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Compartmentalization and evolution of feline immunodeficiency virus between the central nervous system and periphery following intracerebroventricular or systemic inoculation

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Abstract

The emergence of distinct neuropathogenic strains resulting from the adaptation and the unique evolution of human immunodeficiency virus (HIV) in the brain may contribute to the development of HIV-induced neurological diseases. In this study, the authors tracked early changes in virus evolution and compartmentalization between peripheral tissues and the central nervous system (CNS) after intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) inoculation of animals with cell-free feline immunodeficiency virus (FIV). Using the FIV-NCSU1 envelope V3–V4 heteroduplex tracking assay (HTA), the authors observed a rapid compartmentalization of envelope variants between the CNS and periphery. Animals receiving the i.c.v. inoculation showed two peaks of viral RNA in the cerebrospinal fluid (CSF) with very different HTA patterns. Compared to the initial viral peak in CSF, the second peak showed an increased compartmentalization from plasma, reduced viral diversity, and more divergence from the proviral DNA in peripheral blood mononuclear cells (PBMCs) and the choroid plexus. In contrast, changes in plasma over the same time period were small. Different animals harbored different FIV DNA genotypes with varied regional compartmentalization within the brain. These results demonstrated that the virus within the CNS experienced a relatively independent but variable evolution from the periphery. Initial penetration of virus into the CSF facilitated the development of brain-specific reservoirs and viral diversification within the CNS.

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Author notes

  1. Thomas W. Vahlenkamp

    Present address: Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel, Riems, Germany

Authors and Affiliations

  1. Immunology Program, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA

    Pinghuang Liu, Lola C. Hudson, Mary B. Tompkins & Thomas W. Vahlenkamp

  2. Department of Neurology and Neurobiology Curriculum, University of North Carolina, 6109 Neuroscience Research Building, 103 Mason Farm Road, CB# 7025, 27599, Chapel Hill, NC, USA

    Rick B. Meeker

Authors
  1. Pinghuang Liu
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  2. Lola C. Hudson
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  3. Mary B. Tompkins
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  4. Thomas W. Vahlenkamp
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  5. Rick B. Meeker
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Corresponding author

Correspondence to Rick B. Meeker.

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The study was supported by National Institutes of Health grant MH63646.

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Liu, P., Hudson, L.C., Tompkins, M.B. et al. Compartmentalization and evolution of feline immunodeficiency virus between the central nervous system and periphery following intracerebroventricular or systemic inoculation. Journal of NeuroVirology 12, 307–321 (2006). https://doi.org/10.1080/13550280600889575

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  • DOI: https://doi.org/10.1080/13550280600889575

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