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Journal of Virology, August 2006, p. 7316-7321, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.00604-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Genomic Sites of Human Immunodeficiency Virus Type 2 (HIV-2) Integration: Similarities to HIV-1 In Vitro and Possible Differences In Vivo

Adam MacNeil,1 Jean-Louis Sankalé,1 Seema Thakore Meloni,1 Abdoulaye Dieng Sarr,1 Souleymane Mboup,2 and Phyllis Kanki1*

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts,1 Laboratoire de Bacteriologie et Virologie, Universite Cheikh Anta Diop, Dakar, Senegal2

Received 24 March 2006/ Accepted 19 May 2006

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.

* Corresponding author. Mailing address: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., Boston, MA 02115. Phone: (617) 432-1267. Fax: (617) 432-3575. E-mail: pkanki{at}hsph.harvard.edu.

Journal of Virology, August 2006, p. 7316-7321, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.00604-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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