Identification of Simian Agent 10 as Human Parainfluenza Virus Type 3 Suggests Transmission of a Human Virus to an African Monkey

Abstract

The use of nonhuman primates in biomedical research has led to the isolation of many simian viruses (4, 5). These viruses were given either consecutive SV (simian virus; for isolates from Asian monkeys) or SA (simian agent; for isolates from African monkeys) numbers (7, 10). SA10 was first isolated from the mouth of a samango monkey (Cercopithecus mitis) in 1963 (10). Based on serological findings (10), SA10 has long been classified as a distinct simian virus in the genus Respirovirus within the family Paramyxoviridae (2, 7). We obtained SA10 from the ATCC and determined a complete consensus sequence for the genome using standard procedures (9). The genome of SA10 was determined to be 15,462 nucleotides (nt) in length (GenBank accession number {type:entrez-nucleotide,attrs:{text:HM583801,term_id:312618595,term_text:HM583801}}HM583801), which is identical to that of human parainfluenza virus type 3 (HPIV3). Comparison with full-length genome sequences of other members of the family Paramyxoviridae showed that SA10 clustered with HPIV3. The extent of nucleotide sequence difference between SA10 and the various strains of HPIV3 is the same as that between the HPIV3 strains (Table ​(Table11). TABLE 1. Nucleotide sequence identity among the complete genome sequences of the indicated viruses The general features of the genome of SA10 (Fig. ​(Fig.1a)1a) are identical to those of the genome of HPIV3. Like HPIV3, the P gene of SA10 contains an additional open reading frame (ORF) encoding the accessory C protein and a putative RNA editing site, 2498UUUUUUCCCCC2508, that is identical in position and sequence to that of HPIV3 (3). Like HPIV3, the insertion of two G residues at this site by the RNA editing mechanism would cause a frameshift and create an ORF encoding a D protein. FIG. 1. SA10 genome map and phylogeny. (a) The genome of SA10 is shown in 3′-to-5′ orientation. The six genes are identified by their encoded proteins. The nucleotide length of each gene is shown above the map, as well as the amino acid length(s) ... Furthermore, SA10 is identical to HPIV3 with regard to the nucleotide lengths of all of the genes, the exact spacing of each gene within the genome and within the respective hexamer subunits (8), and the lengths of the leader, trailer, and extragenic regions (Fig. ​(Fig.1a).1a). The predicted lengths of the unmodified encoded proteins also are identical to those of various strains of HPIV3, with some heterogeneity in the predicted P and HN protein lengths, whereas the lengths of the other proteins are invariant among the HPIV3 strains and SA10. Analysis using 17 HPIV3 HN protein sequences showed that the SA10 HN protein sequence clustered with those of the HPIV3 strains (Fig. ​(Fig.1b).1b). The cleavage site of SA10 is 104DPRTKR↓F110, which conforms to the furin cleavage site (underlining indicates the basic amino acids in the cleavage site). The veritable identity of SA10 with HPIV3 suggests that SA10, rather than being a simian virus, is a strain of HPIV3. In particular, the few differences that occur between SA10 and various HPIV3 strains are of the same frequency as those occurring among the HPIV3 strains. A more likely possibility is that HPIV3 had been transmitted to the monkey from human handlers. A serologic survey of Indonesian macaques showed that nearly half of the sampled wild adult animals were seropositive for HPIV3, whereas no seropositive animals among the sampled wild infant, juvenile, and subadult animals were observed, implying that transmission can occur frequently, even to wild animals (6). In particular, human respiratory syncytial virus was originally isolated from captive chimpanzees and initially was called “chimpanzee coryza agent” (1) but was quickly recognized as a human pathogen and not a natural pathogen of chimpanzees. The present findings on SA10 clarify the taxonomy of Paramyxoviridae, illustrate that host range identification can be ambiguous, and provide a cautionary tale for hasty virus classification.