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Updated: Sep 16, 2026
Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
Early phase dynamics of traceable mCherry fluorescent protein-carrying HIV-1 infection in human peripheral blood
Nobuyo Higashi-Kuwata1, Hiromi Ogata-Aoki2, Shin-Ichiro Hattori3
1Experimental 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.
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-FLmC inoculation, 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-FLmC 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.
Insights
This study developed a traceable humanized mouse model for early HIV-1 infection dynamics. The model successfully visualized HIV-1 transmission and replication in lymph nodes, aiding prophylaxis research.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Understanding early-phase dynamics of Human Immunodeficiency Virus type 1 (HIV-1) infection is crucial for developing effective prevention and treatment strategies.
- Previous models often relied on simian immunodeficiency virus (SIV) or simian cells, limiting direct relevance to human HIV-1 infection.
Purpose of the Study:
- To elucidate early-phase dynamics of HIV-1 infection using a novel, traceable humanized mouse model.
- To establish a system for studying HIV-1 transmission and evaluating prophylactic agents without using SIV or simian cells.
Main Methods:
- Utilized replication-competent, red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL (HIVJR-FLmC) in NOD/SCID/Jak3-/- mice transplanted with human peripheral blood mononuclear cells (hPBMC) (hNOJ mice).
- Visualized infection foci via mCherry signal in subserosa and lymph nodes on days 7 and 14 post-inoculation.
- Compared infection dynamics between HIVJR-FLmC-inoculated and unlabeled HIV-1JR-FL-inoculated hNOJ mice, and assessed viremia and lymph node changes.
Main Results:
- mCherry-signal-emitting infection foci were readily identified in hNOJ mice inoculated with HIVJR-FLmC by day 7, with active viral replication observed in lymph nodes by day 14.
- HIVJR-FLmC-exposed hNOJ mice showed significantly increased mesenteric lymph node number and weight compared to controls.
- Inoculation with HIVJR-FLmC-exposed hPBMC resulted in greater viremia and detectable infected cells in lymph nodes.
Conclusions:
- The developed HIVJR-FLmC-infected hNOJ mouse model is the first reported system using traceable HIV-1 and human target cells for studying early infection phases.
- This model provides a valuable tool for investigating early HIV-1 transmission dynamics and evaluating post-exposure and pre-exposure prophylaxis agents in a human-relevant context.
