title: Mucosal tissue tropism and dissemination of HIV-1 subtype B acute envelope-expressing chimeric virus.
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 rather than 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.
authors.affiliation: Centre for Infection, Clinical Sciences, St. George's University of London, London, United Kingdom.
authors.forename: Deborah F L
authors.initials: DF
authors.lastname: King
authors.forename: Asna A
authors.initials: AA
authors.lastname: Siddiqui
authors.forename: Viviana
authors.initials: V
authors.lastname: Buffa
authors.forename: Lucia
authors.initials: L
authors.lastname: Fischetti
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.forename: Daniel
authors.initials: D
authors.lastname: Stieh
authors.forename: Paul F
authors.initials: PF
authors.lastname: McKay
authors.forename: Paul
authors.initials: P
authors.lastname: Rogers
authors.forename: Christina
authors.initials: C
authors.lastname: Ochsenbauer
authors.forename: John C
authors.initials: JC
authors.lastname: Kappes
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Arts
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000821:virology; D003713:Dendritic Cells / Q000821:virology; D005260:Female; D005838:Genotype; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology; D008297:Male; D009092:Mucous Membrane / Q000821:virology*; D010413:Penis / Q000821:virology; D012007:Rectum / Q000821:virology; D056189:Viral Tropism; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D054299:env Gene Products, Human Immunodeficiency Virus