Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells

Authors

• Zhe Yuan, University of Nebraska-LincolnFollow
• Guobin Kang, University of Nebraska–LincolnFollow
• Wuxun Lu, University of Nebraska-Lincoln
• Qingsheng Li, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2017

Citation

Journal of Virus Eradication 2017; 3: 61–65

Comments

© 2017 The Authors.

Abstract

Background: HIV-1 infection remains incurable on antiretroviral therapy (ART) due to virus latency. To date, enhanced co-culture assays, including viral outgrowth assays (VOA), are commonly used to measure HIV-1 latent reservoirs and evaluate latency-reversing agents (LRAs). However, VOA can only reactivate a small fraction of intact proviruses.

Methods: To explore the utility of NOD scid gamma (NSG) mice as an in vivo model to reactivate HIV-1 proviruses from VOA-negative CD4+ T cells, resting CD4+ T cells from an HIV-1 latently infected individual were isolated and the human CD4+ T cells corresponding to VOA-positive and VOA-negative CD4+ T cells were engrafted into NSG mice. Plasma viral load (pVL) and human CD4+ T cells were quantified every other week using qRT-PCR and flow cytometry.

Results: We found that NSG mice reactivated latently infected HIV-1 fromVOA-positive CD4+T cells as well as VOA-negative CD4+ T cells. Engrafted CD4+ T cells proliferated considerably in vivo, peaked prior to provirus reactivation, and lasted for up to 14 weeks. Sequence analyses revealed that reactivated proviruses inVOA-positive andVOA-negative CD4+T cells are different.

Conclusion: Taken together, NSG mice can support long-term engraftment of human CD4+ T cells and reactivate VOA-positive and VOA-negative proviruses. Therefore, this in vivo model has the potential to be used to study the underlying mechanisms of HIV-1 latency and reactivation.