Cellular tropisms and co-receptor usage of HIV-1 isolates from vertically infected children with neurological abnormalities and rapid disease progression.
The longitudinal evolution of HIV-1 phenotypes was studied in a cohort of six vertically infected children with early onset and rapid progression of clinical disease. Among 30 viral isolates obtained from peripheral blood, tropisms for both human blood-derived cells (macrophages, T-lymphocytes), and for human neural (brain-derived) cells (microglia, astrocytes) were determined, as was chemokine co-receptor usage. All children harbored from birth macrophage-tropic isolates using the CCR5 co-receptor. Two children later developed T-cell tropic isolates with CXCR4 and CCR3 usage. While all six patients developed neurological abnormalities, only three produced neural cell tropic isolates, which used CCR5. However, early and persistent finding of both astrocyte- and microglia-tropic isolates in one patient did associate with the most rapid progression to brain atrophy among the six patients. Viral phenotypic properties determined in cell culture did not specifically predict clinical features or course, and the development of AIDS did not coincide with, or depend on, the appearance T-tropic, syncytia-inducing viruses.
McCarthy
Micheline
M
Department of Veterans Affairs Medical Center, Miami, Florida 33125, USA. mmccarth@med.miami.edu
He
Jun
J
Auger
Denise
D
Geffin
Rebeca
R
Woodson
Cristina
C
Hutto
Cecelia
C
Wood
Charles
C
Scott
Gwendolyn
G
D001253:Astrocytes / Q000166:cytology / Q000821:virology; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D017628:Microglia / Q000166:cytology / Q000821:virology; D009422:Nervous System Diseases / Q000150:complications*; D011446:Prospective Studies; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism*; D013997:Time Factors; D019562:Viral Load
C515350:CCR3 protein, human; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D015728:Receptors, HIV