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M9480496.TXT
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1994-08-20
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Document 0496
DOCN M9480496
TI Macrophage-tropic and T-cell line-adapted chimeric strains of human
immunodeficiency virus type 1 differ in their susceptibilities to
neutralization by soluble CD4 at different temperatures.
DT 9410
AU O'Brien WA; Mao SH; Cao Y; Moore JP; Department of Medicine, Veterans
Affairs Medical Center, West Los; Angeles, CA 90073.
SO J Virol. 1994 Aug;68(8):5264-9. Unique Identifier : AIDSLINE
MED/94309194
AB Molecular clones of three macrophage-tropic and three T-cell
line-adapted strains of human immunodeficiency virus type 1 (HIV-1) were
used to explore the mechanism of HIV-1 resistance to neutralization by
soluble CD4 (sCD4). The three macrophage-tropic viruses, each possessing
the V3 and flanking regions of JR-FL, were all resistant to sCD4
neutralization under the standard conditions of a short preincubation of
the virus and sCD4 at 37 degrees C prior to inoculation of peripheral
blood mononuclear cells. In contrast, the three T-cell line-adapted
viruses, NL4-3 and two chimeras possessing the V3 and flanking regions
of NL4-3 in the envelope background of JR-FL, were all sCD4 sensitive
under these conditions. Sensitivity to sCD4 neutralization at 37 degrees
C corresponded with rapid, sCD4-induced gp120 shedding from the viruses.
However, when the incubation temperature of the sCD4 and virus was
reduced to 4 degrees C, the three macrophage-tropic viruses shed gp120
and became more sensitive to sCD4 neutralization. In contrast, the rates
of sCD4-induced gp120 shedding and virus neutralization were reduced for
the three T-cell line-adapted viruses at 4 degrees C. Thus, HIV
resistance to sCD4 is a conditional phenomenon; macrophage-tropic and
T-cell line-adapted strains can be distinguished by the temperature
dependencies of their neutralization by sCD4. The average density of
gp120 molecules on the macrophage-tropic viruses exceeded by about
fourfold that on the T-cell line-adapted viruses, suggesting that HIV
growth in T-cell lines may select for a destabilized envelope
glycoprotein complex. Further studies of early events in HIV-1 infection
should focus on primary virus strains.
DE Adaptation, Physiological Antigens, CD4/*PHARMACOLOGY Human HIV
Envelope Protein gp120/METABOLISM HIV-1/*PHYSIOLOGY
Macrophages/*MICROBIOLOGY Neutralization Tests Solubility Support,
Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't,
P.H.S. T-Lymphocytes/*MICROBIOLOGY Temperature JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).