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Elucidation of retroviral capsid res...

Ulm, Jacob Wesley.

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Elucidation of retroviral capsid residues involved in modulation of murine and human cell post-entry restriction.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Elucidation of retroviral capsid residues involved in modulation of murine and human cell post-entry restriction./
作者:	Ulm, Jacob Wesley.
面頁冊數:	167 p.
附註:	Adviser: Richard C. Mulligan.
Contained By:	Dissertation Abstracts International67-05B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3217910
ISBN:	9780542694264

Elucidation of retroviral capsid residues involved in modulation of murine and human cell post-entry restriction.
Ulm, Jacob Wesley.

Elucidation of retroviral capsid residues involved in modulation of murine and human cell post-entry restriction. - 167 p.

Adviser: Richard C. Mulligan.

Thesis (Ph.D.)--Harvard University, 2006.

The species and tissue tropisms of retroviruses are generally regarded as functions of the viral envelope, but recent work has thoroughly characterized the integral role of the viral capsid (CA) gene product in affecting the tropism of murine leukemia viruses (MLVs) and lentiviruses like HIV, restricting infection at a post-entry stage. So-called N and B alleles of Fv1, a murine cellular inhibitor, selectively restrict "B-tropic" and "N-tropic" MLVs, respectively, on the basis of the viral capsid residue at CA110; a human agent (Ref1) selectively blocks pseudotyped N-MLV; and variants of Lv1 in human and monkey cells restrict lentiviruses. Details about capsid-host inhibitor interactions remain poorly characterized, however; little is known about specific regions in the capsid that affect sensitivity to CA110-based restriction, or that enable some MLVs to attain dual tropism and thus escape Fv1 and Ref1 restriction. Basic questions about the evolution of host restriction factors and retroviral evasion of restriction also remain unanswered.

ISBN: 9780542694264Subjects--Topical Terms:

1017730
Biology, Genetics.

Elucidation of retroviral capsid residues involved in modulation of murine and human cell post-entry restriction.
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245 1 0 $a Elucidation of retroviral capsid residues involved in modulation of murine and human cell post-entry restriction.
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520 $a The species and tissue tropisms of retroviruses are generally regarded as functions of the viral envelope, but recent work has thoroughly characterized the integral role of the viral capsid (CA) gene product in affecting the tropism of murine leukemia viruses (MLVs) and lentiviruses like HIV, restricting infection at a post-entry stage. So-called N and B alleles of Fv1, a murine cellular inhibitor, selectively restrict "B-tropic" and "N-tropic" MLVs, respectively, on the basis of the viral capsid residue at CA110; a human agent (Ref1) selectively blocks pseudotyped N-MLV; and variants of Lv1 in human and monkey cells restrict lentiviruses. Details about capsid-host inhibitor interactions remain poorly characterized, however; little is known about specific regions in the capsid that affect sensitivity to CA110-based restriction, or that enable some MLVs to attain dual tropism and thus escape Fv1 and Ref1 restriction. Basic questions about the evolution of host restriction factors and retroviral evasion of restriction also remain unanswered.
520 $a Here we present studies that have characterized and elucidated the substantial role played by specific residues in the CA protein of Moloney MLV in sensitizing the retrovirus to both Fv1 and Ref1 restriction, focusing in particular on CA82. We have detailed its potentiation of post-entry restriction and amassed evidence to illuminate its possible role in host-virus interactions and co-evolution. We have compared the murine and human restrictions of Moloney MLV variants and carried out studies to better define the nature of the host inhibitor-viral capsid interactions in both Fv1 and Ref1 restrictions. We have characterized an apparently conserved restriction pattern in the avian spleen necrosis virus (SNV), and have demonstrated that the inhibition against both retroviruses is mediated by TRIM5alphahu, the recently-discovered agent of Ref1 restriction. Finally, we have elucidated a novel restriction pattern evident in Chinese hamster ovary-K (CHO-K) cells, which may indicate the presence of a new set of restriction factors for further study. Our work may find application in studies of viral evolution, crystallographic analysis, and gene therapy and antiviral drug development efforts.
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