title: Early phase dynamics of traceable mCherry fluorescent protein-carrying HIV-1 infection in human peripheral blood mononuclear cells-transplanted NOD/SCID/Jak3-/-mice.
abstract: We attempted to elucidate early-phase dynamics of HIV-1 infection using replication-competent, red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL(HIVJR-FLmC) and NOD/SCID/Jak3-/-mice transplanted with Individual-A's human peripheral blood mononuclear cells (hPBMC)(hNOJ mice). On day 7 following HIVJR-FLmCinoculation, mCherry-signal-emitting infection foci were readily identified in the subserosa of 10 of 10 HIVJR-FLmC-inoculated hNOJ mice, although infection foci were not located without the mCherry signal in unlabeled HIV-1JR-FL-inoculated mice (n = 6). Even on day 14, infection foci were hardly located in the unlabeled HIV-1JR-FL-inoculated mice, while in all of 7 HIVJR-FLmC-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 HIVJR-FLmC-exposed hNOJ mice than in HIVJR-FLmC-unexposed mice (P = 0.0025). The weights of mesenteric lymph nodes of those HIVJR-FLmC-exposed hNOJ mice were also greater than those of HIVJR-FLmC-unexposed mice (P = 0.0005). When hNOJ mice were inoculated with HIVJR-FLmC-exposed hPBMC from Individual-B, significantly greater viremia was seen than in cell-free HIVJR-FLmC-inoculated hNOJ mice as examined on day 7. In the lymph nodes of those mice inoculated with HIVJR-FLmC-exposed hPBMC from Individual-B, a substantial number of Individual-B's HIVJR-FLmC-infected cells were identified together with Individual-A's cells as examined on day 14. The present HIVJR-FLmC-infected mouse model represents the first system reported using traceable HIVJR-FLmCand 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.
authors.affiliation: 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.
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Higashi-Kuwata
authors.affiliation: 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.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ogata-Aoki
authors.affiliation: 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.
authors.forename: Shin-Ichiro
authors.initials: SI
authors.lastname: Hattori
authors.affiliation: 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.
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Biomedical Sciences, Japan.
authors.forename: Matthew
authors.initials: M
authors.lastname: Danish
authors.affiliation: 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.
authors.forename: Manabu
authors.initials: M
authors.lastname: Aoki
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Chiemi
authors.initials: C
authors.lastname: Shiotsu
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Tatsuyoshi
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.affiliation: 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.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuya
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017930:Genes, Reporter; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D053616:Janus Kinase 3 / Q000172:deficiency; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008164:Luminescent Proteins / Q000032:analysis* / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013194:Staining and Labeling; D000097573:Red Fluorescent Protein
chemical_list: D053616:Janus Kinase 3; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C507935:Jak3 protein, mouse
keywords: Cell-associated HIV infection; Early phase dynamics; HIV propagation; In vivo imaging