Anti-HIV Effects of Chloroquine: Inhibition of Viral Particle Glycosylation and Synergism with Protease Inhibitors

Andrea Savarino, Mothanje B. Lucia, Elena Rastrelli, Sergio Rutella, Caterina Golotta, Emanuella Morra, Enrica Tamburrini, Carlo Federico Perno, Johan R. Boelaert, Kirk Sperber, Roberto Cauda

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Objective: We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1). Design: CD4+ cell lines were infected with laboratory strains and peripheral blood mononuclear cells were infected with primary isolates for evaluation of the anti-HIV effects. Peripheral blood lymphocytes were evaluated for of P-gp and MRP1 functions. Methods: HIV replication was assessed by enzyme-linked immunosorbent assay. HIV glycosylation was measured by metabolic labeling of viral particles with [3H] glucosamine. Synergism was tested using isobolograms. P-gp and MRP1 functions were assayed using rhodamine 123 (Rh123) and carboxyfluorescein (CF) efflux assays, respectively. Results: CQ alone inhibited HIV replication and glycosylation in a dose-dependent manner. In combination with indinavir (IDV), ritonavir, or saquinavir (SQV), CQ had a synergistic effect at concentrations found in plasma of subjects receiving malaria prophylaxis. CQ decreased the 50% effective concentration of IDV in primary isolates from Africa and restored the response to IDV or SQV in 3 PI-resistant isolates. CQ increased the block of Rh123 and CF efflux activity exerted by PIs. Conclusion: The inhibitory effects of CQ on HIV glycosylation are associated with synergistic effects in combination with PIs. The CQ/PI combination exerts combined inhibitory effects on P-gp and MRP1 function.

Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume35
Issue number3
DOIs
Publication statusPublished - Mar 1 2004

Fingerprint

Chloroquine
P-Glycoprotein
Protease Inhibitors
Glycosylation
Virion
HIV
Indinavir
Saquinavir
Rhodamine 123
HIV Protease Inhibitors
Ritonavir
Glucosamine
Malaria
Blood Cells
Enzyme-Linked Immunosorbent Assay
Lymphocytes
Cell Line

Keywords

  • Antimalarial
  • Developing countries
  • Multidrug resistance protein-1
  • P-glycoprotein
  • Protease inhibitors
  • Synergism

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Anti-HIV Effects of Chloroquine : Inhibition of Viral Particle Glycosylation and Synergism with Protease Inhibitors. / Savarino, Andrea; Lucia, Mothanje B.; Rastrelli, Elena; Rutella, Sergio; Golotta, Caterina; Morra, Emanuella; Tamburrini, Enrica; Perno, Carlo Federico; Boelaert, Johan R.; Sperber, Kirk; Cauda, Roberto.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 35, No. 3, 01.03.2004, p. 223-232.

Research output: Contribution to journalArticle

Savarino, A, Lucia, MB, Rastrelli, E, Rutella, S, Golotta, C, Morra, E, Tamburrini, E, Perno, CF, Boelaert, JR, Sperber, K & Cauda, R 2004, 'Anti-HIV Effects of Chloroquine: Inhibition of Viral Particle Glycosylation and Synergism with Protease Inhibitors', Journal of Acquired Immune Deficiency Syndromes, vol. 35, no. 3, pp. 223-232. https://doi.org/10.1097/00126334-200403010-00002
Savarino, Andrea ; Lucia, Mothanje B. ; Rastrelli, Elena ; Rutella, Sergio ; Golotta, Caterina ; Morra, Emanuella ; Tamburrini, Enrica ; Perno, Carlo Federico ; Boelaert, Johan R. ; Sperber, Kirk ; Cauda, Roberto. / Anti-HIV Effects of Chloroquine : Inhibition of Viral Particle Glycosylation and Synergism with Protease Inhibitors. In: Journal of Acquired Immune Deficiency Syndromes. 2004 ; Vol. 35, No. 3. pp. 223-232.
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abstract = "Objective: We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1). Design: CD4+ cell lines were infected with laboratory strains and peripheral blood mononuclear cells were infected with primary isolates for evaluation of the anti-HIV effects. Peripheral blood lymphocytes were evaluated for of P-gp and MRP1 functions. Methods: HIV replication was assessed by enzyme-linked immunosorbent assay. HIV glycosylation was measured by metabolic labeling of viral particles with [3H] glucosamine. Synergism was tested using isobolograms. P-gp and MRP1 functions were assayed using rhodamine 123 (Rh123) and carboxyfluorescein (CF) efflux assays, respectively. Results: CQ alone inhibited HIV replication and glycosylation in a dose-dependent manner. In combination with indinavir (IDV), ritonavir, or saquinavir (SQV), CQ had a synergistic effect at concentrations found in plasma of subjects receiving malaria prophylaxis. CQ decreased the 50{\%} effective concentration of IDV in primary isolates from Africa and restored the response to IDV or SQV in 3 PI-resistant isolates. CQ increased the block of Rh123 and CF efflux activity exerted by PIs. Conclusion: The inhibitory effects of CQ on HIV glycosylation are associated with synergistic effects in combination with PIs. The CQ/PI combination exerts combined inhibitory effects on P-gp and MRP1 function.",
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AU - Lucia, Mothanje B.

AU - Rastrelli, Elena

AU - Rutella, Sergio

AU - Golotta, Caterina

AU - Morra, Emanuella

AU - Tamburrini, Enrica

AU - Perno, Carlo Federico

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