GM-3 Lactone Mimetic Interacts with CD4 and HIV-1 Env Proteins, Hampering HIV-1 Infection without Inducing a Histopathological Alteration.
Glycosphingolipids (GSLs) are involved in HIV-1 entry. GM-3 ganglioside, a widespread GSL, affects HIV entry and infection in different ways, depending on the concentration, through its anchoring activity in lipid rafts. This explains why the induction of an altered GSLs metabolism was a tempting approach to reducing HIV-1 cell infection. This study assayed the biological properties of a synthetic GM-3 lactone mimetic, 1, aimed at blocking HIV-1 infection without inducing the adverse events expected by an altered metabolism of GLSs in vivo. The mimetic, conjugated to immunogenic protein ovalbumin and multivalently presented, was able to bind the CD4 molecule with high affinity and block its engagement with gp120, thus inhibiting virus entry. Elicited antimimetic antibodies were also able to block HIV-1 infection in vitro, with activity complementary to that observed for 1. These preliminary results show that the use of GSLs mimetics can be a novel promising mode to block HIV-1 infection and that 1 and other GSL mimetics deserve further attention.
Department of Chemistry, University of Florence , 50019 Sesto F.no (FI), Italy.
Barbara
B
Richichi
Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20127 Milan, Italy.
Claudia
C
Pastori
Department of Chemistry, University of Florence , 50019 Sesto F.no (FI), Italy.
Stefano
S
Gherardi
Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20127 Milan, Italy.
Assunta
A
Venuti
Department of Chemistry, University of Florence , 50019 Sesto F.no (FI), Italy.
Antonella
A
Cerreto
Pathology Department, Mouse Histopathology Unit, San Raffaele Scientific Institute , 20100 Milan, Italy.
Francesca
F
Sanvito
Department of Chemistry, University of Pavia , Pavia, Italy.
Lucio
L
Toma
Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute , 20127 Milan, Italy.
Lucia
L
Lopalco
Department of Chemistry, University of Florence , 50019 Sesto F.no (FI), Italy.
Cristina
C
Nativi
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015704:CD4 Antigens / Q000737:chemistry* / Q000378:metabolism; D005732:Gangliosides / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D005732:Gangliosides; D015699:HIV Envelope Protein gp120; D007783:Lactones
HIV infection; gangliosides; glycosides; mimetics