Going wild: lessons from naturally occurring T-lymphotropic lentiviruses

Abstract

Over 40 nonhuman primate (NHP) species harbor species-specific simian immunodeficiency viruses (SIVs). Similarly, more than 20 species of nondomestic felids and African hyenids demonstrate seroreactivity against feline immunodeficiency virus (FIV) antigens. While it has been challenging to study the biological implications of nonfatal infections in natural populations, epidemiologic and clinical studies performed thus far have only rarely detected increased morbidity or impaired fecundity/survival of naturally infected SIV- or FIV-seropositive versus -seronegative animals. Cross-species transmissions of these agents are rare in nature but have been used to develop experimental systems to evaluate mechanisms of pathogenicity and to develop animal models of HIV/AIDS. Given that felids and primates are substantially evolutionarily removed yet demonstrate the same pattern of apparently nonpathogenic lentiviral infections, comparison of the biological behaviors of these viruses can yield important implications for host-lentiviral adaptation which are relevant to human HIV/AIDS infection. This review therefore evaluates similarities in epidemiology, lentiviral genotyping, pathogenicity, host immune responses, and cross-species transmission of FIVs and factors associated with the establishment of lentiviral infections in new species. This comparison of consistent patterns in lentivirus biology will expose new directions for scientific inquiry for understanding the basis for virulence versus avirulence.

FIG. 1.

Genomic organization of SIV and FIV strains belonging to different lineages. The SIV classification demonstrated is based on genomic structure relationships, which are not superimposable on phylogenetic relationships. For references, see Table 1.

FIG. 2.

FIVs appear to cluster phylogeographically rather than ancestrally. FIV sequences were analyzed phylogenetically from eight feline species (376) representing five of eight feline lineages (195). Comparison of FIV relationships with ancestral lineages does not demonstrate consistent relationships, as represented by lines drawn between FIVs and their corresponding familial groups. However, FIVs are roughly divided between New and Old World species, with relatively high bootstrap associations, suggesting that recent geography is more highly related to FIV strain relationships than are lineage radiations.

FIG. 3.

Comparison between SIV phylogeny (a) and primate phylogeny (b). (a) Neighbor-joining tree constructed from available SIV sequences; (b) primate phylogeny is shown by a schematic using relationships cited in the text. While general alignment of hosts and viruses can be observed, cross-species transmissions and viral recombination events make this correlation less than absolute. Asterisks indicate significant bootstrap values.

FIG. 4.

FIV neutralizing antibodies are FIV strain specific. Serially diluted sera from domestic cats (cat 1, naïve; cat 2, FIVfca infected, cat 3, FIVfca infected; cat 4, FIVpco infected), pumas (pumas 1 and 2, FIVpco infected), and lions (lion 1, FIVple clade A infected; lion 2, FIVple clade C infected) were tested for the ability to neutralize FIVfca (FIV-C clone) (97), FIVpco (PLV-1695) (367), and FIVple (LLV458) (376). The highest dilutions of sera that neutralized viral growth are indicated. Sera neutralized virus strain-matched FIVs most demonstrably.