Retrograde and anterograde transport of HIV protein gp120 in the nervous system.
Neurodegeneration and gliosis are prominent pathological features of subjects with human immunodeficiency virus (HIV) dementia complex (HAD). In these patients, neurodegeneration occurs in uninfected neurons. In addition, these patients develop sensory neuropathy despite the antiretroviral therapy. The HIV protein gp120, which mimics some of the pathological alterations seen in HAD, is retrogradely transported in rodent neurons. However, it is still unclear whether gp120 can also be transported anterogradely and whether axonal transport can occur in the peripheral nervous system (PNS). To determine whether gp120 is transported retrogradely and/or anterogradely, we injected gp120IIIB together with the retrograde tracer fluoro-ruby (FR) or the anterograde tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyamine perchlorate (DiI) into the rat superior colliculi. We discovered that gp120 is retrogradely transported with FR along a direct pathway from the superior colliculus to the retina and anterogradely transported with DiI to several areas of the occipital cortex. To determine whether gp120 is also axonally transported in the peripheral nerves, gp120 and FR were injected into the sciatic nerve. No gp120 immunoreactivity was found in the sciatic nerve or dorsal root ganglia, suggesting that gp120 axonal transport does not occur in the PNS. Gp120 axonal transport may play a role in neuronal injury. Therefore, we examined apoptosis at various time points after gp120 injection. Activated caspase-3 was evident within neurons transporting gp120. These results indicate that axonal transport of gp120 might exacerbate the pathogenesis of HIV-1.
Ahmed
Farid
F
Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04 Box 571464, 3970 Reservoir Rd, NW, Washington, DC 20057, USA.
MacArthur
Linda
L
De Bernardi
Maria A
MA
Mocchetti
Italo
I
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001370:Axonal Transport / Q000187:drug effects; D015153:Blotting, Western; D002232:Carbocyanines; D053148:Caspase 3 / Q000378:metabolism; D003911:Dextrans; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology*; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D009778:Occipital Lobe / Q000187:drug effects / Q000378:metabolism; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D013477:Superior Colliculi / Q000187:drug effects / Q000378:metabolism
D002232:Carbocyanines; D003911:Dextrans; C067661:Fluoro-Ruby; D015699:HIV Envelope Protein gp120; D012235:Rhodamines; C072024:carbocyanine dye DiIC12(3); D053148:Caspase 3