Use of alternate coreceptors on primary cells by two HIV-1 isolates

Tonie Cilliers, Samantha Willey, W Mathew Sullivan, Trudy Patience, Pavel Pugach, Mia Coetzer, Maria Papathanasopoulos, John P Moore, Alexandra Trkola, Paul Clapham, Lynn Morris

Research output: Contribution to journalArticlepeer-review

Abstract

Two HIV-1 isolates (CM4 and CM9) able to use alternate HIV-1 coreceptors on transfected cell lines were tested for their sensitivity to inhibitors of HIV-1 entry on primary cells. CM4 was able to use CCR5 and Bob/GPR15 efficiently in transfected cells. The R5 isolate grew in Delta32/Delta32 CCR5 PBMC in the absence or presence of AMD3100, a CXCR4-specific inhibitor, indicating that it uses a receptor other than CCR5 or CXCR4 on primary cells. It was insensitive to the CCR5 entry inhibitors RANTES and PRO140, but was partially inhibited by vMIP-1, a chemokine that binds CCR3, CCR8, GPR15 and CXCR6. The coreceptor used by this isolate on primary cells is currently unknown. CM9 used CCR5, CXCR4, Bob/GPR15, CXCR6, CCR3, and CCR8 on transfected cells and was able to replicate in the absence or presence of AMD3100 in Delta32/Delta32 CCR5 PBMC. It was insensitive to eotaxin, vMIP-1 and I309 when tested individually, but was inhibited completely when vMIP-1 or I309 was combined with AMD3100. Both I309 and vMIP-1 bind CCR8, strongly suggesting that this isolate can use CCR8 on primary cells. Collectively, these data suggest that some HIV-1 isolates can use alternate coreceptors on primary cells, which may have implications for strategies that aim to block viral entry.
Original languageEnglish
Pages (from-to)136-44
Number of pages9
JournalVirology
Volume339
Issue number1
DOIs
Publication statusPublished - 15 Aug 2005

Keywords

  • Adult
  • Amino Acid Sequence
  • Cell Line
  • Female
  • HIV Envelope Protein gp120
  • HIV Infections
  • HIV-1
  • Humans
  • Male
  • Molecular Sequence Data
  • Receptors, Chemokine
  • Receptors, HIV
  • Virus Replication

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