Novel pathway of human immunodeficiency virus type 1 uptake and release in astrocytes

被引:33
|
作者
Clarke, JN
Lake, JA
Burrell, CJ
Wesselingh, SL
Gorry, PR
Li, P
机构
[1] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3001, Australia
[2] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia
[3] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia
[4] Australian Ctr HIV & Hepatitis Virol Res, Infect Dis Labs, Inst Med & Vet Sci, Adelaide, SA, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
HIV-1; astrocyte; reservoir; persistence; latency; replication;
D O I
10.1016/j.virol.2005.12.004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Astrocytes persistently infected with HIV-1 can transmit virus to CD4+ cells, Suggesting that astrocytes may be a source of viral persistence and dissemination in the brain. In the present study, we investigated the fate of HIV-1 upon infection of astrocytes. HIV-1 was observed in vesicle-like structures. Unspliced genomic RNA and extrachromosomal HIV-1 DNA were detected in astrocytes, with levels declining over time. The extrachromosomal viral DNA was not tie novo reverse transcribed in astrocytes but Most likely the products of intravirion reverse transcription present in the virus inoculum. Integrated HIV-1 DNA was not detected in assays sensitive to detect 2 integrated copies of provirus. However, the majority of astrocyte Cultures released infectious virus that Could be transmitted to CD4+ cells. Our findings suggest a novel pathway of HIV-1 uptake and release in astrocytes that does not necessarily require virus replication, which may contribute to persistence and spread of HIV-1 in the brain. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:141 / 155
页数:15
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