Genomic sites of human immunodeficiency virus type 2 (HIV-2) integration: similarities to HIV-1 in vitro and possible differences in vivo.
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.
MacNeil
Adam
A
Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., Boston, MA 02115, USA.
Sankalé
Jean-Louis
JL
Meloni
Seema Thakore
ST
Sarr
Abdoulaye Dieng
AD
Mboup
Souleymane
S
Kanki
Phyllis
P
D001482:Base Composition; D001665:Binding Sites; D002877:Chromosomes, Human / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015894:Genome, Human; D015497:HIV-1 / Q000235:genetics*; D015498:HIV-2 / Q000235:genetics*; D006570:Heterochromatin / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000821:virology; D008969:Molecular Sequence Data; D016662:Virus Integration; D014779:Virus Replication
D004279:DNA, Viral; D006570:Heterochromatin