Bryodin, a single-chain ribosome-inactivating protein, selectively inhibits the growth of HIV-1-infected cells and reduces HIV-1 production

Wachinger, Michael; Samtleben, Rainer; Gerhäuser, Clarissa; Wagner, Hildebert; Erfle, Volker

doi:10.1007/bf02576205

Cited by 18 publications

(8 citation statements)

References 44 publications

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“…In mammalian cell culture, PAP inhibits the replication of influenza virus (3) and poliovirus (4). Similar results have been found with plant proteins homologous to PAP, including abrin A chain (8), trichosanthin (9), and bryodin (10), that all appear to function like PAP. Diphtheria toxin and Pseudomonas exotoxin A, which enzymatically inactivate protein synthesis differently than the plant toxins, also become more toxic upon viral penetration of cells (11,12).…”

supporting

confidence: 70%

RNase inhibition of human immunodeficiency virus infection of H9 cells.

Youle

Mikulski

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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supporting

confidence: 70%

RNase inhibition of human immunodeficiency virus infection of H9 cells.

Youle

Mikulski

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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“…Also, a precedence of antiviral activity without the B subunit has been set by many plant RIPs. Type 1 RIP hemitoxins composed solely of an enzymatic A chain are potent antiviral agents; examples include inhibition of HIV replication by pokeweed antiviral protein (45), bryodin (56), and trichosanthin (9). Similar anti-HIV activity is exhibited by an isolated A chain of ricin (45).…”

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Shiga Toxin 1: Suppression of Bovine Leukemia Virus-Related Spontaneous Lymphocyte Proliferation

Ferens

Hovde

2000

Infect Immun

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Human infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) cause hemorrhagic colitis. The Stxs belong to a large family of ribosome-inactivating proteins (RIPs) that are found in a variety of higher plants and some bacteria. Many RIPs have potent antiviral activity for the plants that synthesize them. STEC strains, both virulent and nonvirulent to humans, are frequently isolated from healthy cattle. Interestingly, despite intensive investigations, it is not known why cattle carry STEC. We tested the hypothesis that Stx has antiviral properties for bovine viruses by assessing the impact of Stx type 1 (Stx1) on bovine peripheral blood mononuclear cells (PBMC) from cows infected with bovine leukemia virus (BLV). PBMC from BLV-positive animals invariably displayed spontaneous lymphocyte proliferation (SLP) in vitro. Stx1 or the toxin A subunit (Stx1A) strongly inhibited SLP. Toxin only weakly reduced the pokeweed mitogen-or interleukin-2-induced proliferation of PBMC from normal (BLV-negative) cows and had no effect on concanavalin A-induced proliferation. The toxin activity in PBMC from BLV-positive cattle was selective for viral SLP and did not abrogate cell response to pokeweed mitogen-or interleukin-2-induced proliferation. Antibody to virus or Stx1A was most effective at inhibiting SLP if administered at the start of cell culture, indicating that both reagents likely interfere with BLV-dependent initiation of SLP. Stx1A inhibited expression of BLV p24 protein by PBMC. A well-defined mutant Stx1A (E167D) that has decreased catalytic activity was not effective at inhibiting SLP, suggesting the inhibition of protein synthesis is likely the mechanism of toxin antiviral activity. Our data suggest that Stx has potent antiviral activity and may serve an important role in BLV-infected cattle by inhibiting BLV replication and thus slowing the progression of infection to its malignant end stage.

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“…Bryodin has been reported to inhibit the growth of HIVinfected cells and to reduce HIV production (Wachinger et al, 1993). Other RIPs including trichosanthin (McGrath et al, 1989) and GAP31 from Gelonium multiflorum (Lee-Huang et al, 1994) also exhibit anti-HIV properties.…”

Section: Discussionmentioning

confidence: 99%

Molecular, Biological, and Preliminary Structural Analysis of Recombinant Bryodin 1, a Ribosome-Inactivating Protein from the PlantBryonia dioica

Neubauer

et al. 1997

Biochemistry

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Bryonia dioica (Cucurbitaceae family) produces at least two type I ribosome-inactivating proteins, bryodin 1 (BD1) and bryodin 2 (BD2). A cDNA sequence encoding BD1 was isolated from B. dioica leaf mRNA using degenerative oligonucleotides and codes for a 22 amino acid signal peptide followed by a protein of 267 residues. Expression of two recombinant BD1 (rBD1) forms in Escherichia coli yielded proteins of 267 (to the natural stop codon) and 247 amino acids (to the putative cleavage site yielding the mature protein) that had identical protein synthesis inhibition activity as compared to native BD1. The substitution of Lys for Glu at position 189 near the active site reduced the ability of rBD1 to inhibit protein synthesis by 10-fold. Toxicologic analysis showed that rBD1 was well tolerated in rodents with LD50 values of 40 mg/kg in mice and >25 mg/kg in rats. A crystal of mature rBD1 protein was used to collect X-ray diffraction data to 2.1 A resolution. The rBD1 crystal structure was solved and showed extensive homology with other type I RIPs and A chains of type II RIPs. The studies described here demonstrate that rBD1 retains full biologic activity and serve as a guide for using this potent, yet nontoxic, RIP in the construction of single-chain immunotoxin fusion proteins.

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Bryodin, a single-chain ribosome-inactivating protein, selectively inhibits the growth of HIV-1-infected cells and reduces HIV-1 production

Cited by 18 publications

References 44 publications

RNase inhibition of human immunodeficiency virus infection of H9 cells.

RNase inhibition of human immunodeficiency virus infection of H9 cells.

Antiviral Activity of Shiga Toxin 1: Suppression of Bovine Leukemia Virus-Related Spontaneous Lymphocyte Proliferation

Molecular, Biological, and Preliminary Structural Analysis of Recombinant Bryodin 1, a Ribosome-Inactivating Protein from the PlantBryonia dioica

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