MATERNAL-FETAL INTERACTIONS AFFECT GROWTH OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TRANSGENIC MICE

Infants vertically infected with human immunodeficiency virus type 1 ( HIV-1) often manifest profoundly deficient growth with failure to thri ve. The pathologic mechanisms that produce growth failure associated w ith pediatric HIV infection are not clear. Transgenic mice homozygous for a gag/pol deletion mu tant of the infectious provirus pNL4-3 have been found to manifest a similar growth failure pattern. To explore th e influence of HIV-1 on fetal growth and maternal-fetal interactions, we examined intrauterine growth of transgenic and nontransgenic mice a nd evaluated the consequence of embryo transfer into normal and hetero zygous transgenic mothers. Mice homozygous for the HIV transgene had n ormal intrauterine and birth weights but uniformly displayed severe gr owth retardation postnatally. Transgene expression was prominent in tr ansgenic fetuses and their placentas and in uteri of transgenic mother s, as determined by Northern analysis. Although embryo transfer did no t affect intrauterine growth, the pregnancy rate in transgenic mothers was markedly lower than in nontransgenic controls. In both fetal and neonatal tissues, transgene expression was significantly greater in ho mozygous animals when compared with heterozygotes, but the difference was magnified postnatally. These results suggest that HIV gene express ion affected both mother and neonate. In the mother, expression of the HIV-1 transgene reduced postfertilization pregnancy rate, Once the an imal was pregnant, however, the effects of transgene expression on the homozygous fetus were overcome in utero, possibly by the contribution of maternal factors or by inhibition of HIV-1 gene expression by a fe tal or maternal factor(s). In the neonate, HIV-1 transgene expression increased dramatically in homozygotes and was associated with profound growth failure. Thus, the expression of HIV-1 and its consequences ar e complex and dependent on important maternal-fetal interactions.