The investigators propose to use feline immunodeficiency virus (FIV) mother-to-offspring transmission to investigate aspects of HIV perinatal transmission and intervention that are difficult to study in patients. Two pathways of perinatal transmission will be modeled: 1) in utero, and 2) intrapartum/neonatal mucosal.
Four specific aims will be addressed.
Aim 1 will use pregnant cats chronically infected with FIV isolate FIV- B-2542, known to be transmitted vertically to >50% of offspring by both prenatal and postnatal pathways. Virus burden will be monitored by QC- PCR and dilutional coculture. Fetuses and placentas will be surgically removed at sequential stages of gestation and assayed for virus and target cells.
Aim 2 will assess the capacity of two antiviral drugs shown to be active in vivo against FIV infection to lower maternal virus load and prevent or significantly decrease in utero transmission when administered to the mother and neonate.
Aim 3 will focus on the earliest phase of neonatal mucosal infection in neonatal kittens receiving a single oral/nasal exposure to FIV using serial in situ hybridization and cell phenotyping to establish portal(s) of entry, cell and tissue replication stages and kinetics of virus spread to local cell populations.
In Aim 4, the model will be used to assess the ability of antiretroviral drugs to interrupt intrapartum/perinatal infection. Therapy will be initiated immediately (<1 hour) after exposure and if successful, subsequent studies will explore the duration of treatment and maximal interval between mucosal exposure and treatment to achieve a successful therapeutic outcome. The results of these studies should contribute information pertinent to early events in lentivirus transmission and intervention strategies to combat mother-to-infant transmission.
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| Allison, Robin W; Hoover, Edward A (2003) Covert vertical transmission of feline immunodeficiency virus. AIDS Res Hum Retroviruses 19:421-34 |
| Obert, Leslie A; Hoover, Edward A (2002) Early pathogenesis of transmucosal feline immunodeficiency virus infection. J Virol 76:6311-22 |
| Rogers, Arlin B; Hoover, Edward A (2002) Fetal feline immunodeficiency virus is prevalent and occult. J Infect Dis 186:895-904 |
| Rogers, Arlin B; Mathiason, Candace K; Hoover, Edward A (2002) Immunohistochemical localization of feline immunodeficiency virus using native species antibodies. Am J Pathol 161:1143-51 |
| Rogers, A B; Hoover, E A (1998) Maternal-fetal feline immunodeficiency virus transmission: timing and tissue tropisms. J Infect Dis 178:960-7 |
| O'Neil, L L; Burkhard, M J; Obert, L A et al. (1997) Regression of feline immunodeficiency virus infection. AIDS Res Hum Retroviruses 13:713-8 |
