Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain

Yoshio Koyanagi, Yuetsu Tanaka, Jun Ichi Kira, Mamoru Ito, Kyoji Hioki, Naoko Misawa, Yuji Kawano, Kenji Yamasaki, Reiko Tanaka, Youichi Suzuki, Yoshito Ueyama, Eiji Terada, Toshiyuki Tanaka, Masayuki Miyasaka, Takuro Kobayashi, Yoshio Kumazawa, Naoki Yamamoto

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Abstract

We established four new mouse strains with defective T and B cells as well as defects in innate immunological reactions using an NK cell depletion antibody and showed that all mutant mouse strains efficiently received human peripheral blood leukocyte (PBL) engraftment (hu-PBL-scid mice). Higher levels of human immunodeficiency virus type 1 (HIV-1) replication were observed in these new hu-PBL-scid mice than in conventional hu-PBL-C.B-17- scid mice. In one particular strain, hu-PBL-NOD-scid mice, high levels of HIV-1 viremia (more than 106 50% infectious doses per ml) were detected after infection with HIV-1. The plasma viral load was about 100 to 1,000 times higher than that observed in other hu-PBL-scid mice infected with HIV- 1. Although high-level viremia did not correlate with the total amount of HIV-1 RNA in cells from infected mice, high levels of free virions were detected only in hu-PBL-NOD-scid mice. HIV-1 viremia induced systemic HIV-1 infection involving the liver, lungs, and brain. PCR in situ hybridization confirmed that HIV-1-infected cells invaded the brain tissue of the hu-PBL- NOD-scid mice. Our results suggest that the genetic background, including innate immunity, is critical in the development of primary HIV-1 viremia and subsequent central nervous system invasion with HIV-1. The hu-PBL-NOD-scid mouse represents a useful model for the study of the pathogenesis of HIV-1 in vivo, especially brain involvement, and therapy of primary HIV-1 viremia.

Original languageEnglish
Pages (from-to)2417-2424
Number of pages8
JournalJournal of virology
Volume71
Issue number3
DOIs
Publication statusPublished - Mar 1997

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Koyanagi, Y., Tanaka, Y., Kira, J. I., Ito, M., Hioki, K., Misawa, N., Kawano, Y., Yamasaki, K., Tanaka, R., Suzuki, Y., Ueyama, Y., Terada, E., Tanaka, T., Miyasaka, M., Kobayashi, T., Kumazawa, Y., & Yamamoto, N. (1997). Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain. Journal of virology, 71(3), 2417-2424. https://doi.org/10.1128/jvi.71.3.2417-2424.1997