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HIV-1 inhibition by human TRIM5-Cyp ...

Columbia University.

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HIV-1 inhibition by human TRIM5-Cyp fusion proteins.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	HIV-1 inhibition by human TRIM5-Cyp fusion proteins./
作者:	Neagu, Martha Raluca.
面頁冊數:	212 p.
附註:	Adviser: Jeremy Luban.
Contained By:	Dissertation Abstracts International70-01B.
標題:	Biology, Microbiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3343524
ISBN:	9780549984641

HIV-1 inhibition by human TRIM5-Cyp fusion proteins.
Neagu, Martha Raluca.

HIV-1 inhibition by human TRIM5-Cyp fusion proteins. - 212 p.

Adviser: Jeremy Luban.

Thesis (Ph.D.)--Columbia University, 2009.

Aotus monkeys synthesize an extraordinary TRIM5-cyclophilin A fusion protein (AoT5Cyp) that potently blocks HIV-1 infection. We attempted to generate an HIV-1 inhibitor modeled after AoT5Cyp by fusing human CypA to hT5 (hT5Cyp). Of 13 fusions, three were as potent as AoT5Cyp. Antiviral activity required capsid-binding by hCypA, linkage of hCypA to the capsid-specificity determinant in hT5alpha, and the ability to form cytoplasmic bodies. CXCR4- and CCR5-tropic HIV-1 clones and primary isolates were inhibited by hT5Cyp, as were HIV-2ROD, SIVAGMtan, FIVPET, and even a circulating HIV-1 isolate previously reported as AoT5Cyp-resistant. hT5Cyp blocked HIV-1 infection of primary CD4+ T cells and macrophages, and conferred a survival advantage without disruption of host cell function or selection for resistant virus. When compared with rhesus macaque T5alpha, or to hT5aalpha that had been modified to restrict HIV-1, hT5Cyp exhibited superior anti-HIV-1 activity. To test the effect of hT5Cyp on HIV-1 replication and pathogenesis in vivo, Rag2 -/-gammac-/- mice were engrafted with hCD4+ T cells that had been transduced by optimized lentiviral vectors bearing hT5Cyp. Upon challenge with either cell-free or cell-associated HIV-1, hT5Cyp decreased viremia and productive infection in lymphoid organs and preserved hCD4+ T cells. Thus, hT5Cyp is a robust inhibitor of HIV-1 replication in vivo.

ISBN: 9780549984641Subjects--Topical Terms:

1017734
Biology, Microbiology.

HIV-1 inhibition by human TRIM5-Cyp fusion proteins.
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