Vitamin B12 and hepatitis C: molecular biology and human pathology.
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.
Lott
W B
WB
Clinical Medical Virology Research Centre, University of Queensland, St. Lucia, Queensland 4067, Australia. w.lott@mailbox.uq.edu.au
Takyar
S S
SS
Tuppen
J
J
Crawford
D H
DH
Harrison
M
M
Sloots
T P
TP
Gowans
E J
EJ
D000998:Antiviral Agents / Q000097:blood / Q000494:pharmacology; D001483:Base Sequence; D006692:Classical Swine Fever Virus / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004686:Encephalomyocarditis virus / Q000187:drug effects / Q000235:genetics; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006526:Hepatitis C / Q000097:blood / Q000821:virology*; D006801:Humans; D008099:Liver / Q000821:virology; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D014805:Vitamin B 12 / Q000097:blood / Q000494:pharmacology*
D000998:Antiviral Agents; D014805:Vitamin B 12