Genomic Sites of Human Immunodeficiency Virus Type 2 (Hiv-2) Integration: Similarities to Hiv-1 in Vitro and Possible Differences in Vivo.
From: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., Boston, MA 02115, USA.
Journal of virology
- Publish Date: Aug 2006
- ISSN: 0022-538X
- Volume: 80
- Issue: 15
- Pages: 7316-21
- Medium: Print
- Language: English
- Citation (JAMA): MacNeil Adam, Sankalé Jean-Louis, Meloni Seema Thakore, et al. Genomic Sites of Human Immunodeficiency Virus Type 2 (Hiv-2) Integration: Similarities to Hiv-1 in Vitro and Possible Differences in Vivo.. J. Virol. Aug 2006;80:7316-21
Abstract
Retroviruses have distinct preferences in integration site selection in the host cell genome during in vitro infection, with human immunodeficiency virus type 1 (HIV-1) integration strongly favoring transcriptional units. Additionally, studies with HIV-1 have shown that the genomic site of proviral integration may impact viral replication, with integration in heterochromatin associated with a block in viral transcription. HIV-2 is less pathogenic than HIV-1 and is believed to have a lower replication rate in vivo. Although differences in integration site selection between HIV-2 and HIV-1 could potentially explain the attenuated pathogenicity of HIV-2, no studies have characterized integration site selection by HIV-2. In this study, we mapped 202 HIV-2 integration sites during in vitro infection of peripheral blood mononuclear cells with a primary HIV-2 isolate. In addition, we assayed for in vivo proviral integration within heterochromatin in 21 HIV-1-infected subjects and 23 HIV-2-infected subjects, using an alphoid repeat PCR assay. During in vitro infection, HIV-2 displayed integration site preferences similar to those previously reported for HIV-1. Notably, 82% of HIV-2 integrations mapped to Refseq genes, and integration strongly favored regions of the genome with high gene density and high GC content. Though rare, the proportion of HIV-2 subjects with evidence of proviral integration within heterochromatin in vivo was higher than that of HIV-1-infected subjects. It is therefore possible that integration site selection may play a role in the differences in HIV-1 and HIV-2 in vivo pathogenesis.
Mesh Headings (Keywords): Base Composition, Binding Sites, Chromosomes, Human, DNA, Viral, Female, Genome, Human, HIV-1, HIV-2, Heterochromatin, Humans, Leukocytes, Mononuclear, Molecular Sequence Data, Virus Integration, Virus Replication
Check for Full Text / PubMed Unique Identifier (PMID): 16840312
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