Impact of viral accessory proteins of SIVsmmPBj on early steps of infection of quiescent cells

Abstract

Although lentiviruses like HIV-1 are able to infect non-dividing cells, particular resting cells such as non-stimulated primary peripheral blood mononuclear cells (PBMC) are resistant to infection. In contrast to other lentiviruses, SIVsmmPBj can replicate in non-stimulated PBMC. Moreover, SIVsmmPBj-derived, but not HIV-1-derived, replication-incompetent vectors enable gene transfer into G(0)-arrested human cell lines and primary human monocytes. Here, we demonstrate that transduction of G(0)-arrested cell lines by SIVsmmPBj-derived vectors is independent of the viral accessory proteins Vif, Vpx, Vpr, or Nef. In contrast, for the transduction of primary human monocytes, the Vpx protein proved to be essential. However, trans-complementation of HIV-1 vectors with SIVsmmPBj Vpx did not provide the property of gene transfer into monocytes. Taken together, these data indicate that Vpx is essential for the infection of primary monocytes by SIVsmmPBj. Additionally, further genome functions besides the accessory proteins are required for the particular capacity of SIVsmmPBj in transduction or infection events.

Characterization of Simian Immunodeficiency Virus SIV SM /Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells

“…The data presented here underscore the preponderant role of Vpx during the infection of myeloid cells as opposed to lymphoid cells (in primary cells and in at least one cell line, THP-1), thus completing the emerging picture drawn from the previous work of several laboratories on the importance of this protein both ex vivo and in vivo (12,13,17,19,26,28,32,38,40,45).…”

Interaction of Vpx and Apolipoprotein B mRNA-editing Catalytic Polypeptide 3 Family Member A (APOBEC3A) Correlates with Efficient Lentivirus Infection of Monocytes

“…Primate lentiviruses of the human immunodeficiency virus type 2 (HIV-2) 5 and the simian immunodeficiency (SIVsm/ SIVmac) lineage uniquely encode for the viral protein Vpx. This 13-kDa accessory protein is packaged into budding virions by interaction with the p6 domain of Gag (1) and might have a role in early infection steps in target cells.…”

“…This 13-kDa accessory protein is packaged into budding virions by interaction with the p6 domain of Gag (1) and might have a role in early infection steps in target cells. Vpx has been shown to be crucial for infection of human monocytes and monocyte-derived cells as such as macrophages and dendritic cells in vitro, but is dispensable for infection of cell lines and primary lymphocytes (2)(3)(4)(5). In vivo, infection of monkeys by a mutant SIV lacking the vpx gene is characterized by a loss of pathogenicity (6).…”

Tailored HIV-1 Vectors for Genetic Modification of Primary Human Dendritic Cells and Monocytes

“…Contrary to more permissive cells, MDDCs, like other human myeloid cells (monocytes and macrophages), display a strong resistance to HIV-1, a phenomenon that is particularly acute during the early phases of infection, i.e., those phases of interest for gene therapy purposes (11)(12)(13). This relative resistance can be bypassed in certain instances through the use of high doses of viral inputs (14)(15)(16), but this exposes target cells to modifications that can affect their maturation, their survival, or their functionality and that are largely due to the presence of large amounts of viral components (8)(9)(10).…”

“…Several attempts have been carried out over the years to transfer the positive property of Vpx on lentiviral infection to HIV-1 LVs (16,22,24). Recently, this goal has been achieved by modifying the p6 domain of HIV-1 Gag through which Vpx is normally packaged into cognate viral particles (24).…”