当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progression.

Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progression.

Abstract：

:Originally recognized for their role in lipoprotein metabolism and cardiovascular disease, apolipoprotein (apo) E isoforms (apoE2, apoE3, and apoE4) have also been implicated to play a key role in several biological processes not directly related to their lipid transport function. For example, apoE4 contributes significantly to neurodegeneration in Alzheimer's disease. However, the role of apoE in infectious diseases is less well defined. Here, by examining a large cohort of HIV(+) European and African American subjects, we found that the APOE epsilon4/epsilon4 genotype is associated with an accelerated disease course and especially progression to death compared with the APOE epsilon3/epsilon3 genotype. However, an association between the epsilon4/epsilon4 genotype and HIV-associated dementia (HAD), a neurological condition with clinicopathological features similar to Alzheimer's disease, was not detected. Consistent with the genotype-phenotype relationships observed, compared with recombinant apoE3, apoE4 enhanced HIV fusion/cell entry of both R5 and X4 HIV strains in vitro. These findings establish apoE as a determinant of HIV-AIDS pathogenesis and raise the possibility that current efforts to convert apoE4 to an "apoE3-like" molecule to treat Alzheimer's disease might also have clinical applicability in HIV disease.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Burt TD,Agan BK,Marconi VC,He W,Kulkarni H,Mold JE,Cavrois M,Huang Y,Mahley RW,Dolan MJ,McCune JM,Ahuja SK

doi

10.1073/pnas.0803526105

subject

Has Abstract

pub_date

2008-06-24 00:00:00

pages

8718-23

issue

25

eissn

0027-8424

issn

1091-6490

pii

0803526105

journal_volume

105

pub_type

杂志文章

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