The replicative restriction of lymphocytotropic isolates of HIV-1 in macrophages is overcome by TGF-beta.
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.
Lazdins
J K
JK
CIBA-GEIGY Ltd., Pharma Research, Basel, Switzerland.
Klimkait
T
T
Woods-Cook
K
K
Walker
M
M
Alteri
E
E
Cox
D
D
Cerletti
N
N
Shipman
R
R
Bilbe
G
G
McMaster
G
G
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
D016212:Transforming Growth Factor beta