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. 2010 Jun 10;6(6):e1000803.
doi: 10.1371/journal.ppat.1000803.

Immunotoxin complementation of HAART to deplete persisting HIV-infected cell reservoirs

Edward A Berger  1 , Ira Pastan
Affiliations

Immunotoxin complementation of HAART to deplete persisting HIV-infected cell reservoirs

Edward A Berger et al. PLoS Pathog. .
No abstract available

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Conflict of interest statement

E.A.B. and I.P. are co-inventors on NIH-owned issued patents and patent applications for CD4-PE and 3B3-PE.

Figures

Figure 1
Figure 1. Schematic of Env-targeted toxins based on Pseudomonas exotoxin A.
The immunotoxins are based on the domain organization of native PE (top). The N-terminal segment (domain I) is involved in binding to a surface receptor (members of the low density lipoprotein receptor-related protein 1 family), the central region (domain II) facilitates membrane translocation of the toxin into the cytoplasm, and the C-terminal segment (domain III) catalyzes ADP-ribosylation of elongation factor 2, resulting in shut-down of protein synthesis and cell death. In the recombinant single chain immunotoxins, domain I is replaced by a targeting moiety directed at HIV-1 gp120: soluble CD4 first two domains (CD4-PE, middle), or the 3B3 SCFv (3B3-PE, bottom).
Figure 2
Figure 2. Effects of complementing HAART with Env-targeted toxins in thy/liv SCID-hu mouse model.
Thy/liv-SCID-hu mice were injected intraperitoneally with HIV and either left untreated (None) or immediately started on the indicated treatment. One month later, the left thy/liv implants were biopsied, and viral loads were analyzed by quantitative coculture (open bars). Drug therapy was then stopped, and after 1 month the left thy/liv implant of each mouse was rebiopsied and the viral load quantitated (filled bars). The data are presented as the TCID/106 thymocytes; the mean values (± SEM) were calculated for each group. Left panel, HAART (zidovudine+ lamivudine + ritonavir) or immunotoxins alone; right panel, HAART alone compared to HAART plus immunotoxins. Data adapted from (© 2000 by Goldstein et al.).
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