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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1491481

A dual-purpose humanized mouse model for testing antiviral strategies against both SIV and HIV

Provisionally accepted
Ella Barnett Ella Barnett Snehal Kaginkar Snehal Kaginkar Kmberly Schmitt Kmberly Schmitt Leila Remling-Mulder Leila Remling-Mulder Ramesh Akkina Ramesh Akkina *
  • Colorado State University, Fort Collins, United States

The final, formatted version of the article will be published soon.

    Nonhuman primate (NHP) models employing simian/simian-human immunodeficiency viruses (SIV/SHIVs) played a major role in the study of HIV pathogenesis, latency, and cure studies in a preclinical setting. However, it took many years to arrive at the current effective triple drug ARV regimen against SIV due to the genetic differences with that of HIVs. Since new combinations of drugs will be used in the evolving HIV cure studies, a small animal model would be ideal to determine their efficacy against the commonly used SIVs such as SIVmac239 to triage ineffective drugs prior to their application in NHPs. We recently determined that humanized mice (hu-mice) with a transplanted human immune system are permissive to SIVmac strains in addition to HIVs. Based on this novel finding, here we evaluated the utility of this dual-purpose hu-mouse model to test different ART regimens against SIVmac239. Infected mice showing chronic viremia were treated with a combination anti-retroviral treatment (cART) regimen consisting of of FTC/EVG/TDF (emtricitabine/elvitegravir/tenofovir disoproxil fumarate (FTC/EVG/TDF)). Full viral suppression was seen for several weeks in SIVmac239-infected and treated mice similar to that seen with the HIV-1 BaL virus used as a control. However, viral rebound was eventually observed in SIVmac239 infected mice during the treatment period, suggesting viral escape compared to HIV-1 BaL with which viral suppression was fully sustained. Next, a cART regimen consisting of emtricitabine/bictegravir/tenofovir alafenamide fumarate (FTC/BIC/TAF) was similarly evaluated. Our results showed that this ARV regimen was fully effective in rapidly suppressing both SIVmac239 and HIV-1 BaL. Complete viral suppression was maintained until treatment interruption after which viral loads rebounded. These findings highlight the utility of humanized mice for in vivo screening of new combinations of ARV compounds against various SIVs prior to employing them in NHPs. In addition to identifying new effective cART regimens against SIVs, this model would also be amenable to evaluating immunotherapeutic strategies using broadly neutralizing antibodies, LRAs and novel therapeutics in comparative cure studies of SIV and HIV.

    Keywords: A dual-purpose hu-mouse model for HIV and SIV drug testing, Anti-retroviral drug evaluation against SIV and HIV in humanized mice, A small animal model for SIV, Emtricitabine/elvitegravir/tenofovir disoproxil fumarate (FTC/EVG/TDF) treatment for SIVmac239, Emtricitabine/bictegravir/tenofovir alafenamide fumarate (FTC/BIC/TAF) treatment for SIVmac239, cART evaluations on SIV and HIV in humanized mice, NHPs and humanized mouse models for antiviral drug testing, Humanized mice for HIV cure studies.

    Received: 04 Sep 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Barnett, Kaginkar, Schmitt, Remling-Mulder and Akkina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ramesh Akkina, Colorado State University, Fort Collins, United States

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