Evidence of blood-brain barrier alteration and activation in HIV-1 gp120 transgenic mice.
OBJECTIVE
To verify whether HIV envelope protein gp120 changes the blood-brain barrier in vivo, as a fundamental mechanism of early central nervous system damage by HIV-1.


METHODS
Analysis of the functional integrity and immune activation of the blood-brain barrier in brains of HIV-1 gp120 transgenic mice secreting circulating gp120 at levels similar to those detected in AIDS patients.


METHODS
Number of vessels/mm2 section area with perivascular albumin and percentage of vessels expressing adhesion molecules (ICAM-1 and VCAM-1) were determined by immunohistochemistry in frozen brains from autopsied transgenic and non-transgenic mice. The percentage of vessels showing substance P immunoreactivity was also calculated, as this neuropeptide is known to mediate the increase in permeability of the rat brain endothelium in vitro caused by HIV-1 gp120.


RESULTS
The number of vessels with albumin extravasation was significantly higher in transgenic than non-transgenic mice brains (P = 0.0003). A greater percentage of ICAM-1- and VCAM-1-positive brain vessels in transgenic than non-transgenic mice was shown (P = 0.0017 and P = 0.0008 respectively). Significant immunoreactivity for substance P was detected in brain vessels in transgenic mice and a significant correlation was found between the percentage of substance P-positive and ICAM-1-positive brain vessels (P < 0.0001) in transgenic mice.


CONCLUSIONS
These findings demonstrate that HIV-1 gp120 is capable of changing and activating in vivo the vascular component of the blood-brain barrier.
Toneatto
S
S
Institute of Neurological Sciences, University of Siena, Italy.
Finco
O
O
van der Putten
H
H
Abrignani
S
S
Annunziata
P
P
D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013373:Substance P / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger; D012367:RNA, Viral; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P