Publication Date:
2014-12-06
Description:
Background: Hematopoietic stem cell (HSC) transplantation remains the only clinically observed path to functional cure of HIV infection. To better understand the mechanism of HSC-driven HIV control, and apply this therapy to a greater number of patients, we have developed a model of combination antiretroviral therapy (cART)-suppressed HIV infection in the pigtailed macaque, applicable to both gene therapy- and allogeneic transplant-based cure strategies. Following transplantation of HIV-resistant, autologous cells into conditioned animals, we are evaluating the extent to which protected cell progeny impede infection by SIV/HIV (SHIV) chimeric virus in vivo. Methods: Animals are challenged with SHIV virus containing an HIV envelope, after which a 3-drug cART regimen is initiated. Autologous HSCs are engineered to resist infection through targeted disruption of the CCR5 genetic locus using Zinc Finger Nucleases (ZFNs). Engraftment, persistence, and SHIV response of these autologous stem cells, and stem cell-derived lymphoid and myeloid cells, are measured in vivo. Results: SHIV infection in the pigtailed macaque model results in sustained viremia with consequent reduction in CD4+ T cells. Moreover, administration of three-drug cART leads to rapid and durable suppression of plasma viremia to
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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