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Differential type 1 interferon‐regulated gene expression in the brain during AIDS: interactions with viral diversity and neurovirulence
Author(s) -
Polyak Maria J.,
Vivithanaporn Pornpun,
Maingat Ferdinand G.,
Walsh John G.,
Branton William,
Cohen Eric A.,
Meeker Rick,
Power Christopher
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-227868
Subject(s) - gene , virology , interferon , biology , differential (mechanical device) , diversity (politics) , gene expression , genetics , physics , sociology , anthropology , thermodynamics
The lentiviruses, human and feline immunodeficiency viruses (HIV‐1 and FIV, respectively), infect the brain and cause neurovirulence, evident as neuronal injury, inflammation, and neurobehavioral abnormalities with diminished survival. Herein, different lentivirus infections in conjunction with neural cell viability were investigated, concentrating on type 1 interferon‐regulated pathways. Transcriptomic network analyses showed a preponderance of genes involved in type 1 interferon signaling, which was verified by increased expression of the type 1 interferon‐associated genes, Mx1 and CD317 , in brains from HIV‐infected persons ( P <0.05). Leukocytes infected with different strains of FIV or HIV‐1 showed differential Mx1 and CD317 expression ( P <0.05). In vivo studies of animals infected with the FIV strains, FIV ch or FIV ncsu , revealed that FIV ch ‐infected animals displayed deficits in memory and motor speed compared with the FIV ncsu ‐ and mock‐infected groups ( P <0.05). TNF‐α, IL‐1β , and CD40 expression was increased in the brains of FIV ch ‐infected animals; conversely, Mx1 and CD317 transcript levels were increased in the brains of FIV ncsu ‐infected animals, principally in microglia ( P <0.05). Gliosis and neuronal loss were evident among FIV ch ‐infected animals compared with mock‐ and FIV ncsu ‐infected animals ( P <0.05). Lentiviral infections induce type 1 interferon‐regulated gene expression in microglia in a viral diversity‐dependent manner, representing a mechanism by which immune responses might be exploited to limit neurovirulence.—Polyak, M. J., Vivithanaporn, P., Maingat, F. G., Walsh, J. G., Branton, W., Cohen, E. A., Meeker, R., Power, C. Differential type 1 interferon‐regulated gene expression in the brain during AIDS: interactions with viral diversity and neurovirulence. FASEB J. 27, 2829‐2844 (2013). www.fasebj.org