Lactoferrin and cyclic lactoferricin inhibit the entry of human cytomegalovirus into human fibroblasts.
Lactoferrin is mainly produced by polymorphonuclear leukocytes and has been demonstrated in mammalian milk and external secretions. Lactoferrin is an iron-binding, multifunctional protein and may play an important role in immune regulation and in defense mechanisms against bacteria, fungi and viruses. Lactoferricin is a potent antimicrobial peptide generated from the N-terminal part of lactoferrin by pepsin cleavage. We demonstrate that lactoferrins from different species and its N-terminal peptide lactoferricin (particularly the cyclic form) inhibit expression of early and late antigens, as well as production of infectious viral progeny during human cytomegalovirus (HCMV) infection in vitro. Iron-saturated lactoferrin did not affect HCMV antigen expression. Heparin had the same effects as iron-depleted lactoferrin. Yet, mixtures of lactoferrin and heparin did not inhibit HCMV multiplication i.e. lactoferrin and heparin seemed to mutually block each other's antiviral activities. HCMV-infected cells exposed to lactoferrin and cyclic lactoferricin contained less intracellular virus than unexposed cells. The antiviral activity of cyclic lactoferricin was more than seven-fold weaker than that of the maternal molecule. Lactoferrin and cyclic lactoferricin prevented HCMV entrance into the host cell.
Andersen
J H
JH
Department of Microbiology, University Hospital of Tromsø, N 9038 Tromsø, Norway. mlabjeh@rito.no
Osbakk
S A
SA
Vorland
L H
LH
Traavik
T
T
Gutteberg
T J
TJ
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects* / Q000254:growth & development; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D007781:Lactoferrin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*
D000998:Antiviral Agents; D010456:Peptides, Cyclic; C082171:lactoferricin B; D007781:Lactoferrin