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.
Cilliers
Tonie
T
AIDS Virus Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, South Africa.
Willey
Samantha
S
Sullivan
W Mathew
WM
Patience
Trudy
T
Pugach
Pavel
P
Coetzer
Mia
M
Papathanasopoulos
Maria
M
Moore
John P
JP
Trkola
Alexandra
A
Clapham
Paul
P
Morris
Lynn
L
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