Puma Lentivirus Is Controlled in Domestic Cats after Mucosal Exposure in the Absence of Conventional Indicators of Immunity

Abstract

A high percentage of free-ranging pumas (Felis concolor) are infected with feline lentiviruses (puma lentivirus, feline immunodeficiency virus Pco [FIV-Pco], referred to here as PLV) without evidence of disease. PLV establishes productive infection in domestic cats following parenteral exposure but, in contrast to domestic cat FIV, it does not cause T-cell dysregulation. Here we report that cats exposed to PLV oro-nasally became infected yet rapidly cleared peripheral blood mononuclear cell (PBMC) proviral load in the absence of a correlative specific immune response. Two groups of four specific-pathogen-free cats were exposed to PLV via the mucosal (oro-nasal) or parenteral (i.v.) route. All animals were PBMC culture positive and PCR positive within 3 weeks postinfection and seroconverted without exhibiting clinical disease; however, three or four oro-nasally infected animals cleared circulating proviral DNA within 3 months. Antibody titers reached higher levels in animals that remained persistently infected. PLV antigen-induced proliferation was slightly greater in mucosally inoculated animals, but no differences were noted in cytotoxic T-lymphocyte responses or cytokine profiles between groups. The distribution of virus was predominantly gastrointestinal as opposed to lymphoid in all animals in which virus was detected at necropsy. Possible mechanisms for viral clearance include differences in viral fitness required for crossing mucosal surfaces, a threshold dose requirement for persistence, or an undetected sterilizing host immune response. This is the first report of control of a productive feline or primate lentivirus infection in postnatally exposed, seropositive animals. Mechanisms underlying this observation will provide clues to containment of immunodeficiency disease and could prompt reexamination of vaccine-induced immunity against human immunodeficiency virus and other lentiviruses.

Variability in assays used for detection of lentiviral infection in bobcats (Lynx rufus), pumas (Puma concolor), and ocelots (Leopardus pardalis)

“…Barr, et al (1989) considered a single band on immunoblot to be equivocal with a high probability that the sample was positive. The four aforementioned experimental studies in domestic cats (VandeWoude et al, 1997a(VandeWoude et al, , 2003Sondgeroth et al, 2005;TerWee et al, 2005) had 100% specificity using one band as a positive indicator. Further, the sensitivity was high because 25 of 27 domestic cats that were inoculated with PLV were positive by PLV immunoblot, viral coculture, and PCR.…”

“…All positive samples, including positive controls, had similar banding patterns characterized by greater affinity for the p24 antigen than any other antigen, suggesting that all positive results were true positives and not unspecific antibody binding. Further, during experimental infection of domestic cats with PLV, PLV immunoblots were 100% specific for PLV infection because none of the 19 sham-inoculated animals used in controlled studies were positive by PLV immunoblot, coculture, or PCR (VandeWoude et al, 1997a;VandeWoude et al, 2003;Sondgeroth et al, 2005;TerWee et al, 2005).…”

“…Antigens were prepared from viral cultures of domestic cat FIV (FIV-B2546), puma lentivirus (PLV-1695), and lion lentivirus (LLV-438). Stocks were grown in domestic cat origin cell line Mya-1 (Miyazawa et al, 1989), and viral proteins were isolated as previously described (VandeWoude et al, 1997b;TerWee et al, 2005). Reverse-transcriptase positive tissue culture supernatant was centrifuged at 200 3 G (GPR centrifuge, Beckman Instruments, Inc., Fullerton, California, USA) for 10 min at 5 C to remove cellular material.…”

The molecular biology and evolution of feline immunodeficiency viruses of cougars

“…Cats can be persistently infected with PLV by either the oral nasal (ON) or intravenously (IV) routes but there are no clinical consequences of the infection (VandeWoude et al, 1997;Terwee et al, 2005). Despite the fact that in the majority of ON-inoculated cats the virus levels dropped below the level of detection at time points when viremia was still apparent in IV-inoculated cats, there were no differences in immunological profiles of cats.…”

Detection and Genetic Analysis of Feline Immunodeficiency Virus (FIVple) in Southern African Lions (Panthera leo)

“…Lentiviral infections have also been detected in several nondomestic feline species, including in African lion (FIVple) populations in eastern and southern Africa (Panthera leo), but significant sequence divergence exists among the feline lentiviruses of different host species, with as much as 30% diversity in the conserved regions of the polymerase gene (Pol), and even higher diversity in the regions encoding the envelope glycoprotein and core protein (Brown et al 1994;Langley et al 1994;Carpenter et al 1998;Terwee et al 2005;Troyer et al 2005). Diversity is also pronounced among the feline lentiviruses infecting a single nondomestic host species, where as much as a 20% divergence may exist in the Pol region among different isolates (Brown et al 1994;Carpenter et al 1998;Terwee et al 2005;Troyer et al 2005). These findings are in contrast to FIVfca, where viral subtypes, or clades, differ in their nucleotide sequences by only 5-10% across the entire genome (Sodora et al 1995;Carpenter et al 1998).…”