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).