Restrictions to cross-species transmission of lentiviral infection gleaned from studies of FIV

Abstract

More than 40 species of primates and over 20 species of cats harbor antibodies that sero-react to lentiviral antigens. In nearly all cases where viral genetic analysis has been conducted, each host species is infected with a unique lentivirus. Though lentivirus clades within a species can be substantially divergent, they are typically monophyletic within that species. A notable significant departure from this observation is apparent cross-species transmission of FIV between bobcats (Lynx rufus) and pumas (Puma concolor) in Southern California that has occurred at least three times; evidence from one bobcat sequence suggests this cross-over may have also occurred in Florida between bobcats and the endangered Florida panther. Several other isolated reports demonstrate cross-species transmission of FIV isolates among captive animals housed in close proximity, and it is well established that HIV-1 and HIV-2 arose from human contact with SIV-infected non-human primates. Using an experimental model, we have determined that domestic cats (Felis catus) are susceptible to FIVs originating from pumas or lions. While infections are initially replicative, and animals seroconvert, within a relatively short period of time circulating virus is reduced to nearly undetectable levels in a majority of animals. This diminution of viral load is proportional to initial viral peak. Although viral reservoirs can be identified in gastrointestinal tissues, most viral genomes recovered peripherally are highly mutated, suggesting that the non-adapted host successfully inhibits normal viral replication, leading to replication incompetent viral progeny. Mechanisms possible for such restriction of cross-species infections in natural settings include: (1) Lack of contact conducive to lentiviral transmission between infected and shedding animals of different species; (2) Lack of suitable receptor repertoire to allow viral entry to susceptible cells of a new species; (3) Cellular machinery in the new host sufficiently divergent from the primary host to support viral replication (i.e. passive unfacilitated viral replication); (4) Intracellular restriction mechanisms present in the new host that is able to limit viral replication (i.e. active interrupted viral replication. These include factors that limit uncoating, replication, packaging, and virion release); (5) Unique ability of new host to raise sterilizing adaptive immunity, resulting in aborted infection and inability to spread infections among con-specifics; or (6) Production of defective or non-infectious viral progeny that lack cellular cofactors to render them infectious to con-specifics (i.e. particles lacking appropriate cellular components in viral Env to render them infectious to other animals of the same species). Data to support or refute the relative importance of each of these possibilities is described in this review. Insights based on our in vivo cross-species model suggest intracellular restriction mechanisms effectively inhibit rapid inter-specific transmission of lentiviruses. Further, limited contact both within and between species in natural populations is highly relevant to limiting the opportunity for spread of FIV strains. Studies of naturally occurring SIV and innate host restriction systems suggest these same two mechanisms are significant factors inhibiting widespread cross-species transmission of lentiviruses among primate species as well.

Figure 1

Unrooted maximum likelihood (ML) tree of a 500bp region in polRT demonstrating the relationship between FIV sequences from pumas and bobcats. Minimum evolution (ME), maximum parsimony (MP), and Bayesian analyses (random starting trees; burn-in values set at 45,000 generations; two simultaneous runs with four Markov chains each were run for one million generations and sampled every 20 generations) produced trees with similar topologies. Bootstrap values and posterior probabilities are included for nodes discussed in the text (ML/MP/ME/Bayesian). Colors represent the species of origin (blue=bobcat, red=puma). Viral sequences isolated from animals in California (CA) are highlighted and each sequence is identified by a location consisting of a country name or a state abbreviation followed by a specific site in parentheses for the CA samples (OC=Orange County, VC=Ventura County, SDRC=San Diego and Riverside Counties). Analyses used empirical base frequencies, an estimated shape parameter of 0.7495, and an estimated substitution matrix as follows: A/C = 2.8733, A/G = 12.0716, A/T = 0.8769, C/G = 4.8937, C/T = 16.8913, and an estimated proportion of invariant sites of 0.3419.