FIV MODEL OF IN UTERO HIV INFECTION AND INTERVENTION

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The objective of this research is to investigate pathogenetic mechanisms of transplacental feline immunodeficiency virus (FIV) transmission as a guide towards better understanding antenatal mother-to-infant HIV-1 transmission. The 3 specific aims are: (1) to determine the precise gestational interval during which virus transmission occurs and to assess the role of maternal and viral factors related to risk of fetal infection, (2) to identify tissue tropisms and specific placental and fetal cells involved in virus dissemination, and (3) to compare strains of FIV which are and are not vertically transmitted in order to elucidate strain-specific factors responsible for cross-placental passage and fetal infectivity. In aim 1, the timing of transplacental FIV transmission will be determined by assessing infection prevalence rates for cesarean-collected fetuses at multiple gestational time points representing all pregnancy trimesters. Statistical correlations will be sought between maternal blood and immunologic parameters and circulating viral and tissue proviral loads as they affect risk of fetal infection. In aim 2, dissociated whole tissues will be assayed for FIV infection. For tissues identified as FIV-tropic, infectivity of specific cells will be determined by immunohistochemical strains and by primary cell culture. In aim 3, cats infected with FIV clade A and C isotypes will be assessed for their ability to transmit virus transplacentally. If virus is transmitted to fetuses, tissue and cell tropisms will be determined as for the prototype FIV-B-2542 strain used in aim 1 which is known to infect about 50% of fetuses. The above studies will provide information pertinent to understanding the pathogenesis and intervention of transplacental HIV-1 transmission.