DEFECTIVE ACCESSORY GENES IN A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED LONG-TERM SURVIVOR LACKING RECOVERABLE VIRUS

被引:108
作者
MICHAEL, NL
CHANG, G
DARCY, LA
EHRENBERG, PK
MARIANI, R
BUSCH, MP
BIRX, DL
SCHWARTZ, DH
机构
[1] HENRY M JACKSON FDN, ROCKVILLE, MD USA
[2] JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT MOLEC MICROBIOL & IMMUNOL, BALTIMORE, MD USA
[3] COLD SPRING HARBOR LAB, COLD SPRING HARBOR, NY 11724 USA
[4] IRWIN MEM BLOOD CTR, SAN FRANCISCO, CA USA
关键词
D O I
10.1128/JVI.69.7.4228-4236.1995
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We have been studying a patient who acquired human immunodeficiency virus (HIV) infection via a blood transfusion 13 years ago. She has remained asymptomatic since that time. The blood donor and two other recipients have all died of AIDS. Although this patient has shown persistently strong seroreactivity to HIV type 1 (HIV-1) antigens by Western blot (immunoblot), she has been continually HIV culture negative in results from multiple laboratories over the last 6 years and has a very low viral burden. Her CD4(+) T-cell count has fluctuated around a mean of 399 cells per mu l, with little change in lymphocyte subset percentages. Strong cellular immune responses to HIV-1 epitopes by this patient have been demonstrated. We now report the results of an intensive molecular genetic analysis of the HIV-1 proviral quasispecies from this patient sampled over 5 years. Long terminal repeat region sequences supported the argument for normal basal and Tat-mediated promoter activities. Sequential sequencing of the nef gene revealed a low frequency (8.3%) of defective genes and a striking lack of sequence evolution, Functional analysis of predominant nef genes by both a cell surface CD4 downregulation and a viral infectivity complementation assay showed wild-type function. In contrast, sequential analysis of an amplicon containing the vif, vpr, vpu, tat1, and rev1 genes revealed the presence of inactivating mutations in 64% of the clones. These data suggest that this patient, initially infected with a virulent swarm of HIV-1, is presently infected with a more-attenuated viral quasispecies as a result of effective host immunity.
引用
收藏
页码:4228 / 4236
页数:9
相关论文
共 69 条
  • [1] NEF INDUCES CD4 ENDOCYTOSIS - REQUIREMENT FOR A CRITICAL DILEUCINE MOTIF IN THE MEMBRANE-PROXIMAL CD4 CYTOPLASMIC DOMAIN
    AIKEN, C
    KONNER, J
    LANDAU, NR
    LENBURG, ME
    TRONO, D
    [J]. CELL, 1994, 76 (05) : 853 - 864
  • [2] NEF FROM PRIMARY ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SUPPRESSES SURFACE CD4 EXPRESSION IN HUMAN AND MOUSE T-CELLS
    ANDERSON, S
    SHUGARS, DC
    SWANSTROM, R
    GARCIA, JV
    [J]. JOURNAL OF VIROLOGY, 1993, 67 (08) : 4923 - 4931
  • [3] 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
  • [4] REGULATION OF HUMAN-IMMUNODEFICIENCY-VIRUS NEF PROTEIN BY PHOSPHORYLATION
    BANDRES, JC
    LURIA, S
    RATNER, L
    [J]. VIROLOGY, 1994, 201 (01) : 157 - 161
  • [5] DOWN-REGULATION OF CELL-SURFACE CD4 EXPRESSION BY SIMIAN IMMUNODEFICIENCY VIRUS NEF PREVENTS VIRAL SUPER INFECTION
    BENSON, RE
    SANFRIDSON, A
    OTTINGER, JS
    DOYLE, C
    CULLEN, BR
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (06) : 1561 - 1566
  • [6] CD4 CELL-SURFACE DOWN-REGULATION IN HIV-1 NEF TRANSGENIC MICE IS A CONSEQUENCE OF INTRACELLULAR SEQUESTRATION
    BRADY, HJM
    PENNINGTON, DJ
    MILES, CG
    DZIERZAK, EA
    [J]. EMBO JOURNAL, 1993, 12 (13) : 4923 - 4932
  • [7] BUSCH MP, 1994, COMMUNICATION
  • [8] HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPU PROTEIN INDUCES DEGRADATION OF CD4 INVITRO - THE CYTOPLASMIC DOMAIN OF CD4 CONTRIBUTES TO VPU SENSITIVITY
    CHEN, MY
    MALDARELLI, F
    KARCZEWSKI, MK
    WILLEY, RL
    STREBEL, K
    [J]. JOURNAL OF VIROLOGY, 1993, 67 (07) : 3877 - 3884
  • [9] OPTIMAL INFECTIVITY IN-VITRO OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REQUIRES AN INTACT NEF GENE
    CHOWERS, MY
    SPINA, CA
    KWOH, TJ
    FITCH, NJS
    RICHMAN, DD
    GUATELLI, JC
    [J]. JOURNAL OF VIROLOGY, 1994, 68 (05) : 2906 - 2914
  • [10] Clark S J, 1993, Semin Immunol, V5, P149, DOI 10.1006/smim.1993.1018