Journal of NeuroVirology

, Volume 15, Issue 2, pp 139–152 | Cite as

Dual lentivirus infection potentiates neuroinflammation and neurodegeneration: viral copassage enhances neurovirulence

  • Amir Afkhami-Goli
  • Shu-Hong Liu
  • Yu Zhu
  • Joseph M. Antony
  • Hosseinali Arab
  • Christopher Power
Article

Abstract

Infection by multiple lentiviral strains is recognized as a major driving force in the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic, but the neuropathogenic consequences of multivirus infections remain uncertain. Herein, we investigated the neurovirulence and underlying mechanisms of dual lentivirus infections with distinct viral strains. Experimental feline immunodeficiency virus (FIV) infections were performed using cultured cells and an in vivo model of AIDS neuropathogenesis. Dual infections were comprised of two FIV strains (FIV-Ch and FIV-PPR) as copassaged or superinfected viruses, with subsequent outcome analyses of host immune responses, viral load, neuropathological features, and neurobehavioral performance. Dual infections of feline macrophages resulted in greater IL-1β (interleukin-1b), TNF-α (tumor necrosis factor α), and IDO (indoleamine 2,3-dioxygenase) expression and associated neurotoxic properties. FIV coinfection and sequential superinfection in vivo also induced greater IL-1β, TNF-α, and IDO expression in the basal ganglia (BG) and cortex (CTX), compared to the monovirus- and mock-infected groups, although viral loads were similar in single virus and dual virusinfected animals. Immunoblot analyses disclosed lower synaptophysin immunoreactivity in the CTX resulting from FIV super- and coinfections. Cholinergic and GABAergic neuronal injury was evident in the CTX of animals with dual FIV infections. With increased glial activation and neuronal loss in dual FIV infected brains, immunohistochemical analysis also revealed elevated detection of cleaved caspase-3 in dysmorphic neurons, which was associated with worsened neurobehavioral abnormalities among animals infected with the copassaged viruses. Dual lentivirus infections caused an escalation in neuroinflammation and ensuing neurodegeneration, underscoring the contribution of infection by multiple viruses to neuropathogenesis.

Keywords

FIV nervous system dual infection neuroinflammation neuron glia apoptosis 

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Copyright information

© Journal of NeuroVirology, Inc. 2009

Authors and Affiliations

  • Amir Afkhami-Goli
    • 1
    • 2
  • Shu-Hong Liu
    • 3
  • Yu Zhu
    • 1
  • Joseph M. Antony
    • 1
  • Hosseinali Arab
    • 2
  • Christopher Power
    • 1
    • 3
  1. 1.Departments of Medicine and Medical Microbiology and ImmunologyUniversity of AlbertaEdmontonCanada
  2. 2.Department of Pharmacology, Faculty of Veterinary MedicineUniversity of TehranTehranIran
  3. 3.Department of Clinical NeurosciencesUniversity of CalgaryCalgaryCanada

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