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. 2013;8(4):e60621.
doi: 10.1371/journal.pone.0060621. Epub 2013 Apr 3.

Humans have antibodies against a plant virus: evidence from tobacco mosaic virus

Ruolan Liu  1 , Radhika A Vaishnav, Andrew M Roberts, Robert P Friedland
Affiliations

Humans have antibodies against a plant virus: evidence from tobacco mosaic virus

Ruolan Liu et al. PLoS One. 2013.

Abstract

Tobacco mosaic virus (TMV), a widespread plant pathogen, is found in tobacco (including cigarettes and smokeless tobacco) as well as in many other plants. Plant viruses do not replicate or cause infection in humans or other mammals. This study was done to determine whether exposure to tobacco products induces an immune response to TMV in humans. Using a sandwich ELISA assay, we detected serum anti-TMV antibodies (IgG, IgG1, IgG3, IgG4, IgA, and IgM) in all subjects enrolled in the study (20 healthy smokers, 20 smokeless-tobacco users, and 20 non-smokers). Smokers had a higher level of serum anti-TMV IgG antibodies than non-smokers, while the serum level of anti-TMV IgA from smokeless tobacco users was lower than smokers and non-smokers. Using bioinformatics, we also found that the human protein TOMM40L (an outer mitochondrial membrane 40 homolog--like translocase) contains a strong homology of six contiguous amino acids to the TMV coat protein, and TOMM40L peptide exhibited cross-reactivity with anti-TMV antibodies. People who smoke cigarettes or other tobacco products experience a lower risk of developing Parkinson's disease, but the mechanism by which this occurs is unclear. Our results showing molecular mimicry between TMV and human TOMM40L raise the question as to whether TMV has a potential role in smokers against Parkinson's disease development. The potential mechanisms of molecular mimicry between plant viruses and human disease should be further explored.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Effects of tobacco-smoke and smokeless-tobacco exposure on serum anti-Tobacco Mosaic Virus (TMV) IgG.
Sera were obtained from groups of smoke tobacco users (smokers), smokeless tobacco users (tobacco chewers) and non-tobacco users (n  =  20/group). Serum anti-TMV IgG levels were measured by a customized sandwich ELISA assay. The serum dilution factor was 1∶100 and the data is expressed as O.D. value (mean ± SE). All data are representative of two to three assays with similar results. (A) Serum anti-TMV IgG in whole study population; (B) Ethnic characteristics of the study population; (C) Serum anti-TMV IgG in African American study population; and (D) Serum anti-TMV IgG in Caucasian study population. p-value, Student’s t test, *p < 0.05.
Figure 2
Figure 2. Effects of tobacco-smoke and smokeless-tobacco exposure on serum anti-TMV IgA, IgM, IgD and IgE.
Sera were obtained from groups of smokers, smokeless tobacco users and non-tobacco users (n = 20/group). Serum anti-TMV IgA, IgM, IgD, and IgE levels were measured by a customized sandwich ELISA assay. The serum dilution factors were 1∶50 for anti-TMV IgA and IgM and 1∶5 for anti-TMV IgD and IgE. Data is expressed as O.D. values (mean ± SE). All data are representative of two to three assays with similar results. (A) Serum anti-TMV IgA in whole study population; (B) Serum anti-TMV IgM in whole study population; (C) Serum anti-TMV IgD in whole study population; (D) Serum anti-TMV IgG in whole study population. p-value, ANOVA, *p < 0.05.
Figure 3
Figure 3. Cross reactivity between TMV and TOMM40L.
(A) Sequence homology comparison among TMV-Vulgare coat protein. Basic Local Alignment Search Tool (BLAST) indicated the regions of local sequence similarity (color red) among TMV and TOMM40L gene and TOMM40L peptide; and sequence similarity (color green) between TOMM40L gene and peptide. (B) Cross-reactivity of anti-TMV antibodies and TOMM40L peptide determined by tobacco mosaic virus PathoScreen ELISA kit. Data are representative of two independent experiments with similar results. Results were expressed as O.D. values (mean ± SE, triple wells per group). Tom40  =  TOMM40L peptide, Mito  =  crude mitochondria pellet, TMV (+)  =  TMV-infected tobacco leaf, TMV (-)  =  TMV-negative alstroemeria leaf, and control  =  ELISA assay buffer.
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