VPR DELETION MUTANT OF SIMIAN IMMUNODEFICIENCY VIRUS INDUCES AIDS IN RHESUS-MONKEYS

被引:80
作者
HOCH, J
LANG, SM
WEEGER, M
STAHLHENNIG, C
COULIBALY, C
DITTMER, U
HUNSMANN, G
FUCHS, D
MULLER, J
SOPPER, S
FLECKENSTEIN, B
UBERLA, KT
机构
[1] UNIV ERLANGEN NURNBERG, INST KLIN & MOLEK VIROL, D-91054 ERLANGEN, GERMANY
[2] DEUTSCH PRIMATENZENTRUM GMBH, W-3400 GOTTINGEN, GERMANY
[3] UNIV WURZBURG, INST PATHOL, W-8700 WURZBURG, GERMANY
[4] UNIV WURZBURG, INST VIROL & IMMUNBIOL, W-8700 WURZBURG, GERMANY
[5] UNIV INNSBRUCK, INST MED CHEM & BIOCHEM, A-6020 INNSBRUCK, AUSTRIA
[6] LUDWIG BOLTZMANN INST AIDS FORSCH, INNSBRUCK, AUSTRIA
关键词
D O I
10.1128/JVI.69.8.4807-4813.1995
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In previous experiments, animals infected with SIVmac239 containing a point mutation in the vpr and nef genes developed AIDS-like symptoms after early reversion of the vpr and nef genes. Here we show that two animals in which the nef gene but not the vpr gene had reverted in the first few months did not develop disease during a 3-year observation period even after reversion to a functional vpr gene 70 weeks postinfection. To study the influence of a stable vpr mutation on virus load and pathogenesis, a 43-bp deletion was introduced into the vpr gene of SIVmac2390n, a nef-open mutant of SIVmac239, Four rhesus monkeys were inoculated with the vpr deletion mutant (SIV Delta vpr), and two control animals were infected with SIVmac239on. Both control animals had persistent antigenemia, high cell-associated virus loads, and elevated neopterin levels. They had to be euthanized 20 and 30 weeks postinfection because of AIDS-related symptoms. However, all four rhesus monkeys inoculated with SIV Delta vpr showed only transiently detectable antigenemia. The cell-associated virus loads were high in three of the four animals. Two animals with AIDS-like symptoms had to be euthanized 71 and 73 weeks postinfection. The two remaining monkeys infected,vith SIV Delta vpr were still alive 105 weeks postinfection. In contrast to the SIVmac239on-infected animals, SIV Delta vpr-infected animals had strong humoral immune responses and intermittent cellular immune responses to SIV antigens. Our data show that a functional vpr gene is not necessary for pathogenesis. However, vpr-deficient SIVmac239 variants might be slightly attenuated, allowing some animals to resist progression to disease for an extended period of time.
引用
收藏
页码:4807 / 4813
页数:7
相关论文
共 30 条
  • [1] DISTINCT EFFECTS IN PRIMARY MACROPHAGES AND LYMPHOCYTES OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACCESSORY GENES VPR, VPU, AND NEF - MUTATIONAL ANALYSIS OF A PRIMARY HIV-1 ISOLATE
    BALLIET, JW
    KOLSON, DL
    EIGER, G
    KIM, FM
    MCGANN, KA
    SRINIVASAN, A
    COLLMAN, R
    [J]. VIROLOGY, 1994, 200 (02) : 623 - 631
  • [2] STABLE GROWTH TRANSFORMATION OF HUMAN LYMPHOCYTES-T BY HERPESVIRUS SAIMIRI
    BIESINGER, B
    MULLERFLECKENSTEIN, I
    SIMMER, B
    LANG, G
    WITTMANN, S
    PLATZER, E
    DESROSIERS, RC
    FLECKENSTEIN, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) : 3116 - 3119
  • [3] COHEN EA, 1990, J ACQ IMMUN DEF SYND, V3, P11
  • [4] HUMAN-IMMUNODEFICIENCY-VIRUS VPR PRODUCT IS A VIRION-ASSOCIATED REGULATORY PROTEIN
    COHEN, EA
    DEHNI, G
    SODROSKI, JG
    HASELTINE, WA
    [J]. JOURNAL OF VIROLOGY, 1990, 64 (06) : 3097 - 3099
  • [5] DITTMER U, 1994, J MED PRIMATOL, V23, P21
  • [6] NEOPTERIN AS A MARKER FOR ACTIVATED CELL-MEDIATED-IMMUNITY - APPLICATION IN HIV INFECTION
    FUCHS, D
    HAUSEN, A
    REIBNEGGER, G
    WERNER, ER
    DIERICH, MP
    WACHTER, H
    [J]. IMMUNOLOGY TODAY, 1988, 9 (05): : 150 - 155
  • [7] FUCHS D, 1988, CLIN CHEM, V34, P2415
  • [8] ROLE OF HUMORAL-FACTORS IN THE PROGRESSION OF HIV DISEASE
    FUST, G
    DIERICH, MP
    HIDVEGI, T
    [J]. IMMUNOLOGY TODAY, 1995, 16 (04): : 167 - 169
  • [9] PROGRESSION TO AIDS IN THE ABSENCE OF A GENE FOR VPR OR VPX
    GIBBS, JS
    LACKNER, AA
    LANG, SM
    SIMON, MA
    SEHGAL, PK
    DANIEL, MD
    DESROSIERS, RC
    [J]. JOURNAL OF VIROLOGY, 1995, 69 (04) : 2378 - 2383
  • [10] CONSTRUCTION AND IN-VITRO PROPERTIES OF SIV(MAC) MUTANTS WITH DELETIONS IN NONESSENTIAL GENES (VOL 10, PG 333, 1994)
    GIBBS, JS
    REGIER, DA
    DESROSIERS, RC
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 1994, 10 (05) : 607 - 616