Genetic and functional analysis of R5X4 human immunodeficiency virus type 1 envelope glycoproteins derived from two individuals homozygous for the CCR5delta32 allele.
We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) isolated from two HIV-1-infected CCR5delta32 homozygotes. Envs from both subjects used CCR5 and CXCR4 for entry into transfected cells. Most R5X4 Envs were lymphocyte-tropic and used CXCR4 exclusively for entry into peripheral blood mononuclear cells (PBMC), but a subset was dually lymphocyte- and macrophage-tropic and used either CCR5 or CXCR4 for entry into PBMC and monocyte-derived macrophages. The persistence of CCR5-using HIV-1 in two CCR5delta32 homozygotes suggests the conserved CCR5 binding domain of Env is highly stable and provides new mechanistic insights important for HIV-1 transmission and persistence.
Gray
Lachlan
L
Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne 3001, Victoria, Australia.
Churchill
Melissa J
MJ
Keane
Niamh
N
Sterjovski
Jasminka
J
Ellett
Anne M
AM
Purcell
Damian F J
DF
Poumbourios
Pantelis
P
Kol
Chenda
C
Wang
Bin
B
Saksena
Nitin K
NK
Wesselingh
Steven L
SL
Price
Patricia
P
French
Martyn
M
Gabuzda
Dana
D
Gorry
Paul R
PR
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D015497:HIV-1 / Q000502:physiology*; D006720:Homozygote; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D015686:Gene Products, env; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D008156:Luciferases