GM-3 Lactone Mimetic Interacts with CD4 and HIV-1 Env Proteins, Hampering HIV-1 Infection without Inducing a Histopathological Alteration

Barbara Richichi, Claudia Pastori, Stefano Gherardi, Assunta Venuti, Antonella Cerreto, Francesca Sanvito, Lucio Toma, Lucia Lopalco, Cristina Nativi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)564-571
Number of pages8
JournalACS Infectious Diseases
Volume2
Issue number8
DOIs
Publication statusPublished - Aug 12 2016

Fingerprint

env Gene Products
Glycosphingolipids
Lactones
HIV Infections
HIV-1
Virus Internalization
CD4 Antigens
Gangliosides
Ovalbumin
Lipids
Antibodies
Infection
Proteins

Keywords

  • gangliosides
  • glycosides
  • HIV infection
  • mimetics

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

GM-3 Lactone Mimetic Interacts with CD4 and HIV-1 Env Proteins, Hampering HIV-1 Infection without Inducing a Histopathological Alteration. / Richichi, Barbara; Pastori, Claudia; Gherardi, Stefano; Venuti, Assunta; Cerreto, Antonella; Sanvito, Francesca; Toma, Lucio; Lopalco, Lucia; Nativi, Cristina.

In: ACS Infectious Diseases, Vol. 2, No. 8, 12.08.2016, p. 564-571.

Research output: Contribution to journalArticle

Richichi, Barbara ; Pastori, Claudia ; Gherardi, Stefano ; Venuti, Assunta ; Cerreto, Antonella ; Sanvito, Francesca ; Toma, Lucio ; Lopalco, Lucia ; Nativi, Cristina. / GM-3 Lactone Mimetic Interacts with CD4 and HIV-1 Env Proteins, Hampering HIV-1 Infection without Inducing a Histopathological Alteration. In: ACS Infectious Diseases. 2016 ; Vol. 2, No. 8. pp. 564-571.
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