Endogenization of a Prosimian Retrovirus during Lemur Evolution.

Studies of viruses that coevolved with lemurs provide an opportunity to understand the basal traits of primate viruses and provide an evolutionary context for host-virus interactions. Germline integration of endogenous retroviruses (ERVs) are fossil evidence of past infections. Hence, characterization of novel ERVs provides insight into the ancient precursors of extant viruses and the evolutionary history of their hosts. Here, we report the discovery of a novel endogenous retrovirus present in the genome of a lemur, Coquerel's sifaka (Propithecus coquereli). Using next-generation sequencing, we identified and characterized the complete genome sequence of a retrovirus, named prosimian retrovirus 1 (PSRV1). Phylogenetic analyses indicate that PSRV1 is a gamma-type betaretrovirus basal to the other primate betaretroviruses and most closely related to simian retroviruses. Molecular clock analysis of PSRV1 long terminal repeat (LTR) sequences estimated the time of endogenization within 4.56 MYA (± 2.4 MYA), placing it after the divergence of Propithecus species. These results indicate that PSRV1 is an important milestone of lemur evolution during the radiation of the Propithecus genus. These findings may have implications for both human and animal health in that the acquisition of a gamma-type env gene within an endogenized betaretrovirus could facilitate a cross-species jump between vertebrate class hosts.

Adenoviruses of the most ancient primate lineages support the theory on virus-host co-evolution.

The scarcity or complete lack of information on the adenoviruses (AdVs) occurring in the most ancient non-human primates resulted in the initiation of a study for exploring their abundance and diversity in prosimians and New World monkeys (NWMs). In order to assess the variability of these AdVs and the possible signs of the hypothesised virus-host co-evolution, samples from almost every family of NWMs and prosimians were screened for the presence of AdVs. A PCRscreening of 171 faecal or organ samples from live or dead, captive or wild-living prosimians and NWMs was performed. The PCR products from the gene of the IVa2 protein were sequenced and used in phylogeny calculations. The presence of 10 and 15 new AdVs in seven and ten different species of prosimians and NWMs was revealed, respectively. Phylogenetic analysis indicated that the tentative novel AdVs cluster into two separate groups, which form the most basal branches among the primate AdVs, and therefore support the theory on the co-evolution of primate AdVs with their hosts. This is the first report that provides a comprehensive overview of the AdVs occurring in prosimians and NWMs, and the first insight into the evolutionary relationships among AdVs from all major primate groups.

An endogenous foamy virus in the aye-aye (Daubentonia madagascariensis).

We report the discovery and analysis of an endogenous foamy virus (PSFVaye) within the genome of the aye-aye (Daubentonia madagascariensis), a strepsirrhine primate from Madagascar. Phylogenetic analyses indicate that PSFVaye is divergent from all known simian foamy viruses, suggesting an association between foamy viruses and primates since the haplorrhine-strepsirrhine split. The discovery of PSFVaye indicates that primate foamy virus might be more broadly distributed than previously thought.

Simian T-lymphotropic virus diversity among nonhuman primates, Cameroon.

Cross-species transmission of retroviruses is common in Cameroon. To determine risk for simian T-cell lymphotropic virus (STLV) transmission from nonhuman primates to hunters, we examined 170 hunter-collected dried blood spots (DBS) from 12 species for STLV. PCR with generic tax and group-specific long terminal repeat primers showed that 12 (7%) specimens from 4 nonhuman primate species were infected with STLV. Phylogenetic analyses showed broad diversity of STLV, including novel STLV-1 and STLV-3 sequences and a highly divergent STLV-3 subtype found in Cercopithecus mona and C. nictitans monkeys. Screening of peripheral blood mononuclear cell DNA from 63 HTLV-seroreactive, PCR-negative hunters did not identify human infections with this divergent STLV-3. Therefore, hunter-collected DBS can effectively capture STLV diversity at the point where pathogen spillover occurs. Broad screening using this relatively easy collection strategy has potential for large-scale monitoring of retrovirus cross-species transmission among highly exposed human populations.

Structure and function of CC-chemokine receptor 5 homologues derived from representative primate species and subspecies of the taxonomic suborders Prosimii and Anthropoidea.

A chemokine receptor from the seven-transmembrane-domain G-protein-coupled receptor superfamily is an essential coreceptor for the cellular entry of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) strains. To investigate nonhuman primate CC-chemokine receptor 5 (CCR5) homologue structure and function, we amplified CCR5 DNA sequences from peripheral blood cells obtained from 24 representative species and subspecies of the primate suborders Prosimii (family Lemuridae) and Anthropoidea (families Cebidae, Callitrichidae, Cercopithecidae, Hylobatidae, and Pongidae) by PCR with primers flanking the coding region of the gene. Full-length CCR5 was inserted into pCDNA3.1, and multiple clones were sequenced to permit discrimination of both alleles. Compared to the human CCR5 sequence, the CCR5 sequences of the Lemuridae, Cebidae, and Cercopithecidae shared 87, 91 to 92, and 96 to 99% amino acid sequence homology, respectively. Amino acid substitutions tended to cluster in the amino and carboxy termini, the first transmembrane domain, and the second extracellular loop, with a pattern of species-specific changes that characterized CCR5 homologues from primates within a given family. At variance with humans, all primate species examined from the suborder Anthropoidea had amino acid substitutions at positions 13 (N to D) and 129 (V to I); the former change is critical for CD4-independent binding of SIV to CCR5. Within the Cebidae, Cercopithecidae, and Pongidae (including humans), CCR5 nucleotide similarities were 95.2 to 97.4, 98.0 to 99.5, and 98.3 to 99.3%, respectively. Despite this low genetic diversity, the phylogeny of the selected primate CCR5 homologue sequences agrees with present primate systematics, apart from some intermingling of species of the Cebidae and Cercopithecidae. Constructed HOS.CD4 cell lines expressing the entire CCR5 homologue protein from each of the Anthropoidea species and subspecies were tested for their ability to support HIV-1 and SIV entry and membrane fusion. Other than that of Cercopithecus pygerythrus, all CCR5 homologues tested were able to support both SIV and HIV-1 entry. Our results suggest that the shared structure and function of primate CCR5 homologue proteins would not impede the movement of primate immunodeficiency viruses between species.

Borna disease virus.

Borna disease virus (BDV) is unique amongst animal RNA viruses in its molecular biology and capacity to cause persistent, noncytolytic CNS-infection in a wide variety of host species. Unlike other non-segmented negative-strand RNA animal viruses, BDV replicates in the nucleus of the host cell where splicing is employed for expression of a very compact genome. Epidemiological studies indicate a broad host range and geographical distribution, and some investigators have proposed that human infection may result in neuropsychiatric disorders. Experimental Borna disease in neonatal and adult rats provides an intriguing model for immune-mediated disturbances of brain development and function.

TT virus infection in nonhuman primates and characterization of the viral genome: identification of simian TT virus isolates.

Newly discovered TT virus (TTV) is widely distributed in human populations. To understand more about the relationship between TTV and its hosts, we tested 400 sera from various nonhuman primates for the presence of TTV DNA by PCR assay. We collected serum samples from 24 different species of nonhuman primates. TTV DNA was determined by PCR with primers designed from the 5'-end region of the TTV genome. Nucleotide sequencing and phylogenetic analysis of viral genomes were also performed. TTV DNA was detected in 87 of 98 (89%) chimpanzees and 3 of 21 (14%) crab-eating macaques. Nucleotide sequences of the PCR products obtained from both animals were 80 to 100% identical between two species. In contrast, the sequences differed from TTV isolates in humans by 24 to 33% at the nucleotide level and 36 to 50% at the amino acid level. Phylogenetic analysis demonstrated that all TTV isolates obtained from simians were distinct from the human TTV isolates. Furthermore, TTV in simians, but not in humans, was classified into three different genotypes. Our results indicate that TTV in simians represents a group different from, but closely related to, TTV in humans. From these results, we tentatively named this TTV simian TTV (s-TTV). The existence of the s-TTV will be important in determining the origin, nature, and transmission of human TTV and may provide useful animal models for studies of the infection and pathogenesis of this new DNA virus.