Proliferation-dependent replication in primary macrophages of macrophage-tropic HIV type 1 variants.
We previously demonstrated that completion of reverse transcription in macrophages inoculated with the HIV-1 Ba-L variant was established only in the subpopulation of cells with proliferative capacity. In our present study we further extended this observation with three additional HIV-1 isolates, being the macrophage-tropic ADA strain and two primary macrophage-tropic HIV-1 variants isolated from cerebrospinal fluid and from bronchoalveolar lavage from AIDS patients. On inoculation, irrespective of the virus variant used, elongated reverse transcription products could be demonstrated only in macrophages that had proliferated during inoculation as evidenced by the incorporation of bromodeoxyuridine (BrdU), a thymidine analog. The presence of newly synthesized early products of reverse transcription also in the BrdU-negative fraction indicated that viral entry is not disturbed in nondividing cells. Our data indicate that the process of reverse transcription is dependent on cellular conditions that coincide with cell proliferation, and therefore that HIV-1 replication is restricted to cells with proliferative potential.
Kootstra
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NA
Department of Clinical Viral Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Academic Medical Center, University of Amsterdam.
Schuitemaker
H
H
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology; D001483:Base Sequence; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D014644:Genetic Variation; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D014779:Virus Replication
D017931:DNA Primers; D001973:Bromodeoxyuridine