The visna virus long terminal repeat directs expression of a reporter gene in activated macrophages, lymphocytes, and the central nervous systems of transgenic mice.
Visna virus is a lentivirus which causes a slow progressive disease involving the immune system and the central nervous system. To determine the role of the viral long terminal repeat (LTR) in targeting the virus to specific host cells and tissues, transgenic mice were constructed which contained the visna virus LTR directing expression of the bacterial gene encoding chloramphenicol acetyltransferase (CAT). Analysis of the transgenic mouse tissues for CAT activity revealed that the viral LTR was responsible, in part, for the tropism of visna virus for macrophages and the central nervous system. Expression of the LTR required the macrophage to be in an activated state both in vivo and in vitro. Thioglycolate activation of peritoneal macrophages in vivo and 12-O-tetradecanoylphorbol 13-acetate treatment in vitro induced expression of the visna virus LTR. Lymphocytes from the spleens of the transgenic mice expressed CAT activity, suggesting that visna virus was able to replicate in lymphocytes, as did human immunodeficiency virus and simian immunodeficiency virus. These studies demonstrated that the lentivirus LTR was responsible, in part, for cell and tissue tropism in vivo.
Small
J A
JA
Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Bieberich
C
C
Ghotbi
Z
Z
Hess
J
J
Scangos
G A
GA
Clements
J E
JE
D000818:Animals; D002490:Central Nervous System / Q000502:physiology*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology*; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D014018:Tissue Distribution; D014790:Visna-maedi virus / Q000235:genetics*
D015500:Chloramphenicol O-Acetyltransferase