title: Mode of transmission affects the sensitivity of human immunodeficiency virus type 1 to restriction by rhesus TRIM5alpha.
abstract: Rhesus TRIM5alpha (rhTRIM5alpha), but not human TRIM5alpha (huTRIM5alpha), potently inhibits human immunodeficiency virus (HIV) infection and is thus a potentially valuable therapeutic tool. Primary human CD4 T cells engineered to express rhTRIM5alpha were highly resistant to cell-free HIV type 1 (HIV-1) infection. However, when cocultured with unmodified T cells, rhTRIM5alpha-expressing cells became highly permissive to HIV-1 infection. Physical separation of rhTRIM5alpha-expressing cells and unmodified cells revealed that rhTRIM5alpha efficiently restricts cell-free but not cell-associated HIV transmission. Furthermore, we observed that HIV-infected human cells could infect rhesus CD4 T cells by cell-to-cell contact, but the infection was self-limiting. Subsequently, we noted that a spreading infection ensued when HIV-1-infected rhTRIM5alpha-expressing human cells were cultured with huTRIM5alpha- but not rhTRIM5alpha-expressing cells. Our results suggest that cell-associated HIV transmission in humans is blocked only when both donor and recipient cells express rhTRIM5alpha. These studies further define the role of rhTRIM5alpha in cell-free and cell-associated HIV transmission and delineate the utility of rhTRIM5alpha in anti-HIV therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104. rileyj@mail.med.upenn.edu.
authors.forename: Max W
authors.initials: MW
authors.lastname: Richardson
authors.forename: Richard G
authors.initials: RG
authors.lastname: Carroll
authors.forename: Matthew
authors.initials: M
authors.lastname: Stremlau
authors.forename: Nikolay
authors.initials: N
authors.lastname: Korokhov
authors.forename: Laurent M
authors.initials: LM
authors.lastname: Humeau
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
authors.forename: James L
authors.initials: JL
authors.lastname: Riley