Isolation of primary HIV-1 that target CD8+ T lymphocytes using CD8 as a receptor.
HIV-1 use CD4 receptors to infect their primary targets, CD4+ cells, whereas CD8+ cells have a protective role against HIV-1. We recently isolated HIV-1-producing CD8+ clones from two AIDS patients. Here we show that although HIV-1 produced by CD8+ cells maintained the ability to infect CD4+ cells, these viruses were able to infect CD8+ cells independent of CD4. Evidence indicates that these viruses used CD8 as a receptor to infect CD8+ cells. First, expression of CD8 was downmodulated after infection. Second, anti-CD8 antibodies blocked viral entry and replication in CD8+ cells. Finally, resistant cells became susceptible after expression of CD8. Although these viruses used CXCR4 to enter CD4+ cells, it seems that infection of CD8+ cells was independent of CXCR4 or CCR5 co-receptors. Novel changes were observed in envelope sequences of CD8-tropic viruses. These results provide initial evidence that HIV-1 can mutate to infect CD8+ cells using CD8 as a receptor.
Saha
K
K
Division of Molecular Medicine, Department of Pediatrics, Children's Research Institute and The Ohio State University Medical Center, Columbus, Ohio 43205, USA. sahak@pediatrics.ohio-state.edu
Zhang
J
J
Gupta
A
A
Dave
R
R
Yimen
M
M
Zerhouni
B
B
D000595:Amino Acid Sequence; D001483:Base Sequence; D016827:CD8 Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D002460:Cell Line; D017931:DNA Primers; D015497:HIV-1 / Q000737:chemistry / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D016827:CD8 Antigens; D017931:DNA Primers; D011991:Receptors, Virus