ABSTRACT
Water-soluble sulfated polysaccharides isolated from two red algae Sphaerococcus coronopifolius (Gigartinales, Sphaerococcaceae) and Boergeseniella thuyoides (Ceramiales, Rhodomelaceae) collected on the coast of Morocco inhibited in vitro replication of the Human Immunodeficiency Virus (HIV) at 12.5 µg/mL. In addition, polysaccharides were capable of inhibiting the in vitro replication of Herpes simplex virus type 1 (HSV-1) on Vero cells values of EC50 of 4.1 and 17.2 µg/mL, respectively. The adsorption step of HSV-1 to the host cell seems to be the specific target for polysaccharide action. While for HIV-1, these results suggest a direct inhibitory effect on HIV-1 replication by controlling the appearance of the new generations of virus and potential virucidal effect. The polysaccharides from S. coronopifolius (PSC) and B. thuyoides (PBT) were composed of galactose, 3,6-anhydrogalactose, uronics acids, sulfate in ratios of 33.1, 11.0, 7.7 and 24.0% (w/w) and 25.4, 16.0, 3.2, 7.6% (w/w), respectively.
Subject(s)
Antiviral Agents/pharmacology , Polysaccharides/pharmacology , Rhodophyta/chemistry , Adsorption/drug effects , Animals , Antiviral Agents/analysis , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , Cell Survival , Chlorocebus aethiops , Galactose/analogs & derivatives , Galactose/chemistry , Galactose/pharmacology , HIV-1/drug effects , Herpesvirus 1, Human/drug effects , Humans , Matrix Metalloproteinase 17/drug effects , Molecular Weight , Morocco , Oceans and Seas , Phytotherapy , Plant Preparations/pharmacology , Polysaccharides/analysis , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Sulfates/chemistry , Sulfates/pharmacology , Time Factors , Uronic Acids/chemistry , Uronic Acids/pharmacology , Vero Cells , Virus Replication/drug effectsABSTRACT
The construction of a recombinant antibody directed against the cellular epitope R7V acquired by HIV during the viral budding has been realized. The c-DNAs encoding the variable regions of the anti-R7V antibody have been cloned from B lymphocytes of a non-progressor patient. Two transfer vectors containing complete coding sequences for heavy and light chains of this antibody were constructed and a recombinant baculovirus was generated by a double recombination between baculovirus DNA and the two transfer vectors. Insect cells infected with this baculovirus produced a complete human anti-R7V immunoglobulin. This recombinant antibody, specific to the R7V peptide, recognizes and neutralizes all clades of HIV1 including resistant viruses, opening new perspectives in anti-HIV therapy.
Subject(s)
Antibodies, Monoclonal/therapeutic use , HIV Antibodies/therapeutic use , HIV Infections/therapy , beta 2-Microglobulin/immunology , Amino Acid Sequence , Animals , Antiretroviral Therapy, Highly Active , Baculoviridae/genetics , Base Sequence , Cell Line , HIV-1/immunology , Humans , Molecular Sequence Data , Neutralization Tests , Recombinant Proteins/biosynthesis , Recombinant Proteins/therapeutic use , Spodoptera , Treatment FailureABSTRACT
Many attempts to use therapeutic antibodies to treat HIV have been unsuccessful owing to the high variability of the viral proteins, the multiplicity of the cellular targets, and the conformational changes of the gp120 glycoprotein during cell binding. A new concept of identifying a cellular antigen associated with the HIV envelope was investigated. The characterized epitope, R7V, is responsible for the formation of antibodies protective against HIV in non-progressor patients. The purified anti-R7V antibodies neutralize all HIV isolates, including the escape mutants after highly active antiretroviral therapy, creating a new therapeutic tool for the treatment of HIV-infected patients.
