Comparative genomics of novel paramyxoviruses

Abstract

Paramyxoviruses infect a wide range of hosts, including mammals, birds, reptiles and fish. There are many important human pathogens like measles virus, animal pathogens like canine distemper virus and zoonotic pathogens like Nipah virus within the family Paramyxoviridae. In my PhD study, analyses were performed using comparative genomic approaches on four species of paramyxoviruses. In the first part of my study, Tailam virus (TlmPV) was investigated. It was found that the genome organization of TlmPV was 3’-N-P/V/C-M-F-SH-TM-G-L-5’, with an additional ORF-X in the G gene. In addition to the highly similar genome organization, TlmPV was shown to be the most closely related to Beilong virus (BeiPV) and J-virus (JPV), in terms of hexamer phase pattern and amino acid identities of different genes. In the second part of my study, investigations on three genomes of feline morbillivirus (FmoPV) showed that FmoPV possessed identical genome organization, highest amino acid identities and was phylogenetically clustered with other morbilliviruses, suggesting FmoPV being a morbillivirus. On the other hand, unique features were found in FmoPV within the genus Morbillivirus. In the P gene, FmoPV has the editing site sequence TTA4G4, which is different from the P gene editing site sequence TTA5G3 in other morbilliviruses. Also, FmoPV has a monobasic cleavage site in F protein, which is different from the multibasic cleavage site in other morbilliviruses. In the third part of my study, the genomic and phylogenetic characteristics supported porcine parainfluenza virus 1 (PPIV-1) to be classified in the genus Respirovirus. Furthermore, since it was found that PPIV-1 was significantly more closely related to human parainfluenza virus 1 (HPIV-1) and Sendai virus (SeV) than other members of Respirovirus, the idea about dividing the genus Respirovirus into two subgroups was also introduced, with PPIV-1, HPIV-1 and SeV being in one subgroup, and the other respiroviruses in another subgroup. In the fourth part of my study, four genomes, two from brown rats and two from black rats, of a virus closely related to BeiPV, a paramyxovirus originally discovered from the laboratory cell line, were sequenced. By comparing the five viral genomes, it was confirmed that the naturally occurring viruses from brown rats and black rats, as well as the virus from cell line belonged to the same species. However, there was a truncation in the attachment protein in the strain from cell line. Additional sequencing on more strains confirmed that the naturally occurring viruses did not have such truncation and possessed only one ORF-X, instead of both ORF-X1 and ORF-X2 as in the cell line strain. The investigation continued by comparing the naturally occurring BeiPV with other paramyxvoviruses. A genus, comprising BeiPV, TlmPV and JPV, with extraordinary large genomes and the unique genome organization 3’-N-P/V/C-M-F-SH-TM-G/X-L-5’ among Paramyxoviridae, was proposed to be named Rodenvirus. From my study, the genomic features of three novel species in Paramyxoviridae, including TlmPV, FmoPV and PPIV-1, were revealed. Also, the naturally occurring BeiPV was shown to be with genome organization matching those of TlmPV and JPV, leading to the characterization of a proposed genus.