Use of a combined ex vivo/in vivo population approach for screening of human genes involved in the human immunodeficiency virus type 1 life cycle for variants influencing disease progression.

Abstract:

:Humans differ substantially with respect to susceptibility to human immunodeficiency virus type 1 (HIV-1). We evaluated variants of nine host genes participating in the viral life cycle for their role in modulating HIV-1 infection. Alleles were assessed ex vivo for their impact on viral replication in purified CD4 T cells from healthy blood donors (n = 128). Thereafter, candidate alleles were assessed in vivo in a cohort of HIV-1-infected individuals (n = 851) not receiving potent antiretroviral therapy. As a benchmark test, we tested 12 previously reported host genetic variants influencing HIV-1 infection as well as single nucleotide polymorphisms in the nine candidate genes. This led to the proposition of three alleles of PML, TSG101, and PPIA as potentially associated with differences in progression of HIV-1 disease. In a model considering the combined effects of new and previously reported gene variants, we estimated that their effect might be responsible for lengthening or shortening by up to 2.8 years the period from 500 CD4 T cells/mul to <200 CD4 T cells/mul.

journal_name

J Virol

journal_title

Journal of virology

authors

Bleiber G,May M,Martinez R,Meylan P,Ott J,Beckmann JS,Telenti A,Swiss HIV Cohort Study.

doi

10.1128/JVI.79.20.12674-12680.2005

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

12674-80

issue

20

eissn

0022-538X

issn

1098-5514

pii

79/20/12674

journal_volume

79

pub_type

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