Effect of maternal treatment with cyclic HPMPC in the guinea pig model of congenital cytomegalovirus infection.
BACKGROUND
Cytomegalovirus (CMV) infection of the fetus is the leading cause of congenital infection. Using the guinea pig model of congenital CMV infection, we sought to determine whether antiviral treatment of a CMV-infected dam could improve the outcome of offspring.


METHODS
Pregnant Hartley guinea pigs were inoculated with guinea pig CMV (GPCMV) during the late second/early third trimester of gestation. Guinea pigs received either 1 dose of cyclic 1-[((s)-2-hydroxy-2-oxo-1,4,2,-dioxaphosphorinan-5-yl)methyl]cytosine dihydrate (cHPMPC; 35 mg/kg) or placebo 24 h after GPCMV infection. Guinea pigs were monitored until delivery or were killed 10 days after infection, for the evaluation of the effect of cHPMPC on viral replication by polymerase chain reaction analysis in various dam and pup tissues.


RESULTS
cHPMPC treatment of infected dams improved pup survival from 28.2% (11/39) to 83.7% (36/43) (P < .001) and extended the duration of pregnancy. cHPMPC treatment did not prevent infection of the placenta or disseminated infection of the dam and pup but significantly decreased the amount of GPCMV in tissues. GPCMV DNA levels in the placenta were reduced from 3.54 to 2.12 log(10) genome copies/ mu g of DNA (P < .0001).


CONCLUSIONS
Treatment of the GPCMV-infected pregnant dam with 1 dose of cHPMPC improves the outcome of congenital infection and decreases viral replication in a guinea pig model.
Bravo
Fernando J
FJ
Cincinnati Children's Hospital Medical Center, OH 45229, USA.
Cardin
Rhonda D
RD
Bernstein
David I
DI
D000818:Animals; D000831:Animals, Newborn / Q000382:microbiology; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control / Q000635:transmission / Q000662:veterinary; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D007112:Immunity, Maternally-Acquired; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D011247:Pregnancy; D011256:Pregnancy Outcome; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D009943:Organophosphorus Compounds; C072572:cyclic-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine; D003596:Cytosine