Skip to main content
SpringerLink
Log in
Book cover

Humanized Mice for HIV Research pp 305–312Cite as

Brain HIV-1 Infection Modeling in Humanized Mice

  • Chapter
  • First Online:

Abstract

The HIV-1-associated neurologic disorders were described earlier in HIV-1 pandemia and are now recognized as a complex of pathologic changes related to the HIV-1 infection of brain perivascular and resident cells, such as microglia. At the same time, the significant contribution to the neurocognitive deficit in humans could be related to the secondary events, such as chronic emotional stress, chronic immune activation due to mucosal barriers deficiency, opportunistic viral and bacterial infections, malnutrition, and other factors that could not be excluded or controlled like on experimental laboratory animals. Animals carrying human hemato-lymphoid tissue and chronically infected with HIV-1 could provide valuable information about the pathogenesis of neurocognitive dysfunction and serve as a model for therapeutic development.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

CSF-1:

Monocyte-colony stimulating factor

DNA-PKcs:

Catalytic subunit of the DNA-dependent protein kinase

HAND:

HIV-1-associated neurologic disorders

HSC:

Hematopoietic stem cells

IL-2Rγc :

Interleukin-2 receptor common gamma chain

NSG/NOG:

NOD/Shi LtJ-scid/IL2Rγnull mice

scid :

Severe combined immune deficiency

SIRP- α:

Signal regulatory protein-α

References

  1. Epstein LG, Sharer LR, Cho ES, Myenhofer M, Navia B, Price RW. HTLV-III/LAV-like retrovirus particles in the brains of patients with AIDS encephalopathy. AIDS Res. 1984;1(6):447–54.

    Article  PubMed  Google Scholar 

  2. Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2010;17(1):3–16.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, et al. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science. 1986;233(4768):1089–93.

    Article  CAS  PubMed  Google Scholar 

  4. Epstein LG, Sharer LR, Gajdusek DC. Hypothesis: AIDS encephalopathy is due to primary and persistent infection of the brain with a human retrovirus of the lentivirus subfamily. Med Hypotheses. 1986;21(1):87–96.

    Article  CAS  PubMed  Google Scholar 

  5. Blacklaws BA. Small ruminant lentiviruses: immunopathogenesis of visna-maedi and caprine arthritis and encephalitis virus. Comp Immunol Microbiol Infect Dis. 2012;35(3):259–69.

    Article  PubMed  Google Scholar 

  6. Tyor WR, Power C, Gendelman HE, Markham RB. A model of human immunodeficiency virus encephalitis in scid mice. Proc Natl Acad Sci U S A. 1993;90(18):8658–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Persidsky Y, Limoges J, McComb R, Bock P, Baldwin T, Tyor W, et al. Human immunodeficiency virus encephalitis in SCID mice. Am J Pathol 1996;149(3):1027–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  8. Bissel SJ, Wiley CA. Human immunodeficiency virus infection of the brain: pitfalls in evaluating infected/affected cell populations. Brain Pathol. 2004;14(1):97–108.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Koppensteiner H, Brack-Werner R, Schindler M. Macrophages and their relevance in human immunodeficiency virus type I infection. Retrovirology. 2012;9:82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Gorantla S, Makarov E, Finke-Dwyer J, Castanedo A, Holguin A, Gebhart CL, et al. Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis. Am J Pathol. 2010;177(6):2938–49.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Gorantla S, Makarov E, Finke-Dwyer J, Gebhart CL, Domm W, Dewhurst S, et al. CD8 + cell depletion accelerates HIV-1 immunopathology in humanized mice. J Immunol. 2010;184(12):7082–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Dou H, Morehead J, Bradley J, Gorantla S, Ellison B, Kingsley J, et al. Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brain. Glia. 2006;54(2):81–93.

    Article  PubMed  Google Scholar 

  13. Gorantla S, Liu J, Sneller H, Dou H, Holguin A, Smith L, et al. Copolymer-1 induces adaptive immune anti-inflammatory glial and neuroprotective responses in a murine model of HIV-1 encephalitis. J Immunol. 2007;179(7):4345–56.

    Article  CAS  PubMed  Google Scholar 

  14. Forsman A, Weiss RA. Why is HIV a pathogen? Trends Microbiol. 2008;16(12):555–60.

    Article  CAS  PubMed  Google Scholar 

  15. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010;330(6005):841–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Horiuchi M, Wakayama K, Itoh A, Kawai K, Pleasure D, Ozato K, et al. Interferon regulatory factor 8/interferon consensus sequence binding protein is a critical transcription factor for the physiological phenotype of microglia. J Neuroinflammation. 2012;9:227.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C, Cella M, et al. IL-34 is a tissuerestricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol. 2012;13(8):753–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Kierdorf K, Erny D, Goldmann T, Sander V, Schulz C, Perdiguero EG, et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat Neurosci. 2013;16(3):273–80.

    Article  CAS  PubMed  Google Scholar 

  19. Verney C, Monier A, Fallet-Bianco C, Gressens P. Early microglial colonization of the human forebrain and possible involvement in periventricular white-matter injury of preterm infants. J Anat. 2010;217(4):436–48.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Asheuer M, Pflumio F, Benhamida S, Dubart-Kupperschmitt A, Fouquet F, Imai Y, et al. Human CD34 + cells differentiate into microglia and express recombinant therapeutic protein. Proc Natl Acad Sci U S A. 2004;101(10):3557–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Dash PK, Gorantla S, Gendelman HE, Knibbe J, Casale GP, Makarov E, et al. Loss of neuronal integrity during progressive HIV-1 infection of humanized mice. J Neurosci. 2011;31(9):3148–57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Towgood KJ, Pitkanen M, Kulasegaram R, Fradera A, Kumar A, Soni S, et al. Mapping the brain in younger and older asymptomatic HIV-1 men: frontal volume changes in the absence of other cortical or diffusion tensor abnormalities. Cortex. 2012;48(2):230–41.

    Article  PubMed  Google Scholar 

  23. Muller-Oehring EM, Schulte T, Rosenbloom MJ, Pfefferbaum A, Sullivan EV. Callosal degradation in HIV-1 infection predicts hierarchical perception: a DTI study. Neuropsychologia. 2010;48(4):1133–43.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Liu Y, Sajja BR, Gendelman HE, Boska MD. Mouse brain fixation to preserve In vivo manganese enhancement for ex vivo manganese-enhanced MRI. J Magn Reson Imaging. 24 Jan 2013. doi:10.1002/jmri.24005.

    Google Scholar 

Download references

Acknowledgments

This contribution was supported by the Chair of the Department of Pharmacology and Experimental Neuroscience Dr. Howard E. Gendelman and grants P01 NS043985 DHHS/NIH/NINDS, P01 DA028555 DHHS/NIH/NIDA, R01AG043540. The authors would like to thank Edward Makarov, Jaclyn Knibbe-Hollinger, Tanuja Gutti, Prashanta Dash, Aditya Bade, and Sidra Akhter for ongoing contributions in humanized mice for NeuroAIDS projects.

Author information

Authors and Affiliations

  1. Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, 68198-5880, Omaha, NE, USA

    Larisa Y. Poluektova MD, PhD, Adrian A. Epstein & Santhi Gorantla

Authors
  1. Larisa Y. Poluektova MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adrian A. Epstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Santhi Gorantla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Larisa Y. Poluektova MD, PhD .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA

    Larisa Y. Poluektova

  2. Center for AIDS Research, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    J. Victor Garcia

  3. Research Center for AIDS Laboratory of Viral Pathogenesis, Kyoto University Institute for Virus Research, Sakyo-ku, Japan

    Yoshio Koyanagi

  4. Division of Hematology, University Hospital Zürich, Zürich, Switzerland

    Markus G. Manz

  5. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

    Andrew M. Tager

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Poluektova, L., Epstein, A., Gorantla, S. (2014). Brain HIV-1 Infection Modeling in Humanized Mice. In: Poluektova, L., Garcia, J., Koyanagi, Y., Manz, M., Tager, A. (eds) Humanized Mice for HIV Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1655-9_25

Download citation

Publish with us

Policies and ethics

Search

Navigation