In this project we will characterize Puerto Rican HIV-1 primary isolates from ten non-transmitter mothers and ten transmitter maternal-infant pairs to determine differences that are indicative of viral selection that could increase the risk of HIV vertical transmission. The hypothesis is that transmitter mother-infant pairs viral isolates will show a better replication kinetics or use other potential co-receptor beside CCR5 than non- transmitters. These characteristics may allow the virus the virus to be more efficient or aggressive, increasing the risk of HIV vertical transmission. HIV primary isolates replication kinetics will be assayed by measuring the HIVp24 antigen using three different types of cultures; 1) GHOST cell clines containing a specific co-receptor 2) PHA stimulated peripheral blood mononuclear cells and 3) Placental macrophages. Three hundred clones (ten clones of each patient) derived from HIV-1 primary isolates from ten non-transmitters and ten transmitters mothers-infant pairs for the V3 envelope gene will be obtained by the blunt end cloning technique, characterize to determine; 1) genetic differences or similarities between maternal-infant pairs and between transmitter and non- transmitter mothers, and 2) specific amino acid positions that could influence co-receptor utilization. An understanding of the mechanism and pathogenesis of perinatal transmission is crucial for the design of new preventive and therapeutic interventions since the development of vaccine could go a long way. These results will help us determine if other chemokine receptors play a role in maternal fetal transmission and if a better viral replication kinetics may increase the risk of transmission.
| Arroyo, M A; Tien, H; Pagan, M et al. (2002) Virologic risk factors for vertical transmission of HIV type 1 in Puerto Rico. AIDS Res Hum Retroviruses 18:447-60 |
