Mucosal transmission and early pathogenesis of feline immunodeficiency virus subtype C infection

Abstract

Human immunodeficiency virus infection is initiated by mucosal exposure; however, the early events resulting in mucosal infection are unknown and difficult to study in humans. Likewise, such issues are unresolved for mucosal feline immunodeficiency virus (FIV) infection and could be examined utilizing the FIV-feline model. I have focused on the mucosal transmissibility and early pathogenesis of infection by a subgroup C FIV (FTV-C), because this virus is unique in inducing high viral burdens and rapidly progressive infection in cats infected by serial intravenous passage. Neonatal and weanling cats were exposed to FTV-C via the oral, vaginal, or rectal routes. FIV-C proved to be transmissible by all three routes. Moreover, mucosal exposure of FTV-C resulted in a broader range of host-virus relationships than observed in the rapid parenteral serial passage studies. Similar to the latter studies, some of the vaginal inoculates developed a rapidly progressive course of FTV-C infection. However, rectal exposure was less efficient at inducing infection. A few animals developed regressive infections detectable rarely by virus isolation coculture (VI) or PCR and unaccompanied by hematologic abnormalities. The thymus was an early lymphoid system target organ in the FTV-C infections. The major thymic changes observed were depletion of dendritic, CD4+, and CD4+/CD8+ cells, and marked apoptosis. The magnitude of the thymic lesions correlated with disease severity. To identify the early target tissues in transmucosal lentivirus infection, cats infected oral-nasally or vaginally were necropsied at specific time points within the first twelve days post infection (PI). Mucosal tissues, regional lymph nodes (LNs), peripheral blood mononuclear cells (PBMC), and other tissues were collected and examined by VI, PCR, and in situ hybridization (ISH) to identify the earliest FIV target tissues. FTV provirus was detected rarely within regional LNs and PBMC before eight days PI by PCR. However, rare FIV-bearing cells were identified in regional LNs by two days PI by ISH. The earliest FIV-bearing cells demonstrated by ISH had morphologic characteristic of dendritic cells and macrophages and were located primarily in the follicular germinal centers and parafollicular areas of the LNs. Rare FTV+ cells also were identified within the epithelium and submucosa of mucosal tissues as early as one day PI.