Proteomic modeling for HIV-1 infected microglia-astrocyte crosstalk.
BACKGROUND
HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system's microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease.


RESULTS
MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species.


CONCLUSIONS
These observations provide unique insights into glial crosstalk during disease by supporting astrocyte-mediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery and therapeutics that may influence the course of HIV-1-mediated neurodegeneration.
Wang
Tong
T
Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology and Experimental Neuroscience, Omaha, Nebraska, United States of America.
Gong
Nan
N
Liu
Jianuo
J
Kadiu
Irena
I
Kraft-Terry
Stephanie D
SD
Mosley
R Lee
RL
Volsky
David J
DJ
Ciborowski
Pawel
P
Gendelman
Howard E
HE
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000821:virology; D003599:Cytoskeleton; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology* / Q000821:virology; D011247:Pregnancy; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species