Effect of desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) on rat cytomegalovirus replication in vitro and in vivo.
Cytomegalovirus (CMV) infection is a major problem in the immunosuppressed patient. It is thought that besides direct CMV induced cell lysis, immunological damage is part of CMV pathogenesis. New antiviral drugs, which combine immunomodulating and antiviral qualities, could be beneficial. Recently, it has been described that desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) exhibit both properties. In this report the antiviral effects of both compounds against rat CMV (RCMV) are described in vitro and in vivo using a generalised and local infection model. In vitro, both compounds exhibited a significant antiviral effect, DTPA being more potent than DFO. However, in the generalised infection model no effect was seen on mortality, morbidity or presence of virus in internal organs. In rats infected subcutaneously in the hind paw, no effect was seen locally on paw thickness, presence of viral antigens and inflammatory response. In addition, these rats suffered from a generalised infection of low magnitude at 15 days post infection, although both DFO and DTPA were able to lower the level of viral replication. In conclusion, our data indicate that despite in vitro activity, in vivo usage of DFO or DTPA for acute CMV infection is not warranted.
Kloover
J S
JS
Department of Medical Microbiology, University of Maastricht, The Netherlands.
Scholz
M
M
Cinatl
J
J
Lautenschlager
I
I
Grauls
G E
GE
Bruggeman
C A
CA
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003676:Deferoxamine / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008099:Liver / Q000821:virology; D004369:Pentetic Acid / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012469:Salivary Glands / Q000821:virology; D013154:Spleen / Q000821:virology; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*
D000956:Antigens, Viral; D000998:Antiviral Agents; D004369:Pentetic Acid; D003676:Deferoxamine