HIV-1 propagates in human neuroblastoma cells.
A major question in the pathogenesis of AIDS encephalopathy and dementia is whether HIV-1 directly infects cells of the central nervous system (CNS). The propagation of HIV was attempted in six cell lines: three related and three unrelated to the nervous system. HIV was able to propagate in two human neuroblastoma cell lines and a lymphocytic cell line control but did not result in infections of African green monkey kidney cells, human cervix carcinoma cells, and one human brain astrocytoma cell line. Neuroblastoma cell lines infected with HIV showed peaks of reverse transcriptase activity at 10-14 days postinfection. After prolonged growth in cell cultures, one of the neuroblastoma cell lines showed multiphasic virus production, additional high peaks of reverse transcriptase activity, 20-fold greater than the first, lasting from 36 to 74 days and 110 to 140 days postinfection. The presence of HIV was confirmed by p24 antigen capture. The neuroblastoma cell lines had weak but detectable levels of CD4 immunoreactivity by immunoperoxidase and flow immunocytometric analysis. Although no T4-specific RNA sequences were detected by hybridization of Northern blots of total and poly A-selected RNA extracted from the two neuroblastoma cell lines by using a T4 specific complimentary DNA probe, monoclonal antibodies to the CD4 receptor blocked HIV infection in both neuroblastoma cell lines. Thus, the infection of neuroblastoma cells by HIV occurs in part by a CD4-dependent mechanism. Passaging the neuroblastoma cell lines weekly and bimonthly resulted in similar cell cycle-DNA content patterns for the more permissive cell line and with significant numbers of cells in the S phase. HIV-infected neuroblastoma cell lines provide an in vitro model for the evaluation of virus-host cell interactions and may be useful in addressing the issue of the persistence of HIV in the human CNS.
Shapshak
P
P
Pearlman Research Center, Miami Beach, Florida.
Sun
N C
NC
Resnick
L
L
Thornthwaite
J T
JT
Schiller
P
P
Yoshioka
M
M
Svenningsson
A
A
Tourtellotte
W W
WW
Imagawa
D T
DT
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D002453:Cell Cycle; D015683:Gene Products, gag / Q000032:analysis; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009447:Neuroblastoma / Q000382:microbiology* / Q000473:pathology; D009474:Neurons / Q000382:microbiology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014758:Viral Core Proteins / Q000032:analysis; D014779:Virus Replication
D015704:CD4 Antigens; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D014758:Viral Core Proteins; D012194:RNA-Directed DNA Polymerase