Early phase dynamics of traceable mCherry fluorescent protein-carrying HIV-1 infection in human peripheral blood mononuclear cells-transplanted NOD/SCID/Jak3-/- mice

Nobuyo Higashi-Kuwata; Hiromi Ogata-Aoki; Shin-Ichiro Hattori; Hironori Hayashi; Matthew Danish; Manabu Aoki; Chiemi Shiotsu; Tatsuyoshi Kawamura; Hironobu Ihn; Hisataka Kobayashi; Seiji Okada; Hiroaki Mitsuya

doi:10.1016/j.antiviral.2017.03.027

Early phase dynamics of traceable mCherry fluorescent protein-carrying HIV-1 infection in human peripheral blood mononuclear cells-transplanted NOD/SCID/Jak3^-/- mice

Antiviral Res. 2017 Aug:144:83-92. doi: 10.1016/j.antiviral.2017.03.027. Epub 2017 Apr 7.

Authors

Affiliations

¹ Experimental Retrovirology Section, Department of Refractory Viral Infection, National Center for Global Health and Medicine Research Institute, Tokyo, Japan; Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Biomedical Sciences, Japan.
² Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Biomedical Sciences, Japan; Experimental Retrovirology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³ Experimental Retrovirology Section, Department of Refractory Viral Infection, National Center for Global Health and Medicine Research Institute, Tokyo, Japan; Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
⁴ Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Biomedical Sciences, Japan.
⁵ Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Biomedical Sciences, Japan; Experimental Retrovirology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Japan.
⁶ Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
⁷ Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
⁸ Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁹ Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
¹⁰ Experimental Retrovirology Section, Department of Refractory Viral Infection, National Center for Global Health and Medicine Research Institute, Tokyo, Japan; Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Biomedical Sciences, Japan; Experimental Retrovirology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: hmitsuya@helix.nih.gov.

Abstract

We attempted to elucidate early-phase dynamics of HIV-1 infection using replication-competent, red-fluorescent-protein (mCherry)-labeled HIV-1_JR-FL (HIV_JR-FL^mC) and NOD/SCID/Jak3^-/- mice transplanted with Individual-A's human peripheral blood mononuclear cells (hPBMC)(hNOJ mice). On day 7 following HIV_JR-FL^mC inoculation, mCherry-signal-emitting infection foci were readily identified in the subserosa of 10 of 10 HIV_JR-FL^mC-inoculated hNOJ mice, although infection foci were not located without the mCherry signal in unlabeled HIV-1_JR-FL-inoculated mice (n = 6). Even on day 14, infection foci were hardly located in the unlabeled HIV-1_JR-FL-inoculated mice, while in all of 7 HIV_JR-FL^mC-inoculated hNOJ mice examined, mCherry-signal-emitting lymph nodes were easily identified, in which active viral replication was present. On day 14, a significantly larger number of mesenteric lymph nodes were seen in HIV_JR-FL^mC-exposed hNOJ mice than in HIV_JR-FL^mC-unexposed mice (P = 0.0025). The weights of mesenteric lymph nodes of those HIV_JR-FL^mC-exposed hNOJ mice were also greater than those of HIV_JR-FL^mC-unexposed mice (P = 0.0005). When hNOJ mice were inoculated with HIV_JR-FL^mC-exposed hPBMC from Individual-B, significantly greater viremia was seen than in cell-free HIV_JR-FL^mC-inoculated hNOJ mice as examined on day 7. In the lymph nodes of those mice inoculated with HIV_JR-FL^mC-exposed hPBMC from Individual-B, a substantial number of Individual-B's HIV_JR-FL^mC-infected cells were identified together with Individual-A's cells as examined on day 14. The present HIV_JR-FL^mC-infected mouse model represents the first system reported using traceable HIV_JR-FL^mC and human target cells, not using SIV or simian cells, which should be of utility in studies of early-phases of HIV-1 transmission and in evaluating the effects of potential agents for post-exposure and pre-exposure prophylaxis.

Keywords: Cell-associated HIV infection; Early phase dynamics; HIV propagation; In vivo imaging.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Genes, Reporter
HIV Infections / virology*
HIV-1 / genetics
HIV-1 / growth & development*
Janus Kinase 3 / deficiency
Leukocytes, Mononuclear / virology*
Luminescent Proteins / analysis*
Luminescent Proteins / genetics
Lymph Nodes / pathology
Lymph Nodes / virology
Mice
Mice, Inbred NOD
Mice, SCID
Red Fluorescent Protein
Staining and Labeling

Substances

Luminescent Proteins
Jak3 protein, mouse
Janus Kinase 3

Grants and funding

Z01 SC006738/ImNIH/Intramural NIH HHS/United States