INFECTIOUS VIRUS WITH REDUCED CYTOPATHOGENICITY RESULTING FROM PERSISTENT INFECTION OF NORMAL LUNG FIBROBLASTS BY HIV TYPE-1 STRAINS

被引:10
作者
DOLEI, A
SERRA, C
ARCA, MV
TILOCCA, F
RIVA, E
ANTONELLI, G
DIANZANI, F
TONIOLO, A
机构
[1] UNIV ROMA LA SAPIENZA,INST VIROL,I-00185 ROME,ITALY
[2] UNIV PISA,DEPT BIOMED,I-56127 PISA,ITALY
[3] UNIV PAVIA,DEPT MED & PUBL HLTH,I-2100 VARESE,ITALY
关键词
D O I
10.1089/aid.1994.10.1089
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We asked whether HIV-1 had the capacity to establish a persistent infection of cultured human diploid fibroblasts. Human strains of normal diploid embryo lung fibroblasts were infected with HIV-1 of the HTLV-IIIB and HIV-1(P1) strains. Infection was followed over time, to analyze HIV expression. Virus production (intra- and extracellular virus) was evaluated as follows: ability to form syncytia in the C8166 T cell line, production of p24 and other viral antigens (ELISA and indirect immunofluorescence), search for a gag sequence in cell DNA by the polymerase chain reaction followed by hybridization to an HIV-1-specific probe (SK19). Cell-free culture supernatant was used as a virus source to infect de novo fibroblasts and C8166 T cells. Infection of cultured fibroblasts with either the HTLV-IIIB or HIV-1(P1) strain led regularly to the establishment of persistently infected cultures. Fibroblast cells were capable of continuous virus production for at least 10 months. The released virus was capable of reinfecting cultured fibroblasts and of producing cytopathic effects in the C8166 T cell line. However, when compared to wild-type strains, the infectious virus derived from fibroblasts showed a prolonged replication cycle and a decreased ability to form syncytia in the T cell line. Therefore, HIV-1 can establish a persistent and productive infection in normal lung fibroblasts. The data are consistent with the hypothesis that in vivo, at least in the lung, fibroblasts may represent a virus reservoir and that infection of these cells may lead to the production of attenuated variants of HIV.
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页码:1089 / 1095
页数:7
相关论文
共 39 条
[1]   FERRITIN DOWN-REGULATION IN HIV-INFECTED CELLS [J].
AMEGLIO, F ;
TILOCCA, F ;
ARCA, MV ;
ALEMANNO, L ;
DOLEI, A .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 1993, 9 (08) :795-798
[2]   PROSTAGLANDIN-A INHIBITS REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS DURING ACUTE INFECTION [J].
ANKEL, H ;
TURRIZIANI, O ;
ANTONELLI, G .
JOURNAL OF GENERAL VIROLOGY, 1991, 72 :2797-2800
[3]   CELLULAR PROTEINS BOUND TO IMMUNODEFICIENCY VIRUSES - IMPLICATIONS FOR PATHOGENESIS AND VACCINES [J].
ARTHUR, LO ;
BESS, JW ;
SOWDER, RC ;
BENVENISTE, RE ;
MANN, DL ;
CHERMANN, JC ;
HENDERSON, LE .
SCIENCE, 1992, 258 (5090) :1935-1938
[4]   INFECTION OF CULTURED HUMAN ADRENAL-CELLS BY DIFFERENT STRAINS OF HIV [J].
BARBOZA, A ;
CASTRO, BA ;
WHALEN, M ;
MOORE, CCD ;
PARKIN, JS ;
MILLER, WL ;
GONZALEZSCARANO, F ;
LEVY, JA .
AIDS, 1992, 6 (12) :1437-1443
[5]   MECHANISMS OF HIV-1 LATENCY [J].
BEDNARIK, DP ;
FOLKS, TM .
AIDS, 1992, 6 (01) :3-16
[6]   CD4-INDEPENDENT, PRODUCTIVE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF HEPATOMA-CELL LINES INVITRO [J].
CAO, YZ ;
FRIEDMANKIEN, AE ;
HUANG, YX ;
LI, XL ;
MIRABILE, M ;
MOUDGIL, T ;
ZUCKERFRANKLIN, D ;
HO, DD .
JOURNAL OF VIROLOGY, 1990, 64 (06) :2553-2559
[7]   HUMAN-IMMUNODEFICIENCY-VIRUS CAN PRODUCTIVELY INFECT CULTURED HUMAN GLIAL-CELLS [J].
CHENGMAYER, C ;
RUTKA, JT ;
ROSENBLUM, ML ;
MCHUGH, T ;
STITES, DP ;
LEVY, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (10) :3526-3530
[8]   ALTERED HOST RANGE OF HIV-1 AFTER PASSAGE THROUGH VARIOUS HUMAN CELL-TYPES [J].
CHENGMAYER, C ;
SETO, D ;
LEVY, JA .
VIROLOGY, 1991, 181 (01) :288-294
[9]   SOLUBLE CD4 BLOCKS THE INFECTIVITY OF DIVERSE STRAINS OF HIV AND SIV FOR T-CELLS AND MONOCYTES BUT NOT FOR BRAIN AND MUSCLE-CELLS [J].
CLAPHAM, PR ;
WEBER, JN ;
WHITBY, D ;
MCINTOSH, K ;
DALGLEISH, AG ;
MADDON, PJ ;
DEEN, KC ;
SWEET, RW ;
WEISS, RA .
NATURE, 1989, 337 (6205) :368-370
[10]   PLASMA VIREMIA IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTION [J].
COOMBS, RW ;
COLLIER, AC ;
ALLAIN, JP ;
NIKORA, B ;
LEUTHER, M ;
GJERSET, GF ;
COREY, L .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 321 (24) :1626-1631