title: The replicative restriction of lymphocytotropic isolates of HIV-1 in macrophages is overcome by TGF-beta.
abstract: In vitro exposure of human blood monocyte-derived macrophages to T-cell tropic human immunodeficiency virus (HIV) isolates fails to establish a productive viral infection. Several studies have shown that such preferential HIV-1 replication in T cells or in mononuclear phagocytes (HIV tropism) may be determined by distinct viral characteristics. In the present study it was demonstrated that transforming growth factor-beta (TGF-beta), a factor known to be produced by platelets, macrophages, and other cells present at a wound site, can act as a mediator in overcoming the lymphocytotropic restriction of several well-characterized viral isolates of HIV-1 (i.e., LAV, Z84, pLAI, NY5). Macrophages infected with these isolates show cytopathic changes comparable to those seen upon infection with the monocytotropic isolate ADA. To achieve this effect with TGF-beta, the factor must be present after the infection period. The emerging virus retains its original cellular tropism. Based on these observations the authors propose a role for TGF-beta in the establishment and progression of HIV infection and disease.
authors.affiliation: CIBA-GEIGY Ltd., Pharma Research, Basel, Switzerland.
authors.forename: J K
authors.initials: JK
authors.lastname: Lazdins
authors.forename: T
authors.initials: T
authors.lastname: Klimkait
authors.forename: K
authors.initials: K
authors.lastname: Woods-Cook
authors.forename: M
authors.initials: M
authors.lastname: Walker
authors.forename: E
authors.initials: E
authors.lastname: Alteri
authors.forename: D
authors.initials: D
authors.lastname: Cox
authors.forename: N
authors.initials: N
authors.lastname: Cerletti
authors.forename: R
authors.initials: R
authors.lastname: Shipman
authors.forename: G
authors.initials: G
authors.lastname: Bilbe
authors.forename: G
authors.initials: G
authors.lastname: McMaster
mesh_terms: D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D008264:Macrophages / Q000382:microbiology*; D010586:Phagocytes / Q000382:microbiology; D010641:Phenotype; D013601:T-Lymphocytes / Q000382:microbiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014779:Virus Replication
chemical_list: D016212:Transforming Growth Factor beta