Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection

نویسندگان

  • Jiang Deng
  • Jun Xiao
  • Ping Ma
  • Bo Gao
  • Feng Gong
  • Liping Lv
  • Yanyu Zhang
  • Jinbo Xu
چکیده

Cytomegalovirus (CMV) infection leads to notable morbidity and mortality in immunosuppressed patients. Current antiviral drugs are effective but seriously limited in their long-term use due to their relatively high toxicity. In the present study, we characterized the expression of murine CMV microRNAs (MCMV miRNAs) both in vitro and in vivo. Although 29 miRNAs were detectable during in vitro infection, only 11 miRNAs (classified as Group 1) were detectable during in vivo infection, and as many as 18 viral miRNAs (classified as Group 2) were less detectable (<50% of animals) in both the liver and lungs. In addition, viral miRNA profiles in the blood revealed unstable and reduced expression. We next explored the in vitro effects of viral miRNAs on MCMV replication. The inhibition of Group 1 viral miRNAs had little effect on virus production, but transfected cells overexpressing miR-m01-3-5p, miR-M23-1-5p, miR-M55-1, and miR-m107-1-5p in Group 2 showed statistically lower viral loads than those transfected with control miRNA (29%, 29%, 39%, and 43%, respectively, versus control). Finally, we performed hydrodynamic injection of viral miRNA agomirs and observed lower levels of MCMV recurrence in the livers of animals overexpressing the miR-m01-3-5p or mcmv-miR-M23-1-5p agomirs compared with those of animals transfected with control agomir, confirming the antiviral effects of viral miRNA manipulation in vivo. Therefore, the manipulation of viral miRNA expression shows great therapeutic potential and represents a novel antiviral strategy for the miRNA-based treatment of cytomegalovirus infection.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Antiviral agents for preventing cytomegalovirus infection in pediatric renal transplant recipients: A systematic review

Background and Objective: Cytomegalovirus (CMV) infections are associated with severe morbidity and mortality in patients, especially pediatric renal transplantation patients. The use of immunosuppressive agents places these patients at the risk of viral infections. As cytomegalovirus infection influences the graft outcome, adopting useful strategies for limiting this virus after transplantatio...

متن کامل

تب و نوتروپنی به‌علت سیتومگالوویروس به‌دنبال شیمی‌درمانی سرطان پستان: گزارش موردی

Background: Fever in neutropenic patients is a medical emergency which may happen in patients undergoing chemotherapy. The definition of neutropenia varies from institution to institution but is usually defined as an absolute neutrophil count (ANC) < 500 cells/l or < 1,000 cells/l with a predicted nadir of < 500 cells/l. Bacterial and fungal infections are the most important in neutropenic pat...

متن کامل

Cytomegalovirus Infection and Atherosclerosis: A Systematic Review

Cytomegalovirus (CMV) infection is one of the most common infections that affects humans’ cardiovascular system. Although the literature includes controversial evidence for any correlation between CMV infection and arterial atherosclerosis, the majority of studies, especially those with larger patient population and stronger data stand for such a relationship. However, the number of prospective...

متن کامل

Evaluation of Potential Antiviral Activity of the Hydroalcoholic Extract of Lemon Balm L. against Herpes Simplex Virus Type 1

Background and Aims: Lemon Balm L (Lamiaceae) has been used in a variety of practical applications in medical sciences. Its antiviral activity against herpes simplex virus type-1 (HSV-1) was investigated in cell culture. Lemon Balm hydroalcoholic extract was found to be non-toxic to Vero cells up to concentration 800 ug/ml and inhibited the growth and development of HSV-1 in dose-dependent mann...

متن کامل

Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs.

Although the functional parameters of microRNAs (miRNAs) have been explored in some depth, the roles of these molecules in viral infections remain elusive. Here we report a general method for global analysis of miRNA function that compares the significance of both overexpressing and inhibiting each mouse miRNA on the growth properties of different viruses. Our comparative analysis of representa...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2017