Entry inhibitors SCH-C, RANTES, and T-20 block HIV type 1 replication in multiple cell types.
The small-molecule CCR5 antagonist SCH-C (SCH 351125) was tested for its ability to inhibit HIV-1 replication in peripheral blood mononuclear cells (PBMCs), cord blood mononuclear cells, immature dendritic cells (DCs), and macrophages. Inhibition of infection of PBMCs by virus associated with mature DC in trans was also studied. For comparison, the peptide-based fusion inhibitor T-20 and the CC-chemokine RANTES were also evaluated. Although some cell type-dependent differences in potency were observed, each of the three entry inhibitors was active against the replication of three different CCR5-using primary isolates in each cell type. CCR5-dependent HIV-1 infectivity, whether DC associated or not, is thus vulnerable to inhibitors that block the virus-cell fusion process by different mechanisms. Together, these results suggest that SCH-C and other entry inhibitors should be evaluated for their clinical potential as inhibitors of HIV-1 replication in several settings, including the prevention of maternal-infant transmission and the prevention of sexual transmission by topical application as a microbicide.
Ketas
Thomas J
TJ
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Klasse
Per Johan
PJ
Spenlehauer
Catherine
C
Nesin
Mirjana
M
Frank
Ines
I
Pope
Melissa
M
Strizki
Julie M
JM
Reyes
Gregory R
GR
Baroudy
Bahige M
BM
Moore
John P
JP
D019380:Anti-HIV Agents / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D002451:Cell Compartmentation; D018946:Chemokine CCL5 / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003713:Dendritic Cells / Q000821:virology; D004347:Drug Interactions; D000077560:Enfuvirtide; D005312:Fetal Blood / Q000821:virology; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology; D010091:Oximes; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines; D011725:Pyridines / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5; D003497:Cyclic N-Oxides; D015700:HIV Envelope Protein gp41; D010091:Oximes; D010446:Peptide Fragments; D010880:Piperidines; D011725:Pyridines; D019713:Receptors, CCR5; D000077560:Enfuvirtide; C438583:Ancriviroc