title: Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4(+) T cells.
abstract: The host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4(+) T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the acute phase of infection. A total of 1,484 unique HIV-1 integration sites were analysed. Their distribution in the human genome and genetic features, and the effects of HIV-1 integrase polymorphisms on the nucleotide selection specificity at these sites were indistinguishable between the two cell types, and among HIV-1 isolates. However, the repertoires of HIV-1-hosting gene clusters overlapped to a higher extent in MDMs than in CD4(+) T cells. The frequencies of HIV-1 integration events in genes encoding HIV-1-interacting proteins were also different between the two cell types. Lastly, HIV-1-hosting genes linked to clonal expansion of latently HIV-1-infected CD4(+) T cells were over-represented in gene hotspots identified in CD4(+) T cells but not in those identified in MDMs. Taken together, the repertoire of genes targeted by HIV-1 in MDMs is distinct from and more restricted than that of CD4(+) T cells.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Yik Lim
authors.initials: YL
authors.lastname: Kok
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vongrad
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Mohaned
authors.initials: M
authors.lastname: Shilaih
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Giallonardo
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Herbert
authors.initials: H
authors.lastname: Kuster
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Kouyos
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Metzner
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D039002:Prophages / Q000235:genetics*; D016662:Virus Integration