SEQUENCE SIMILARITY BETWEEN THYROID SELF-PROTEIN AND HEPATITIS C VIRUS POLYPROTEIN: possible triggering mechanism of autoimmune thyroiditis

ABSTRACT Background - Exposure to viral antigens that share amino acid sequence similar with self- antigens might trigger autoimmune diseases in genetically predisposed individuals, and the molecular mimicry theory suggests that epitope mimicry between the virus and human proteins can activate autoimmune disease. Objective - The purpose of this study is to explore the possible sequence similarity between the amino acid sequences of thyroid self-protein and hepatitis C virus proteins, using databanks of proteins and immunogenic peptides, to explain autoimmune thyroid disease. Methods - Were performed the comparisons between the amino acid sequence of the hepatitis C virus polyprotein and thyroid self-protein human, available in the database of National Center for Biotechnology Information on Basic Local Alignment Search Tool. Results - The sequence similarity was related each hepatitis C virus genotype to each thyroid antigen. The similarities between the thyroid and the viral peptides ranged from 21.0 % (31 identical residues out of 147 amino acid in the sequence) to 71.0% (5 identical residues out of 7 amino acid in the sequence). Conclusion - Bioinformatics data, suggest a possible pathogenic link between hepatitis C virus and autoimmune thyroid disease. Through of molecular mimicry is observed that sequences similarities between viral polyproteins and self-proteins thyroid could be a mechanism of induction of crossover immune response to self-antigens, with a breakdown of self-tolerance, resulting in autoimmune thyroid disease.

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Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.87.6.2057 ◽

1990 ◽

Vol 87 (6) ◽

pp. 2057-2061 ◽

Cited By ~ 345

Author(s):

R. H. Miller ◽

R. H. Purcell

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Amino Acid ◽

Amino Acid Sequence ◽

Plant Virus ◽

Sequence Similarity ◽

Amino Acid Sequence Similarity

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Prevalence of autoantibodies and the risk of autoimmune thyroid disease in children with chronic hepatitis C virus infection treated with interferon-α

World Journal of Gastroenterology ◽

10.3748/wjg.v12.i36.5787 ◽

2006 ◽

Vol 12 (36) ◽

pp. 5787 ◽

Cited By ~ 18

Author(s):

Stephan Gehring

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Infection ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Interferon Α ◽

Hepatitis C Virus Infection ◽

Autoimmune Thyroid ◽

Chronic Hepatitis C Virus

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S2072 Interferon-Related Autoimmune Thyroid Disease in 3414 Naïve Patients with Chronic Hepatitis C

Gastroenterology ◽

10.1016/s0016-5085(09)61487-6 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-324

Author(s):

Filomena Morisco ◽

Daniela C. Amoruso ◽

Mariateresa Tartaglione ◽

Antonio D. Luna ◽

Pietro Andreone ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Autoimmune Thyroid

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Molecular mimicry and autoimmune thyroid disease

Reviews in Endocrine and Metabolic Disorders ◽

10.1007/s11154-016-9363-2 ◽

2016 ◽

Vol 17 (4) ◽

pp. 485-498 ◽

Cited By ~ 36

Author(s):

Salvatore Benvenga ◽

Fabrizio Guarneri

Keyword(s):

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Molecular Mimicry ◽

Autoimmune Thyroid

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Interferon Resistance of Hepatitis C Virus Genotype 1b: Relationship to Nonstructural 5A Gene Quasispecies Mutations

Journal of Virology ◽

10.1128/jvi.72.4.2795-2805.1998 ◽

1998 ◽

Vol 72 (4) ◽

pp. 2795-2805 ◽

Cited By ~ 140

Author(s):

Jean-Michel Pawlotsky ◽

Georgios Germanidis ◽

Avidan U. Neumann ◽

Muriel Pellerin ◽

Pierre-Olivier Frainais ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Amino Acid ◽

Amino Acid Sequence ◽

Critical Role ◽

Patient Specific ◽

Amino Acid Substitutions ◽

Virus Genotype ◽

Ns5a Protein ◽

Genotype 1B

ABSTRACT A 40-amino-acid sequence located in the nonstructural 5A (NS5A) protein of hepatitis C virus genotype 1b (HCV-1b) was recently suggested to be the interferon sensitivity-determining region (ISDR), because HCV-1b strains with an ISDR amino acid sequence identical to that of the prototype strain HCV-J were found to be resistant to alpha interferon (IFN-α) whereas strains with amino acid substitutions were found to be sensitive (N. Enomoto, I. Sakuma, Y. Asahina, M. Kurosaki, T. Murakami, C. Yamamoto, N. Izumi, F. Marumo, and C. Sato, J. Clin. Invest. 96:224–230, 1995; N. Enomoto, I. Sakuma, Y. Asahina, M. Kurosaki, T. Murakami, C. Yamamoto, Y. Ogura, N. Izumi, F. Marumo, and C. Sato, N. Engl. J. Med. 334:77–81, 1996). We used single-strand conformation polymorphism (SSCP) analysis, combined with cloning and sequencing strategies, to characterize NS5A quasispecies in HCV-1b-infected patients and determine the relationships between pre- and posttreatment NS5A quasispecies mutations and the IFN-α sensitivity of HCV-1b. The serine residues involved in phosphorylation of NS5A protein were highly conserved both in the various patients and in quasispecies in a given patient, suggesting that phosphorylation is important in NS5A protein function. A hot spot for amino acid substitutions was found at positions 2217 to 2218; it could be the result of either strong selection pressure or tolerance to these amino acid replacements. The proportion of synonymous mutations was significantly higher than the proportion of nonsynonymous mutations, suggesting that genetic variability in the region studied was the result of high mutation rates and viral replication kinetics rather than of positive selection. Sustained HCV RNA clearance was associated with low viral load and low nucleotide sequence entropy, suggesting (i) that the replication kinetics when treatment is started plays a critical role in HCV-1b sensitivity to IFN-α and (ii) that HCV-1b resistance to IFN-α could be conferred by numerous and/or related mutations that could be patient specific and located at different positions throughout the viral genome and could allow escape variants to be selected by IFN-α-stimulated immune responses. No NS5A sequence appeared to be intrinsically resistant or sensitive to IFN-α, but the HCV-J sequence was significantly more frequent in nonresponder quasispecies than in sustained virological responder quasispecies, suggesting that the balance between NS5A quasispecies sequences in infected patients could have a subtle regulatory influence on HCV replication.

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The Spectrum of Autoimmune Thyroid Disease in the Short to Medium Term Following Interferon-αTherapy for Chronic Hepatitis C

International Journal of Endocrinology ◽

10.1155/2009/241786 ◽

2009 ◽

Vol 2009 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Huy A. Tran ◽

Glenn E. M. Reeves

Keyword(s):

Hepatitis C ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Interferon Therapy ◽

Pegylated Interferon ◽

Thyroid Diseases ◽

Hepatitis C Infection ◽

Medium Term ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Thyroid

Autoimmune thyroid diseases are common manifestations of hepatitis C infection, exacerbated by interferon-based treatment. However, the occurrence and pattern of thyroid disease in the short/medium term following the completion of IFN-based therapy is relatively unknown and there are very few previous reports regarding the specific spectrum of autoimmune thyroid disease that may follow such therapy. We hereby report 3 cases which demonstrate the range of thyroid diseases that may occur following interferon therapy. The hypothesis advanced is that in the pathogenesis of these conditions there must be both triggering and sustaining mechanisms as thyroid diseases occur well outside the immediate effect window of pegylated interferon. This paper suggests the need to continue thyroid surveillance in IFN-treated HCV patients following the completion of therapy, perhaps for the first 6 months.

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Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2434175100 ◽

2003 ◽

Vol 100 (25) ◽

pp. 15119-15124 ◽

Cited By ~ 123

Author(s):

Y. Ban ◽

D. A. Greenberg ◽

E. Concepcion ◽

L. Skrabanek ◽

R. Villanueva ◽

...

Keyword(s):

Amino Acid ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Amino Acid Substitutions ◽

Autoimmune Thyroid ◽

Thyroglobulin Gene

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Antibody-induced modulation of TSH receptor post-translational processing

Journal of Endocrinology ◽

10.1677/joe-07-0058 ◽

2007 ◽

Vol 195 (1) ◽

pp. 179-186 ◽

Cited By ~ 13

Author(s):

Takao Ando ◽

Rauf Latif ◽

Terry F Davies

Keyword(s):

Amino Acid ◽

Thyroid Function ◽

Thyroid Disease ◽

Antigen Processing ◽

Autoimmune Thyroid Disease ◽

Neutral Type ◽

Tsh Receptor ◽

Neutral Group ◽

Α Subunit ◽

Autoimmune Thyroid

The post-translational processing of the TSH receptor (TSHR) includes intra-molecular cleavage with the loss of a 50 amino acid ectodomain region and the formation of two subunits (α and β), followed by likely α subunit shedding. TSHR antibodies (TSHR-Abs), which are directed at the ectodomain, may influence thyroid function by stimulating or inhibiting TSHR signaling or may bind without any such influence (the neutral group of antibodies). When we examined the characteristics of a series of monoclonal TSHR-Abs, we found that many were able to inhibit receptor cleavage and enhance TSHR expression. This was especially apparent with the neutral type of TSHR-Abs directed to the cleaved region of the ectodomain (aa 316–366). Indeed, such inhibition appeared to be epitope dependent with TSHR-Abs directed to regions after residues 335–354 showing no such activity. We propose that this aberrant process, whereby TSHR-Abs influence antigen processing, is a novel mechanism for the maintenance and exacerbation of autoimmune thyroid disease.

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