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M94A3289.TXT
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1994-10-25
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).