Mucosal Transmission of Cell-Associated and Cell-Free Feline Immunodeficiency Virus

Abstract

Mucosal infection by feline immunodeficiency virus (FIV) was assessed via a single exposure of the vaginal or rectal mucosa to either infectious peripheral blood mononuclear cells (PBMCs), infectious plasma, or cell-free cultured virus. All cats inoculated with cell-free cultured virus (100 or 400 TCID) and 9 of 10 cats inoculated with infected PBMCs (2 x 10(7) or 2 x 10(5)) became persistently viremic within 3 weeks. Neither cat inoculated with 2 x 10(3) PBMCs became viremic. Rectal and vaginal exposure were equally effective routes to induce viremia. CD4+ T cells and mitogen-stimulated PBMC proliferation declined in all infected cats. However, a transient PBMC proliferative response to FIV p24gag occurred in most virus-exposed cats, especially those that did not develop detectable infection. FIV was not transmitted by mucosal exposure to infectious virus in plasma (100 TCID), a dose > 10-fold that needed for infection by parental injection. In vitro studies suggested that a plasma heat-stable virus-neutralizing factor may be associated with failure of plasma virus to establish infection via the mucosal route. Mucosal FIV infection provides a new model with which to study early stages of infection and intervention in transmucosal lentivirus infections.

Lactobacilli-Expressed Single-Chain Variable Fragment (scFv) Specific for Intercellular Adhesion Molecule 1 (ICAM-1) Blocks Cell-Associated HIV-1 Transmission across a Cervical Epithelial Monolayer

“…At acidic pH cell migration is greatly reduced (39), which may account for the poor cell-associated transmission observed in the macaque studies. The mouse vagina maintains a neutral pH as does the feline vagina, which has been shown to support transmission of cell-associated feline immunodeficiency virus (7).…”

“…Animal models of related retroviral infections have been used to address the relative importance of cell-associated and cell-free HIV-1 transmission. Cellassociated virus is transmitted in the human PBL (HuPBL) 4 -SCID model of vaginal transmission (5), whereas both cell-free and cellassociated virus are infectious when administered vaginally in the HIV/chimpanzee (6) and feline immunodeficiency virus/cat models (7,8). In the SIV/macaque model, cell-free SIV was transmitted vaginally, whereas infected mononuclear cells were incapable of transmitting SIV (9).…”

Mucosal defence along the gastrointestinal tract of cats and dogs

“…More recent studies with feline immunodeficiency virus (FIV) serve to highlight the difficulties associated with generating protective mucosal responses. FIV is a natural pathogen of cats, which although it is considered to be normally transmitted by biting, can be experimentally infected by both rectal and vaginal routes [5,11]. Experimental studies have demonstrated that vaccination regimes that provide protection from intraperitoneal challenge fail to protect from rectal or vaginal challenge [19].…”

Oral Immunization with RecombinantListeria monocytogenesControls Virus Load after Vaginal Challenge with Feline Immunodeficiency Virus

“…The feline model of infection and disease progression is uniquely relevant for the evaluation of vaccine design and immune response upon challenge (22,34,61). Cats are the natural hosts for FIV and can be infected by the vaginal route with either cell-free or cell-associated virus, thereby mimicking the natural route of infection by HIV (11). We show here that a single oral immunization with a novel recombinant L. monocytogenes strain conferred some control of viral load after vaginal challenge with FIV.…”