Simian Foamy Viruses in Central and South America: A New World of Discovery.

Foamy viruses (FVs) are the only exogenous retrovirus to date known to infect neotropical primates (NPs). In the last decade, an increasing number of strains have been completely or partially sequenced, and molecular evolution analyses have identified an ancient co-speciation with their hosts. In this review, the improvement of diagnostic techniques that allowed the determination of a more accurate prevalence of simian FVs (SFVs) in captive and free-living NPs is discussed. Determination of DNA viral load in American primates indicates that oral tissues are the viral replicative site and that buccal swab collection can be an alternative to diagnose SFV infection in NPs. Finally, the transmission potential of NP SFVs to primate workers in zoos and primate centers of the Americas is examined.

Wide distribution and ancient evolutionary history of simian foamy viruses in New World primates.

BACKGROUND: Although simian foamy viruses (SFV) are the only exogenous retroviruses to infect New World monkeys (NWMs), little is known about their evolutionary history and epidemiology. Previous reports show distinct SFVs among NWMs but were limited to small numbers of captive or wild monkeys from five (Cebus, Saimiri, Ateles, Alouatta, and Callithrix) of the 15 NWM genera. Other studies also used only PCR testing or serological assays with limited validation and may have missed infection in some species. We developed and validated new serological and PCR assays to determine the prevalence of SFV in blood specimens from a large number of captive NWMs in the US (n = 274) and in captive and wild-caught NWMs (n = 236) in Peruvian zoos, rescue centers, and illegal trade markets. Phylogenetic and co-speciation reconciliation analyses of new SFV polymerase (pol) and host mitochondrial cytochrome B sequences, were performed to infer SFV and host co-evolutionary histories. RESULTS: 124/274 (45.2 %) of NWMs captive in the US and 59/157 (37.5 %) of captive and wild-caught NWMs in Peru were SFV WB-positive representing 11 different genera (Alouatta, Aotus, Ateles, Cacajao, Callithrix, Cebus, Lagothrix, Leontopithecus, Pithecia, Saguinus and Saimiri). Seroprevalences were lower at rescue centers (10/53, 18.9 %) compared to zoos (46/97, 47.4 %) and illegal trade markets (3/7, 8/19, 42.9 %) in Peru. Analyses showed that the trees of NWM hosts and SFVs have remarkably similar topologies at the level of species and sub-populations suggestive of co-speciation. Phylogenetic reconciliation confirmed 12 co-speciation events (p < 0.002) which was further supported by obtaining highly similar divergence dates for SFV and host genera and correlated SFV-host branch times. However, four ancient cross-genus transmission events were also inferred for Pitheciinae to Atelidae, Cacajao to ancestral Callithrix or Cebus monkeys, between Callithrix and Cebus monkeys, and Lagothrix to Alouatta. CONCLUSIONS: We demonstrate a broad distribution and stable co-speciation history of SFV in NWMs at the species level. Additional studies are necessary to further explore the epidemiology and natural history of SFV infection of NWMs and to determine the zoonotic potential for persons exposed to infected monkeys in captivity and in the wild.

Identification and characterization of highly divergent simian foamy viruses in a wide range of new world primates from Brazil.

Foamy viruses naturally infect a wide range of mammals, including Old World (OWP) and New World primates (NWP), which are collectively called simian foamy viruses (SFV). While NWP species in Central and South America are highly diverse, only SFV from captive marmoset, spider monkey, and squirrel monkey have been genetically characterized and the molecular epidemiology of SFV infection in NWPs remains unknown. We tested a large collection of genomic DNA (n = 332) comprising 14 genera of NWP species for the presence of SFV polymerase (pol) sequences using generic PCR primers. Further molecular characterization of positive samples was carried out by LTR-gag and larger pol sequence analysis. We identified novel SFVs infecting nine NWP genera. Prevalence rates varied between 14-30% in different species for which at least 10 specimens were tested. High SFV genetic diversity among NWP up to 50% in LTR-gag and 40% in pol was revealed by intragenus and intrafamilial comparisons. Two different SFV strains infecting two captive yellow-breasted capuchins did not group in species-specific lineages but rather clustered with SFVs from marmoset and spider monkeys, indicating independent cross-species transmission events. We describe the first SFV epidemiology study of NWP, and the first evidence of SFV infection in wild NWPs. We also document a wide distribution of distinct SFVs in 14 NWP genera, including two novel co-speciating SFVs in capuchins and howler monkeys, suggestive of an ancient evolutionary history in NWPs for at least 28 million years. A high SFV genetic diversity was seen among NWP, yet these viruses seem able to jump between NWP species and even genera. Our results raise concerns for the risk of zoonotic transmission of NWP SFV to humans as these primates are regularly hunted for food or kept as pets in forest regions of South America.

Novel polyomaviruses of nonhuman primates: genetic and serological predictors for the existence of multiple unknown polyomaviruses within the human population.

Polyomaviruses are a family of small non-enveloped DNA viruses that encode oncogenes and have been associated, to greater or lesser extent, with human disease and cancer. Currently, twelve polyomaviruses are known to circulate within the human population. To further examine the diversity of human polyomaviruses, we have utilized a combinatorial approach comprised of initial degenerate primer-based PCR identification and phylogenetic analysis of nonhuman primate (NHP) polyomavirus species, followed by polyomavirus-specific serological analysis of human sera. Using this approach we identified twenty novel NHP polyomaviruses: nine in great apes (six in chimpanzees, two in gorillas and one in orangutan), five in Old World monkeys and six in New World monkeys. Phylogenetic analysis indicated that only four of the nine chimpanzee polyomaviruses (six novel and three previously identified) had known close human counterparts. To determine whether the remaining chimpanzee polyomaviruses had potential human counterparts, the major viral capsid proteins (VP1) of four chimpanzee polyomaviruses were expressed in E. coli for use as antigens in enzyme-linked immunoassay (ELISA). Human serum/plasma samples from both Côte d'Ivoire and Germany showed frequent seropositivity for the four viruses. Antibody pre-adsorption-based ELISA excluded the possibility that reactivities resulted from binding to known human polyomaviruses. Together, these results support the existence of additional polyomaviruses circulating within the human population that are genetically and serologically related to existing chimpanzee polyomaviruses.

Comparative pathobiology of Kaposi sarcoma-associated herpesvirus and related primate rhadinoviruses.

With the emergence of the AIDS epidemic over the last 2 decades and the more recent identification of Kaposi sarcoma-associated herpesvirus (KSHV, Human herpesvirus 8), the genera of rhadinoviruses have gained importance as a family of viruses with oncogenic potential. First recognized in New World primates more than 30 y ago, the rhadinoviruses Saimiriine herpesvirus 2 and Ateline herpesvirus 2 have well-described transforming capabilities. Recently several new species-specific rhadinoviruses of Old World primates have been described, including retroperitoneal fibromatosis herpesvirus and rhesus rhadinovirus (Cercopithecine herpesvirus 17). Molecular analysis of these viruses has elucidated several functionally conserved genes and properties shared with KSHV involved in cellular proliferation, transformation, and immune evasion that facilitate the oncogenic potential of these viruses. This review examines the comparative pathobiology of KSHV, discusses the role of macaque rhadinoviruses as models of human disease, and outlines the derivation of specific pathogen-free animals.