Neurologic Disease in Captive Lions (Panthera leo) with Low-Titer Lion Lentivirus Infection

Abstract

Lion lentivirus (LLV; also known as feline immunodeficiency virus of lion, Panthera leo [FIVPle]) is present in free-ranging and captive lion populations at a seroprevalence of up to 100%; however, clinical signs are rarely reported. LLV displays up to 25% interclade sequence diversity, suggesting that it has been in the lion population for some time and may be significantly host adapted. Three captive lions diagnosed with LLV infection displayed lymphocyte subset alterations and progressive behavioral, locomotor, and neuroanatomic abnormalities. No evidence of infection with other potential neuropathogens was found. Antemortem electrodiagnostics and radiologic imaging indicated a diagnosis consistent with lentiviral neuropathy. PCR was used to determine a partial lentiviral genomic sequence and to quantify the proviral burden in eight postmortem tissue specimens. Phylogenetic analysis demonstrated that the virus was consistent with the LLV detected in other captive and free-ranging lions. Despite progressive neurologic signs, the proviral load in tissues, including several regions of the brain, was low; furthermore, gross and histopathologic changes in the brain were minimal. These findings suggest that the symptoms in these animals resulted from nonspecific encephalopathy, similar to human immunodeficiency virus, FIV, and simian immunodeficiency virus (SIV) neuropathies, rather than a direct effect of active viral replication. The association of neuropathy and lymphocyte subset alterations with chronic LLV infection suggests that long-term LLV infection can have detrimental effects for the host, including death. This is similar to reports of aged sootey mangabeys dying from diseases typically associated with end-stage SIV infection and indicates areas for further research of lentiviral infections of seemingly adapted natural hosts, including mechanisms of host control and viral adaptation.Lion lentivirus (LLV; also known as feline immunodeficiency virus [FIV] of lion, Panthera leo [FIVPle]) is an FIV that is related to yet distinct from the domestic cat (Felis catus) FIV (4, 52). LLV is present in free-ranging prides at seroprevalence rates that approach 100% and is commonly detected in captive lion (Panthera leo) populations, suggesting that it is efficiently transmitted (4,19,22,25,32,42,50,52,53). Five distinct heterogeneous clades of LLV have been identified on the basis of sequence analysis of a conserved region of the pol gene. Up to 25% sequence diversity between clades has been noted in this highly conserved region of the lentiviral genome, suggesting that, for such genetic heterogeneity to occur, this virus has infected the lion population for a considerable time (4,52,53). LLV apparently causes little or no clinical disease in free-ranging lions, although clinical signs and immunopathology reminiscent of lentiviral infection have been reported in geriatric captive animals, perhaps due to their longer life spans and/or stress-related cofactors in these cohorts (6,19,22,41,42).The effects of FIV on do...

Going Wild: Lessons from Naturally Occurring T-Lymphotropic Lentiviruses

“…While it appears that the trend is for naturally occurring infections to be apathogenic for native hosts, several reports implicating both FIV and SIV diseases have been published, typically from captive settings where animals have outlived their "normal" life span. For example, an aged FIVplepositive captive lion developed lymphoma (312), and three aged FIVple-infected lions in the Columbus zoo developed neurological disease reminiscent of HIV-induced encephalitis (51). There is also a trend for FIV-infected lions and pumas to experience CD4 ϩ T-cell depletion, similar to that noted in domestic cats infected with virulent FIV (55,319).…”

“…The most comprehensive of these (43) demonstrated a range of 30 to 6.7 ϫ 10 4 copies of provirus/10 6 PBMC, similar to the proviral burden detected in peripheral lymph nodes (LNs). The proviral load in this cohort was correlated with both the (51).…”

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

“…Previous studies support this conclusion, as even species-specific (nondegenerate) primers can have low sensitivity (Brown et al, 1994;Carpenter et al, 1996;Troyer et al, 2005). Deoxyribonucleic acid PCR may have low sensitivity for detecting lentiviral strains because of low proviral load in blood cells (Blake et al, 2006;Brennan et al, 2006). Further, although use of degenerate primers enhances the ability to detect uncharacterized viral isolates, it simultaneously limits efficiency of PCR reactions by limiting the amount of primer in the reaction that complements the DNA sample.…”

FIV diversity: FIVPle subtype composition may influence disease outcome in African lions

“…Long term surveillance of non-domestic felids infected with FIV, as well as evidence from free-ranging populations of pumas ( Puma concolor ) and lions ( Panthera leo ), suggest that these viruses are ancient, host-adapted, and have little to no negative impact on life-history parameters such as longevity (Biek et al, 2006; Carpenter and O'Brien, 1995; Packer et al, 1999). However, a few clinical studies have revealed that individuals of these same species may demonstrate FIV-associated immune depletion and, in some cases, AIDS-like complications and death (Brennan et al, 2006; Brown et al, 2010; Bull et al, 2002; Bull et al, 2003; Roelke et al, 2009; Roelke et al, 2006). Data on life history and clinical parameters are rare, and seldom collected in the same population.…”