Use of alternate coreceptors on primary cells by two HIV-1 isolates.
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.
AIDS Virus Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, South Africa.
Tonie
T
Cilliers
Samantha
S
Willey
W Mathew
WM
Sullivan
Trudy
T
Patience
Pavel
P
Pugach
Mia
M
Coetzer
Maria
M
Papathanasopoulos
John P
JP
Moore
Alexandra
A
Trkola
Paul
P
Clapham
Lynn
L
Morris
D000328:Adult; D000595:Amino Acid Sequence; D002460:Cell Line; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D019707:Receptors, Chemokine / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism*; D014779:Virus Replication
D015699:HIV Envelope Protein gp120; D019707:Receptors, Chemokine; D015728:Receptors, HIV