Publications by authors named "R K Akkina"

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.

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HIV-1 emerged from SIVcpz evolving in humans. Humanized mice are an effective tool for assessing viral evolution via measuring viral loads, CD4 T cell decline, and analyzing genetic changes. Four serial passages showed many non-synonymous mutations important for the adaptation and evolution of SIVcpz to human immune cells.

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Article Synopsis
  • The HIV-2 Group F virus, traced back to non-human primates (NHPs), was found in only two individuals.
  • When this virus was passed through humanized mice, it resulted in higher viral loads and a decline in CD4 T cells, indicating its harmful impact on the immune system.
  • The virus also demonstrated genetic changes that suggest it has the potential to evolve and spread further among humans.
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Introduction: Immunocompetent and immunocompromised murine models have been instrumental in answering important questions regarding ZIKV pathogenesis and vertical transmission. However, mimicking human congenital zika syndrome (CZS) characteristics in these murine models has been less than optimal and does not address the potential viral effects on the human immune system.

Methods: Here, we utilized neonatal humanized Rag2γc mice to model CZS and evaluate the potential viral effects on the differentiation of human hematopoietic stem cells .

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Article Synopsis
  • Serial passage of the SIVmac239 virus helps scientists learn about the genetic changes that enable it to jump from monkeys to humans.
  • Research using humanized mice demonstrates that SIVmac239 continues to evolve with adaptive mutations through four cycles of passage.
  • This study observes a consistent decline in CD4 T cells and an increase in viral loads as SIVmac239 is passed serially, indicating the virus's adaptation process.
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