Vitamin B12 and Hepatitis C: Molecular Biology and Human Pathology

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2001 Apr 11

PMID 11296247

Citations 15

Authors

W B Lott

S S Takyar

J Tuppen

D H Crawford

M Harrison

T P Sloots

E J Gowans

Affiliations

Soon will be listed here.

Abstract

Cobalamins are stored in high concentrations in the human liver and thus are available to participate in the regulation of hepatotropic virus functions. We show that cyanocobalamin (vitamin B12) inhibited the HCV internal ribosome entry site (IRES)-dependent translation of a reporter gene in vitro in a dose-dependent manner without significantly affecting the cap-dependent mechanism. Vitamin B12 failed to inhibit translation by IRES elements from encephalomyocarditis virus (EMCV) or classical swine fever virus (CSFV). We also demonstrate a relationship between the total cobalamin concentration in human sera and HCV viral load (a measure of viral replication in the host). The mean viral load was two orders of magnitude greater when the serum cobalamin concentration was above 200 pM (P < 0.003), suggesting that the total cobalamin concentration in an HCV-infected liver is biologically significant in HCV replication.

Citing Articles

Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease.

Casas-Deza D, Martinez-Sapina A, Espina S, Garcia-Rodriguez B, Fernandez-Bonilla E, Sanz-Paris A J Clin Med. 2022; 11(14).

PMID: 35887813 PMC: 9315656. DOI: 10.3390/jcm11144049.

Medicinal Animals and Plants as Alternative and Complementary Medicine in Southern Regions of Khyber Pakhtunkhwa, Pakistan.

Mussarat S, Ali R, Ali S, Mothana R, Ullah R, Adnan M Front Pharmacol. 2021; 12:649046.

PMID: 34504421 PMC: 8422074. DOI: 10.3389/fphar.2021.649046.

The Presence of Circulating Nucleated Red Blood Cells Is Associated With Disease Severity in Patients of Hemorrhagic Fever With Renal Syndrome.

Zhang J, Tang K, Zhang Y, Ma Y, Zhang C, Hu H Front Med (Lausanne). 2021; 8:665410.

PMID: 34113638 PMC: 8186265. DOI: 10.3389/fmed.2021.665410.

COVID-19's toll on the elderly and those with diabetes mellitus - Is vitamin B12 deficiency an accomplice?.

Wee A Med Hypotheses. 2020; 146:110374.

PMID: 33257090 PMC: 7659645. DOI: 10.1016/j.mehy.2020.110374.

New opportunities for designing effective small interfering RNAs.

Valdes J, Miller A Sci Rep. 2019; 9(1):16146.

PMID: 31695077 PMC: 6834666. DOI: 10.1038/s41598-019-52303-5.

References

Rijnbrand R, Abbink T, Haasnoot P, Spaan W, Bredenbeek P . The influence of AUG codons in the hepatitis C virus 5' nontranslated region on translation and mapping of the translation initiation window. Virology. 1996; 226(1):47-56. DOI: 10.1006/viro.1996.0626. View

Honda M, Brown E, Lemon S . Stability of a stem-loop involving the initiator AUG controls the efficiency of internal initiation of translation on hepatitis C virus RNA. RNA. 1996; 2(10):955-68. PMC: 1369429. View

Buratti E, Gerotto M, Pontisso P, Alberti A, Tisminetzky S, Baralle F . In vivo translational efficiency of different hepatitis C virus 5'-UTRs. FEBS Lett. 1997; 411(2-3):275-80. DOI: 10.1016/s0014-5793(97)00715-1. View

McLean G, Pathare P, Wilbur D, Morgan A, Woodhouse C, Schrader J . Cobalamin analogues modulate the growth of leukemia cells in vitro. Cancer Res. 1997; 57(18):4015-22. View

Pestova T, Shatsky I, Fletcher S, Jackson R, Hellen C . A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initiation of hepatitis C and classical swine fever virus RNAs. Genes Dev. 1998; 12(1):67-83. PMC: 316404. DOI: 10.1101/gad.12.1.67. View

Sizova D, Kolupaeva V, Pestova T, Shatsky I, Hellen C . Specific interaction of eukaryotic translation initiation factor 3 with the 5' nontranslated regions of hepatitis C virus and classical swine fever virus RNAs. J Virol. 1998; 72(6):4775-82. PMC: 110013. DOI: 10.1128/JVI.72.6.4775-4782.1998. View

McLean G, WILLIAMS M, Woodhouse C, Ziltener H . Transcobalamin II and in vitro proliferation of leukemic cells. Leuk Lymphoma. 1998; 30(1-2):101-9. DOI: 10.3109/10428199809050933. View

Gamarnik A, Andino R . Switch from translation to RNA replication in a positive-stranded RNA virus. Genes Dev. 1998; 12(15):2293-304. PMC: 317040. DOI: 10.1101/gad.12.15.2293. View

Neumann A, Lam N, Dahari H, Gretch D, Wiley T, Layden T . Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998; 282(5386):103-7. DOI: 10.1126/science.282.5386.103. View

10.

Hwang L, Hsieh C, Yen A, Chung Y, Chen D . Involvement of the 5' proximal coding sequences of hepatitis C virus with internal initiation of viral translation. Biochem Biophys Res Commun. 1998; 252(2):455-60. DOI: 10.1006/bbrc.1998.9673. View

11.

Zhao W, Wimmer E, Lahser F . Poliovirus/Hepatitis C virus (internal ribosomal entry site-core) chimeric viruses: improved growth properties through modification of a proteolytic cleavage site and requirement for core RNA sequences but not for core-related polypeptides. J Virol. 1999; 73(2):1546-54. PMC: 103979. DOI: 10.1128/JVI.73.2.1546-1554.1999. View

12.

Fanning L, Kenny E, Sheehan M, Cannon B, Whelton M, OConnell J . Viral load and clinicopathological features of chronic hepatitis C (1b) in a homogeneous patient population. Hepatology. 1999; 29(3):904-7. DOI: 10.1002/hep.510290310. View

13.

Sussman D, Greensides D, Reilly K, Wilson C . Preliminary characterization of crystals of an in vitro evolved cyanocobalamin (vitamin B12) binding RNA. Acta Crystallogr D Biol Crystallogr. 1999; 55(Pt 1):326-8. DOI: 10.1107/S0907444998004922. View

14.

Puoti C, Stati T, Magrini A . Serum HCV RNA titer does not predict the severity of liver damage in HCV carriers with normal aminotransferase levels. Liver. 1999; 19(2):104-9. DOI: 10.1111/j.1478-3231.1999.tb00018.x. View

15.

Wang S, Guo L, Allen E, Miller W . A potential mechanism for selective control of cap-independent translation by a viral RNA sequence in cis and in trans. RNA. 1999; 5(6):728-38. PMC: 1369800. DOI: 10.1017/s1355838299981979. View

16.

Seetharam B . Receptor-mediated endocytosis of cobalamin (vitamin B12). Annu Rev Nutr. 1999; 19:173-95. DOI: 10.1146/annurev.nutr.19.1.173. View

17.

Fire A . RNA-triggered gene silencing. Trends Genet. 1999; 15(9):358-63. DOI: 10.1016/s0168-9525(99)01818-1. View

18.

Shimoike T, MIMORI S, Tani H, Matsuura Y, Miyamura T . Interaction of hepatitis C virus core protein with viral sense RNA and suppression of its translation. J Virol. 1999; 73(12):9718-25. PMC: 113018. DOI: 10.1128/JVI.73.12.9718-9725.1999. View

19.

Barton D, Morasco B, Flanegan J . Translating ribosomes inhibit poliovirus negative-strand RNA synthesis. J Virol. 1999; 73(12):10104-12. PMC: 113062. DOI: 10.1128/JVI.73.12.10104-10112.1999. View

20.

Rijnbrand R, Lemon S . Internal ribosome entry site-mediated translation in hepatitis C virus replication. Curr Top Microbiol Immunol. 1999; 242:85-116. DOI: 10.1007/978-3-642-59605-6_5. View