اثر جهش های گریز بر پایداری آنتی ژن سطحی S در مبتلایان به هپاتیت B مزمن

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه بیوتکنولوژی، دانشگاه آزاد اسلامی، واحد علوم تحقیقات

2 دانشیار، ژنتیک مولکولی، موسسه تحقیقات واکسن و سرم سازی رازی، سازمان تحقیقات، آموزش و ترویج کشاورزی، کرج، ایران

3 موسسه تحقیقات واکسن و سرم سازی رازی، سازمان تحقیقات، آموزش و ترویج کشاورزی

چکیده

مقدمه: سویه‌های جهش یافته مقاوم به آنالوگ‌های نوکلئوزیدی/نوکلئوتیدی ویروس هپاتیت B (HBV) در نتیجه طولانی شدن زمان مصرف و بروز پلی-مرفیسم تک نوکلئوتیدی (SNP) و جهش‌های گریز پدیدار می‌شوند. هدف از مطالعه حاضر ، شناسایی فشارهای انتخابی و جهش فرار ایمنی در ژن HBsAg (S) در بیماران مبتلا به HBV مزمن است.
مواد و روش ها: در این مطالعه مقطعی که در سال 1397 در شهر کرج انجام شد، پنجاه بیمار مبتلا به هپاتیت B مزمن در دو گروه تحت درمان و بدون درمان دسته‌بندی شدند. تعداد کپی‌های DNA ویروس هر بیمار با real time PCR برآورد شده و توالی ژن S تعیین شد. اثر هر SNP بر پایداری پروتئین S با I-mutant و برآورد میزان انرژی آزاد DDG پیش بینی شد.
یافته ها: کمترین میزان بار ویروس و بیشترین آن به ترتیب 101 × 1/1 و ml/108 × 3/4 کپی برآورد شد. بیشترین تعداد جهش منجر به تغییر شامل Q101R، T115N، S143L، و Q129P در یک فرد با سابقه مصرف دارو تعیین شد. در یک بیمار بدون درمان، جهش های M133T و L175S مشاهده شد. جهش Q129P، S174N و Y134C نیز در افراد دیگر با سابقه درمان مشاهده شد. از مجموع 8 تغییر اسید آمینه، L175S با DDG برابر با Kcal/mol 87/1- بیشترین اثر کاهشی را بر پایداری پروتئین S داشت.
نتیجه گیری: براساس این داده ها، بین SNP ژن S ویروس و پیدایش جهش گریز ارتباط وجود دارد. یافته‌های بررسی‌های جهش‌های گریز می تواند بر بهبود درمان و ایمن سازی علیه عفونت مزمن هپاتیت B اثر گذار باشد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

Effect of the escape mutations on surface antigen S stability in chronic hepatitis B patients

نویسندگان [English]

  • Niloufar Rezaee 1
  • Shahla Shahsavandi 2
  • Mohammad Reza Samiee 3
1 Biotechnology, Islamic Azad University, Science and Research Branch
2 Associated professor, Molecular genetics, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization, Karaj, Iran
3 Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization
چکیده [English]

Background: Mutant strains resistant to nucleoside/nucleotide analogs of hepatitis B virus (HBV) emerge due to the prolonged usage and single nucleotide polymorphism (SNP) incidence and escape mutations. The current study aimed to detect the selective pressures and the immune-associated escape mutation in HBsAg (S) gene in chronically HBV-infected patients.
Materials and Methods: In this cross-sectional study in 2013, fifty patients with chronic hepatitis B in Karaj were divided into treated and untreated groups. The number of virus DNA copies was quantified by real-time PCR and S gene was sequenced. The effect of each SNP on S protein stability was predicted with 1-mutant and DDG free energy estimation.
Results: The lowest and the highest viral load in the serum samples were estimated 1.1 × 101/ml and 4.3 × 108/ml copies, respectively. The highest number of mutations leading to amino acid substitution includes Q101R, T115N, S143L, and Q129P was determined in one person who used drug was identified. In one patient without treatment, the M133T and L175S mutations were observed. The Q129P, S174N, and Y134C were also seen in others with a history of treatment. Of the 8 amino acid changes, L175S with DDG equal to 1.87 Kcal/mol had the greatest reduction effect on S protein stability.
Conclusion: According to these data, there is a relationship between the SNP of the virus S gene and the emergence of escape mutations. Findings of studies of escape mutations in human populations can influence the improvement of treatment and immunization against chronic hepatitis B infection.

کلیدواژه‌ها [English]

  • chronic hepatitis B infection
  • escape mutation
  • S gene
  • single nucleotide polymorphism

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مجله دانشکده پزشکی دانشگاه علوم پزشکی مشهد
دوره 67، شماره 3
مرداد-شهریور1403
مرداد و شهریور 1403
صفحه 1070-1081

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