In vivo activation of human immunodeficiency virus type 1 long terminal repeat by UV type A (UV-A) light plus psoralen and UV-B light in the skin of transgenic mice.
UV irradiation has been shown to activate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in cell culture; however, only limited studies have been described in vivo. UV light has been categorized as UV-A (400 to 315 nm), -B (315 to 280 nm), or -C (less than 280 nm); the longer wavelengths are less harmful but more penetrative. Highly penetrative UV-A radiation constitutes the vast majority of UV sunlight reaching the earth's surface but is normally harmless. UV-B irradiation is more harmful but less prevalent than UV-A. In this report, the HIV-1 LTR-luciferase gene in the skin of transgenic mice was markedly activated when exposed to UV-B irradiation. The LTR in the skin of transgenic mice pretreated topically with a photosensitizing agent (psoralen) was also activated to similar levels when exposed to UV-A light. A 2-h exposure to sunlight activated the LTR in skin treated with psoralen, whereas the LTR in skin not treated with psoralen was activated after 7 h of sunlight exposure. The HIV-1 LTR-beta-galactosidase reporter gene was preferentially activated by UV-B irradiation in a small population of epidermal cells. The transgenic mouse models carrying HIV-1 LTR-luciferase and LTR-beta-galactosidase reporter genes have been used to demonstrate the in vivo UV-induced activation of the LTR and might be used to evaluate other environmental factors or pharmacologic substances that might potentially activate the HIV-1 LTR in vivo.
Morrey
J D
JD
AIDS Research Program, Utah State University, Logan 84322-5600.
Bourn
S M
SM
Bunch
T D
TD
Jackson
M K
MK
Sidwell
R W
RW
Barrows
L R
LR
Daynes
R A
RA
Rosen
C A
CA
D000818:Animals; D004279:DNA, Viral / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004817:Epidermis / Q000382:microbiology; D011564:Furocoumarins / Q000737:chemistry; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000528:radiation effects*; D016325:HIV Long Terminal Repeat / Q000187:drug effects / Q000528:radiation effects*; D015497:HIV-1 / Q000187:drug effects / Q000528:radiation effects*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000235:genetics
D004279:DNA, Viral; D011564:Furocoumarins; D008156:Luciferases; D001616:beta-Galactosidase