HIV infection of human fetal neural cells is mediated by gp120 binding to a cell membrane-associated molecule that is not CD4 nor galactocerebroside.
HIV infection of central nervous system (CNS) tissue is a common finding in both adult and pediatric AIDS. Because most children are believed to be infected perinatally, we have developed a model of HIV CNS infection that utilizes explant organotypic cultures of human fetal CNS tissue. Using this model we previously reported that both lymphocytotropic and monocytotropic HIV isolates infect microglia and astrocytes. However, the mechanism by which HIV infects these cells remains to be elucidated. We have observed that neural cell infection in these cultures may be the result of receptor-mediated endocytosis. In order to confirm this observation and to determine the ligand responsible for this process, organotypic cultures were exposed to untreated HIV, HIV pretreated with soluble CD4 (sCD4) or, as a control, heat-inactivated HIV. To address the question of a putative receptor for HIV infection, CNS cultures were either untreated or pretreated with gp120 or with the deglycosylated form of this protein. Other cultures were treated with antibodies to CD4 (anti-T4A) or to galactocerebroside (GC). Results demonstrate that pretreatment of either HIV with sCD4 or CNS cultures with gp120 significantly inhibits HIV infection. The inhibition of infection was demonstrated by a reduction in the number of cells positive for HIV proteins and by decreases in HIV proviral DNA and p24 production. Pretreatment of CNS cultures with deglycosylated gp120, anti-T4A or anti-GC antibodies did not inhibit HIV infection. These data suggest that HIV gp120 is needed for binding to a surface molecule on CNS cells that is not CD4 nor GC and that this molecule may function as a receptor and lead to infection of neural cells.
Hao
H N
HN
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Chiu
F C
FC
Losev
L
L
Weidenheim
K M
KM
Rashbaum
W K
WK
Lyman
W D
WD
D000328:Adult; D001253:Astrocytes / Q000378:metabolism / Q000821:virology; D015704:CD4 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D004705:Endocytosis / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005699:Galactosylceramides / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017628:Microglia / Q000378:metabolism / Q000821:virology; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology*; D016133:Polymerase Chain Reaction; D014779:Virus Replication
D015704:CD4 Antigens; D004279:DNA, Viral; D005699:Galactosylceramides; D015699:HIV Envelope Protein gp120