Document 3289
 DOCN  M94A3289
 TI    Selective susceptibility of human epidermal Langerhans cells to HIV-1
       infection in vitro.
 DT    9412
 AU    Soto-Ramirez LE; Renjifo B; Wang W; Marlink R; Lee TH; Essex M;
       Department of Cancer Biology, Harvard School of Public Health,; Boston,
       Massachusetts 02115.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):11 (abstract no. 018A). Unique
       Identifier : AIDSLINE ICA10/94369286
 AB    OBJECTIVE: A selective mechanism is probably involved in HIV-1
       transmission upon primary infection. As Langerhans cells (LC) can be the
       primary contact of the virus in heterosexual transmission, the
       susceptibility of these cells to three HIV-1 infectious molecular clones
       with defined tropism was investigated. METHODS: LC were isolated from
       normal human skin by a discontinuous density gradient; purity was judged
       by CD1a expression. Three infectious molecular clones were used: one
       with T-cell tropic and syncytium-inducing phenotype, HXB2RU3, and two
       non-syncytium-inducing, macrophage- tropic, chimeric viruses with
       envelope fragments of JRFLSBm and ADA.GG on a HXB2RU3 backbone. Assays:
       24 hrs. after isolation 0.5 x 10(6) LC were challenged (day 1) with
       virus stocks (10(5) cpm/ml) generated by transfection of Cos-7 cells, re
       challenged on day 3, and washed on day 5. Reverse transcriptase (RT)
       activity was assayed on days 7, 10 and 14. On day 14, cells were used
       for immunofluorescence (IF). LC plus medium was used as a negative
       control. All assays were done by duplicate. RESULTS: LC challenged with
       JRFLSBm/HXB2RU3 molecular clone showed no RT elevation and a negative
       IF. LC challenged with either HXB2RU3 or ADA. GG/HXB2RU3 showed high
       levels of RT as well as positive IF. The levels of RT on day 14 were
       higher for ADA.GG/HXB2RU3 (7.4 x 10(5) cpm/ml) than for HXBRU3 (1.8 x
       10(5)). No cytopathic effect was seen. CONCLUSIONS: LC HIV-1 infection
       in vitro revealed selectivity, with no apparent relation to T-cell
       tropic or macrophage-tropic phenotype. Replication otherwise, was more
       pronounced in the macrophage-tropic virus ADA.GG/HXB2RU3 than in
       HXB2RU3. If LC are the primary HIV-1 infected cells in heterosexual
       transmission, this selective susceptibility on infection and the
       differential replication found according to RT levels, could end in
       acquisition of a predominant phenotype, as has been seen after primary
       infection. As the V3 regions of ADA.GG and JRFLSBm are identical, other
       envelope sequences should be involved in the infection of LC.
 DE    Fluorescent Antibody Technique  Human  HIV Infections/*TRANSMISSION
       *HIV-1  In Vitro  Langerhans Cells/*MICROBIOLOGY  Reverse
       Transcriptase/ANALYSIS  Transfection  MEETING ABSTRACT

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