Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection.
The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/AR...
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2011
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oai:doaj.org-article:4c8fabced8a44a2fb77a11e4c7dc3be62021-11-18T07:00:41ZSynonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection.1932-620310.1371/journal.pone.0015871https://doaj.org/article/4c8fabced8a44a2fb77a11e4c7dc3be62011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21283512/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/ARFP antibodies in HCV-positive blood donors from Cambodia, using peptide and recombinant protein-based ELISAs. We detected unusual serological profiles in 3 out of 58 HCV positive plasma of genotype 1a. These patients were negative for anti-core antibodies by commercial and peptide-based assays using C-terminal fragments of core but reacted by Western Blot with full-length core protein. All three patients had high levels of anti-core+1/ARFP antibodies. Cloning of the cDNA that corresponds to the core-coding region from these sera resulted in the expression of both core and core+1/ARFP in mammalian cells. The core protein exhibited high amino-acid homology with a consensus HCV1a sequence. However, 10 identical synonymous mutations were found, and 7 were located in the aa(99-124) region of core. All mutations concerned the third base of a codon, and 5/10 represented a T>C mutation. Prediction analyses of the RNA secondary structure revealed conformational changes within the stem-loop region that contains the core+1/ARFP internal AUG initiator at position 85/87. Using the luciferase tagging approach, we showed that core+1/ARFP expression is more efficient from such a sequence than from the prototype HCV1a RNA. We provide additional evidence of the existence of core+1/ARFP in vivo and new data concerning expression of HCV core protein. We show that HCV patients who do not produce normal anti-core antibodies have unusually high levels of anti-core+1/ARFP and harbour several identical synonymous mutations in the core and core+1/ARFP coding region that result in major changes in predicted RNA structure. Such HCV variants may favour core+1/ARFP production during HCV infection.Agata BudkowskaAthanassios KakkanasEric NerrienetOlga KalininaPatrick MaillardSrey Viseth HormGeena DalagiorgouNiki VassilakiUrania GeorgopoulouMichelle MartinotAmadou Alpha SallPenelope MavromaraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e15871 (2011) |
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Medicine R Science Q |
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Medicine R Science Q Agata Budkowska Athanassios Kakkanas Eric Nerrienet Olga Kalinina Patrick Maillard Srey Viseth Horm Geena Dalagiorgou Niki Vassilaki Urania Georgopoulou Michelle Martinot Amadou Alpha Sall Penelope Mavromara Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. |
| description |
The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/ARFP antibodies in HCV-positive blood donors from Cambodia, using peptide and recombinant protein-based ELISAs. We detected unusual serological profiles in 3 out of 58 HCV positive plasma of genotype 1a. These patients were negative for anti-core antibodies by commercial and peptide-based assays using C-terminal fragments of core but reacted by Western Blot with full-length core protein. All three patients had high levels of anti-core+1/ARFP antibodies. Cloning of the cDNA that corresponds to the core-coding region from these sera resulted in the expression of both core and core+1/ARFP in mammalian cells. The core protein exhibited high amino-acid homology with a consensus HCV1a sequence. However, 10 identical synonymous mutations were found, and 7 were located in the aa(99-124) region of core. All mutations concerned the third base of a codon, and 5/10 represented a T>C mutation. Prediction analyses of the RNA secondary structure revealed conformational changes within the stem-loop region that contains the core+1/ARFP internal AUG initiator at position 85/87. Using the luciferase tagging approach, we showed that core+1/ARFP expression is more efficient from such a sequence than from the prototype HCV1a RNA. We provide additional evidence of the existence of core+1/ARFP in vivo and new data concerning expression of HCV core protein. We show that HCV patients who do not produce normal anti-core antibodies have unusually high levels of anti-core+1/ARFP and harbour several identical synonymous mutations in the core and core+1/ARFP coding region that result in major changes in predicted RNA structure. Such HCV variants may favour core+1/ARFP production during HCV infection. |
| format |
article |
| author |
Agata Budkowska Athanassios Kakkanas Eric Nerrienet Olga Kalinina Patrick Maillard Srey Viseth Horm Geena Dalagiorgou Niki Vassilaki Urania Georgopoulou Michelle Martinot Amadou Alpha Sall Penelope Mavromara |
| author_facet |
Agata Budkowska Athanassios Kakkanas Eric Nerrienet Olga Kalinina Patrick Maillard Srey Viseth Horm Geena Dalagiorgou Niki Vassilaki Urania Georgopoulou Michelle Martinot Amadou Alpha Sall Penelope Mavromara |
| author_sort |
Agata Budkowska |
| title |
Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. |
| title_short |
Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. |
| title_full |
Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. |
| title_fullStr |
Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. |
| title_full_unstemmed |
Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. |
| title_sort |
synonymous mutations in the core gene are linked to unusual serological profile in hepatitis c virus infection. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/4c8fabced8a44a2fb77a11e4c7dc3be6 |
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