Lack of alternative coreceptor use by pediatric HIV-1 R5 isolates for infection of primary cord or adult peripheral blood mononuclear cells.
HIV-1 infection of neonates results in an extended acute period of virus replication, frequent neurological problems and reduced survival compared to adults. In adults, R5 viruses mainly infect CCR5(+) CD4(+) memory T-cells. In neonates, CCR5(+) memory T-cells form a substantially smaller fraction of total lymphocytes. We therefore tested whether alternative coreceptors confer infection of lymphocytes by pediatric isolates. Pediatric HIV-1 R5 isolates failed to replicate in Delta32/Delta32 CCR5 PBMCs or in cord PBMCs treated with a CCR5 inhibitor. These results do not indicate a role for alternative coreceptors and provide support for CCR5 inhibitors in the therapy of HIV-1(+) neonates.
Sullivan
W M
WM
Center for AIDS Research, Program in Molecular Medicine and Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Dorr
P
P
Perros
M
M
Hudson
R
R
Leif
J
J
Luzuriaga
K
K
Clapham
P R
PR
D065100:CCR5 Receptor Antagonists; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000821:virology*; D019713:Receptors, CCR5 / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology*; D053586:Virus Internalization; D014779:Virus Replication / Q000502:physiology*
D065100:CCR5 Receptor Antagonists; D019713:Receptors, CCR5; D011991:Receptors, Virus; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase