Oral/nasal exposure of neonatal kittens to feline immunodeficiency virus (FIV) will be used to model the intrapartum/neonatal pathway of HIV vertical transmission and thereby investigate aspects of HIV perinatal transmission and intervention that are difficult to study in patients.
Two specific aims will be addressed: (1) the sequence and identity of the earliest target cells during intrapartum/neonatal mucosal infection and (2) the efficacy of perinatal therapeutic intervention for intrapartum/neonatal mucosal FIV infection.
Aim 1 will focus on the earliest phases of perinatal mucosal lentivirus infection in neonatal kittens receiving a single oral/nasal exposure to FIV. During the first 10 days of infection groups of infected kittens and a control animal will be serially sacrificed so that relevant mucosal and lymphoid tissue sites can be examined using in situ hybridization to detect FIV virus-replicating (viral mRNA) cells. Concurrent immunohistochemistry and histopathology will be performed to reveal the phenotype of the early target cells. The model developed in Aim 1 will be utilized in Aim 2 to assess the ability of antiretroviral drug therapy to interrupt intrapartum/neonatal FIV/HIV infection. Initiation of therapy immediately (<1 hour) after exposure will be studied first. If successful, subsequent studies will explore the maximum interval between mucosal virus exposure and treatment initiation to achieve a successful therapeutic outcome. The results of these studies should contribute information pertinent to early events in lentivirus transmission and to intervention strategies to combat mother-to-infant HIV transmission. Dr. Obert will devote 95-100 percent time to this project.
| Obert, Leslie A; Hoover, Edward A (2002) Early pathogenesis of transmucosal feline immunodeficiency virus infection. J Virol 76:6311-22 |
