Staphylococcus aureus</i>.</p><p>Methods</p><p>Assays were performed in golden Syrian hamsters and peritoneal macrophages cultured with <i>S</i>. <i>aureus</i> and different concentrations of selenium.</p><p>Results</p><p>Infected and selenium-supplemented animals have significantly decreased levels of serum nitric oxide (NO) production when compared with infected but non-selenium-supplemented animals at day 7 post-infection (<i>p</i> < 0.05). A low dose of 5 ng/mL selenium induced a significant decrease in macrophage NO production, but significant increase in hydrogen peroxide (H₂O₂) levels (respectively, <i>p</i> = 0.009, <i>p</i> < 0.001). The NO production and H₂O₂ levels were significantly increased with increasing concentrations of selenium; the optimal macrophage activity levels were reached at 20 ng/mL. The concentration of 5 ng/mL of selenium induced a significant decrease in the bacterial arginase activity but a significant increase in the macrophage arginase activity. The dose of 20 ng/mL selenium induced a significant decrease of bacterial growth (<i>p</i> < 0.0001) and a significant increase in macrophage phagocytic activity, NO production/arginase balance and <i>S</i>. <i>aureus</i> killing (for all comparisons, <i>p</i> < 0.001).</p><p>Conclusions</p><p>Selenium acts in a dose-dependent manner on macrophage activation, phagocytosis and bacterial killing suggesting that inadequate doses may cause a loss of macrophage bactericidal activities and that selenium supplementation could enhance the <i>in vivo</i> control of immune response to <i>S</i>. <i>aureus</i>.</p></div

Regulation of immune responses by L- arginine metabolism

L-Arginine is an essential amino acid for birds and young mammals, and it is a conditionally essential amino acid for adult mammals, as it is important in situations in which requirements exceed production, such as pregnancy. Recent findings indicate that increased metabolism of L-arginine by myeloid cells can result in the impairment of lymphocyte responses to antigen during immune responses and tumour growth. Two enzymes that compete for L-arginine as a substrate - arginase and nitric-oxide synthase - are crucial components of this lymphocyte-suppression pathway, and the metabolic products of these enzymes are important moderators of T-cell function. This Review article focuses on the relevance of L-arginine metabolism by myeloid cells for immunity under physiological and pathological conditions