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Updated: Feb 25, 2026
Humanized NOG Mice for Intravaginal HIV Exposure and Treatment of HIV Infection
Published on: January 31, 2020
Modeling the evolution of SIV sooty mangabey progenitor virus towards HIV-2 using humanized mice
Kimberly Schmitt1, Dipu Mohan Kumar1, James Curlin1
1Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Abstract:
HIV-2 is thought to have originated from an SIV progenitor native to sooty mangabeys. To model the initial human transmission and understand the sequential viral evolution, humanized mice were infected with SIVsm and serially passaged for five generations. Productive infection was seen by week 3 during the initial challenge followed by chronic viremia and gradual CD4+ T cell decline. Viral loads increased by the 5th generation resulting in more rapid CD4+ T cell decline. Genetic analysis revealed several amino acid substitutions that were nonsynonymous and fixed in multiple hu-mice across each of the 5 generations in the nef, env and rev regions. The highest rate of substitution occurred in the nef and env regions and most were observed within the first two generations. These data demonstrated the utility of hu-mice in modeling the SIVsm transmission to the human and to evaluate its potential sequential evolution into a human pathogen of HIV-2 lineage.
Insights
Humanized mice infected with SIVsm showed productive infection and CD4+ T cell decline, mimicking HIV-2 origins. Viral evolution in mice revealed key genetic changes, aiding study of human pathogen development.
Area of Science:
- Virology
- Immunology
- Primate Retroviruses
Background:
- Human Immunodeficiency Virus type 2 (HIV-2) is believed to have evolved from Simian Immunodeficiency Virus (SIV) found in sooty mangabeys.
- Understanding the initial transmission and subsequent viral evolution is crucial for modeling HIV-2 origins and pathogenesis.
Purpose of the Study:
- To model the initial human transmission of SIVsm.
- To investigate the sequential viral evolution of SIVsm in a humanized mouse model.
- To evaluate the potential of SIVsm to evolve into a human pathogen similar to HIV-2.
Main Methods:
- Humanized mice were infected with SIVsm (SIV from sooty mangabeys).
- Mice were serially passaged for five generations to observe viral adaptation and evolution.
- Viral loads, CD4+ T cell counts, and genetic sequences (nef, env, rev regions) were analyzed across generations.
Main Results:
- Productive infection and chronic viremia were observed, accompanied by a gradual decline in CD4+ T cells.
- Viral loads increased by the 5th generation, leading to a more accelerated CD4+ T cell depletion.
- Key nonsynonymous amino acid substitutions fixed in viral genes (nef, env, rev) were identified, particularly within the first two generations.
Conclusions:
- Humanized mice effectively model SIVsm transmission and initial human adaptation.
- The study demonstrates SIVsm's capacity for sequential evolution in vivo.
- Findings provide insights into the evolutionary pathway toward HIV-2 lineage.
