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

被引:55
作者
OBRIEN, WA [1 ]
MAO, SH [1 ]
CAO, YZ [1 ]
MOORE, JP [1 ]
机构
[1] NYU, SCH MED, AARON DIAMOND AIDS RES CTR, NEW YORK, NY USA
关键词
D O I
10.1128/JVI.68.8.5264-5269.1994
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页码:5264 / 5269
页数:6
相关论文
共 34 条
  • [1] PRODUCTION OF ACQUIRED IMMUNODEFICIENCY SYNDROME-ASSOCIATED RETROVIRUS IN HUMAN AND NONHUMAN CELLS TRANSFECTED WITH AN INFECTIOUS MOLECULAR CLONE
    ADACHI, A
    GENDELMAN, HE
    KOENIG, S
    FOLKS, T
    WILLEY, R
    RABSON, A
    MARTIN, MA
    [J]. JOURNAL OF VIROLOGY, 1986, 59 (02) : 284 - 291
  • [2] ARNOLD E, 1991, ADV VIRUS RES, V39, P1
  • [3] RESISTANCE OF PRIMARY ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TO SOLUBLE CD4 IS INDEPENDENT OF CD4-RGP120 BINDING-AFFINITY
    ASHKENAZI, A
    SMITH, DH
    MARSTERS, SA
    RIDDLE, L
    GREGORY, TJ
    HO, DD
    CAPON, DJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (16) : 7056 - 7060
  • [4] ENVELOPE PROTEINS FROM CLINICAL ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 THAT ARE REFRACTORY TO NEUTRALIZATION BY SOLUBLE CD4 POSSESS HIGH-AFFINITY FOR THE CD4 RECEPTOR
    BRIGHTY, DW
    ROSENBERG, M
    CHEN, ISY
    IVEYHOYLE, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (17) : 7802 - 7805
  • [5] CANN AJ, 1988, ONCOGENE, V3, P123
  • [6] JITTERS JEOPARDIZE AIDS VACCINE TRIALS
    COHEN, J
    [J]. SCIENCE, 1993, 262 (5136) : 980 - 981
  • [7] HIGH-CONCENTRATIONS OF RECOMBINANT SOLUBLE CD4 ARE REQUIRED TO NEUTRALIZE PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES
    DAAR, ES
    LI, XL
    MOUDGIL, T
    HO, DD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (17) : 6574 - 6578
  • [8] FISHER R, 1991, AIDS RES REV, V1, P289
  • [9] HIV INFECTION IS BLOCKED INVITRO BY RECOMBINANT SOLUBLE CD4
    FISHER, RA
    BERTONIS, JM
    MEIER, W
    JOHNSON, VA
    COSTOPOULOS, DS
    LIU, T
    TIZARD, R
    WALKER, BD
    HIRSCH, MS
    SCHOOLEY, RT
    FLAVELL, RA
    [J]. NATURE, 1988, 331 (6151) : 76 - 78
  • [10] CHANGES IN BOTH GP120 AND GP41 CAN ACCOUNT FOR INCREASED GROWTH-POTENTIAL AND EXPANDED HOST RANGE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1
    FUJITA, K
    SILVER, J
    PEDEN, K
    [J]. JOURNAL OF VIROLOGY, 1992, 66 (07) : 4445 - 4451