Mucosal tissue tropism and dissemination of HIV-1 subtype B acute envelope-expressing chimeric virus

Academic Article

Abstract

  • Human immunodeficiency virus type 1 (HIV-1) transmission results from infection with one or a small number of variants from the donor quasispecies. Transmitted/founder (T/F) viruses have recently been identified from acutely infected patients, but the way in which they interact with primary targets of HIV-1 infection is poorly understood. We have conducted a biological characterization of a panel of subtype B T/F acute and chronic envelope (Env)-expressing chimeric virus in primary human target cells and mucosal tissues. Both acute and chronic Envs preferentially replicated in peripheral blood mononuclear cells (PBMC) and a CD4 T-cell line compared to monocyte-derived macrophages, or dendritic cells (DC). In a model of trans infection from monocyte- derived dendritic cells to T cells, chimeric virus from acute Envs achieved significantly lower titers compared to chronic Envs. Challenge of primary human mucosal tissues revealed significantly higher levels of replication in chronic Env-expressing virus in rectal tissue compared to cervical and penile tissues and enhanced replication in tonsillar tissue relative to acute Envs. In agreement with data from the DC to T-cell trans infection assay, chronic Env-chimeric virus pools were transmitted more efficiently by migratory cells from cervical and penile tissues to CD4+ T cells than individual acute Env chimeras. These data indicate that virus with HIV-1 Envs of transmitted acute infections preferentially replicate in T cells ratherthan macrophages or dendritic cells and are less efficiently transmitted from antigen-presenting cells to CD4 T cells than chronic Envs. Such properties together with chemokine (C-C motif) receptor 5 (CCR5) use may confer an advantage for transmission. © 2013, American Society for Microbiology.
  • Digital Object Identifier (doi)

    Author List

  • King DFL; Siddiqui AA; Buffa V; Fischetti L; Gao Y; Stieh D; Mckay PF; Rogers P; Ochsenbauer C; Kappes JC
  • Start Page

  • 890
  • End Page

  • 899
  • Volume

  • 87
  • Issue

  • 2