ZNRD1 (zinc ribbon domain-containing 1) is a host cellular factor that influences HIV-1 replication and disease progression.

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Serval ID
serval:BIB_73B94B30F3B7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ZNRD1 (zinc ribbon domain-containing 1) is a host cellular factor that influences HIV-1 replication and disease progression.
Journal
Clinical Infectious Diseases
Author(s)
Ballana Ester, Senserrich Jordi, Pauls Eduardo, Faner Rosa, Maria Mercader Josep, Uyttebroeck Frederic, Palou Eduard, Pau Mena Maria, Grau Eulalia, Clotet Bonaventura, Ruiz Lidia, Telenti Amalio, Ciuffi Angela, Este Jose A.
ISSN
1537-6591[electronic], 1058-4838[linking]
Publication state
Published
Issued date
2010
Volume
50
Number
7
Pages
1022-1032
Language
english
Abstract
BACKGROUND: Human immunodeficiency virus (HIV) takes advantage of multiple host proteins to support its own replication. The gene ZNRD1 (zinc ribbon domain-containing 1) has been identified as encoding a potential host factor that influenced disease progression in HIV-positive individuals in a genomewide association study and also significantly affected HIV replication in a large-scale in vitro short interfering RNA (siRNA) screen. Genes and polymorphisms identified by large-scale analysis need to be followed up by means of functional assays and resequencing efforts to more precisely map causal genes. METHODS: Genotyping and ZNRD1 gene resequencing for 208 HIV-positive subjects (119 who experienced long-term nonprogression [LTNP] and 89 who experienced normal disease progression) was done by either TaqMan genotyping assays or direct sequencing. Genetic association analysis was performed with the SNPassoc package and Haploview software. siRNA and short hairpin RNA (shRNA) specifically targeting ZNRD1 were used to transiently or stably down-regulate ZNRD1 expression in both lymphoid and nonlymphoid cells. Cells were infected with X4 and R5 HIV strains, and efficiency of infection was assessed by reporter gene assay or p24 assay. RESULTS: Genetic association analysis found a strong statistically significant correlation with the LTNP phenotype (single-nucleotide polymorphism rs1048412; [Formula: see text]), independently of HLA-A10 influence. siRNA-based functional analysis showed that ZNRD1 down-regulation by siRNA or shRNA impaired HIV-1 replication at the transcription level in both lymphoid and nonlymphoid cells. CONCLUSION: Genetic association analysis unequivocally identified ZNRD1 as an independent marker of LTNP to AIDS. Moreover, in vitro experiments pointed to viral transcription as the inhibited step. Thus, our data strongly suggest that ZNRD1 is a host cellular factor that influences HIV-1 replication and disease progression in HIV-positive individuals.
Keywords
Whole-Genome Association, Major Determinants, HLA-C, Infection, Resistance, Genes, AIDS, RNA, Identification, Integration
Pubmed
Web of science
Open Access
Yes
Create date
25/03/2010 17:10
Last modification date
25/09/2019 6:09
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