Format

Send to

Choose Destination
Antiviral Res. 2004 Sep;63(3):197-208.

Inhibition of cytomegalovirus infection by lactoferrin in vitro and in vivo.

Author information

1
Department of Pharmacokinetics and Drug Delivery, University Center for Pharmacy, Groningen University Institute for Drug Exploration (GUIDE), Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands, l.beljaars@farm.rug.nl

Abstract

Lactoferrin is an antimicrobial agent, that, amongst other viruses, inhibits cytomegalovirus (CMV). In this study, we addressed the mechanism(s) by which lactoferrin interacts with CMV and its target cells to inhibit infection. We also studied the antiviral activity of lactoferrin in vivo in rat CMV models with and without immune suppression. We cationized a protein of similar molecular weight, i.e. human serum albumin (HSA), as well as a protein with a smaller molecular weight (beta-lactoglobulin). While HSA itself displayed no anti-CMV activity in vitro, cationic HSA inhibited CMV replication to a similar extent as lactoferrin. Time-of-addition assays indicated that all cationic proteins interacted with an early event in the infection and pre-incubation of cells rather than of virus significantly reduced CMV replication. Rats were treated with lactoferrin (4, 40 or 160 mg/kg, intravenously), beginning at 6h after CMV administration. Subsequently, the rats were treated three times a week. As a positive control, CMV-infected rats were treated with cidofovir, and this agent proved to be highly active in the rat models for CMV. Treatment with lactoferrin was beneficial when infection was initiated with cell-free virus, but not with virus-infected leukocytes. Lactoferrin treatment led to a 10-fold reduction in the final virus titers (salivary glands) at 4 weeks after infection in the immunocompromised rats. Lactoferrin exerted its effects via inhibition of cell entry rather than via stimulation of the immune system.

PMID:
15451188
DOI:
10.1016/j.antiviral.2004.05.002
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center