Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals: association with low expression of CCR5 and high production of beta-chemokines.
We examined the human immunodeficiency virus type 1 infectability of CD4+ lymphocytes isolated from CCR5 wild-type individuals, individuals heterozygous for the delta32 allele of CCR5, and HIV-1-exposed but uninfected (EU) individuals who had CD4+ lymphocytes refractory to M-tropic viral replication. None of the EU individuals were found to be heterozygous for the delta32 allele. The CD4+ lymphocytes isolated from CCR5/delta32 and EU individuals were less infectable with an M-tropic viral isolate of HIV-1 than CCR5/CCR5 control individuals but were equally as infectable with a T-tropic viral isolate. The restriction to M-tropic viral isolate replication did not associate with any profound genotypic change in the CCR5 gene. CD4+ lymphocytes from CCR5/delta32 and CCR5/CCR5 EU individuals were more sensitive to the HIV-inhibitory effects of the recombinant beta-chemokines RANTES, MIP-1alpha, and MIP-1beta than were CD4+ lymphocytes from CCR5/CCR5 control individuals. CD4+ lymphocytes from EU individuals also showed increased sensitivity to recombinant beta-chemokines and low surface expression of CCR5. A phenotype of low CCR5 expression and high secretion of beta-chemokines is associated with reduced infectability of cells by M-tropic HIV-1. This phenotype may also be associated with protection against sexual transmission of HIV-1.
Paxton
W A
WA
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
Liu
R
R
Kang
S
S
Wu
L
L
Gingeras
T R
TR
Landau
N R
NR
Mackay
C R
CR
Koup
R A
RA
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D005838:Genotype; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology
D018946:Chemokine CCL5; D018925:Chemokines; D019713:Receptors, CCR5; D011994:Recombinant Proteins