A Trim5-cyclophilin A fusion protein found in owl monkey kidney cells can restrict HIV-1.
نویسندگان
چکیده
Lv1 restriction of HIV-1 in the cells of Old World monkeys is associated with the expression of the Trim5 gene. Uniquely, in owl monkey kidney cells, HIV-1 restriction is dependent on the ability of incoming viral capsid protein to bind cyclophilin A (CypA). Cloning of the owl monkey Trim5 gene now reveals the presence of an inserted CypA pseudogene within intron 7 of the Trim5 gene. This insertion results in the formation of a chimeric Trim5-CypA transcript. Transfer of a cDNA corresponding to this transcript into human cells confers cyclosporin A-sensitive resistance to HIV-1 infection. The restriction factor appears to be a chimeric protein created by retrotransposon-mediated exon shuffling.
منابع مشابه
A novel fusion gene, TRIM5-Cyclophilin A in the pig-tailed macaque determines its susceptibility to HIV-1 infection.
OBJECTIVE In Old World monkeys, the tripartite motif 5alpha (TRIM5alpha) protein confers resistance to HIV-1 infection following virus entry into host cells. However, the pig-tailed macaque (Macaca nemestrina) is an exception and is susceptible to HIV-1 infection. This study dissects the molecular mechanism of the pig-tailed macaque's susceptibility to HIV-1 infection. METHODS Genomic sequenc...
متن کاملCyclophilin A is required for TRIM5 -mediated resistance to HIV-1 in Old World monkey cells
The peptidyl-prolyl isomerase cyclophilin A (CypA) embraces an exposed, proline-rich loop on HIV-1 capsid (CA) and renders reverse transcription complexes resistant to an antiviral activity in human cells. A CypA fusion with TRIM5 that is unique to New World owl monkeys also targets HIV-1 CA, but this interaction potently inhibits infection. A similar block to HIV-1 infection in Old World monke...
متن کاملNaturally occurring capsid substitutions render HIV-1 cyclophilin A independent in human cells and TRIM-cyclophilin-resistant in Owl monkey cells.
In this study, we asked if a naturally occurring HIV-1 variant exists that circumvents CypA dependence in human cells. To address this issue, we sought viruses for CypA independence using Debio-025, a cyclosporine A (CsA) analog that disrupts CypA-capsid interaction. Surprisingly, viral variants from the Main group replicate even in the presence of the drug. Sequencing analyses revealed that th...
متن کاملTrim-cyclophilin A fusion proteins can restrict human immunodeficiency virus type 1 infection at two distinct phases in the viral life cycle.
The Trim5alpha protein from several primates restricts retroviruses in a capsid (CA)-dependent manner. In owl monkeys, the B30.2 domain of Trim5 has been replaced by cyclophilin A (CypA) following a retrotransposition. Restriction of human immunodeficiency virus type 1 (HIV-1) by the resulting Trim5-CypA fusion protein depends on CA binding to CypA, suggesting both that the B30.2 domain might b...
متن کاملChance favors a prepared genome.
D uring evolution, all vertebrates have been exposed to multiple waves of crossspecies infection by retroviruses. A number of defensive strategies have developed, among them the spontaneous expression, throughout the body, of restriction factors, antiviral proteins that will bind to the capsid (CA) protein of incoming virions and interfere with virus replication (1). One example of such a prote...
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ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 101 36 شماره
صفحات -
تاریخ انتشار 2004