Coevolution Analysis of HIV-1 Envelope Glycoprotein Complex

The HIV-1 Env spike is the main protein complex that facilitates HIV-1 entry into CD4⁺ host cells. HIV-1 entry is a multistep process that is not yet completely understood. This process involves several protein-protein interactions between HIV-1 Env and a variety of host cell receptors along with many conformational changes within the spike. HIV-1 Env developed due to high mutation rates and plasticity escape strategies from immense immune pressure and entry inhibitors. We applied a coevolution and residue-residue contact detecting method to identify coevolution patterns within HIV-1 Env protein sequences representing all group M subtypes. We identified 424 coevolving residue pairs within HIV-1 Env. The majority of predicted pairs are residue-residue contacts and are proximal in 3D structure. Furthermore, many of the detected pairs have functional implications due to contributions in either CD4 or coreceptor binding, or variable loop, gp120-gp41, and interdomain interactions. This study provides a new dimension of information in HIV research. The identified residue couplings may not only be important in assisting gp120 and gp41 coordinate structure prediction, but also in designing new and effective entry inhibitors that incorporate mutation patterns of HIV-1 Env.     

Phenolic content and antioxidant activity in two contrasting Medicago ciliaris lines cultivated under salt stress

The objective of this study was to determine more indepth physiological and antioxidant responses in two Medicago ciliaris lines (a salt-tolerant line TNC 1.8 and a salt-sensitive line TNC 11.9) with contrasting responses to 100 mM NaCl. Under salt stress, both lines showed a decrease in total biomass and in the growth rate for roots, but TNC 1.8 was less affected by salt than TNC 11.9 in that it maintained leaf growth even in the presence of added salt. In both lines, salt stress mainly affected micronutrient status (Fe, Mn, Cu and Zn) rather than K nutrition, but the tolerant line TNC 1.8 accumulated more Na in leaves and less in roots compared with TNC 11.9. Salt stress decreased total soluble sugars (TSS) in all organs of the sensitive line TNC 11.9, whereas TSS was only reduced in roots of the tolerant line. The salt-induced drop in growth was linked to an increase in lipid peroxidation in roots of both lines and in leaves of the sensitive line. The salt-tolerant line TNC 1.8 was more efficient at managing salt-induced oxidative damage in leaves and to a lesser extent in roots than the salt-sensitive line TNC 11.9, by preserving higher phenolic compound and superoxide dismutase levels in both organs.     

Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C

Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world.     

Salt stress (NaCl) affects plant growth and branch pathways of carotenoid and flavonoid biosyntheses in <Emphasis Type="Italic">Solanum nigrum</Emphasis>

In this study, we set out to investigate the effect of sodium chloride (NaCl) on carotenoid and flavonoid production by the black nightshade (Solanum nigrum L.). The study was carried out under green chamber conditions using seedlings subjected to 0, 50, 100 and 150 mM NaCl for 3 weeks. The negative effect of NaCl on dry biomass production of roots and leaves were accompanied by a significant restriction in K⁺, Ca²⁺ and Mg²⁺ ion uptake and by an increase in Na⁺ ion concentrations, the effects of which were most pronounced at the highest NaCl level. Salt stress also induced oxidative stress, according to the amplified levels of thiobarbituric acid reactive substances and relative ion leakage ratio. Expression of some related carotenoid (phytoene synthase 2 and β-lycopene cyclase) and flavonoids genes (phenylalanine ammonialyase, chalcone synthase and flavonol synthase) were induced by NaCl, followed enhanced production of β-carotene, lutein, and quercetin 3-β-d-glucoside. At the highest NaCl level (150 mM NaCl), quercetin 3-β-d-glucoside synthesis came at the expense of reduced β-carotene and lutein, while salt stress treatment affected leaf antioxidant activities to a great extent relative to the control. Our data suggest that the potential antioxidant properties of carotenoids and flavonoids and their related key genes may be efficiently involved in the restriction of salt-induced oxidative damages.